anemia monograph
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Our goal...
“Eradicating anemia for safer motherhood & healthier generations”
Bangalore Society of Obstetrics & Gynaecologywww.bsog.in
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BANGALORE SOCIETY OF OBSTETRICS AND GYNAECOLOGY
TEAM BSOG 2007- 2008
Office bearers:
President: Dr. Arulmozhi Ramarajan Hon. Secretary: Dr. Harsha N Biliangady Hon. Treasurer: Dr. Parvati Javali Vice President: Dr. Reeta H Biliangady President Elect: Dr. Susheela Rani B S Hon. Joint Secretary: Dr. Jyothika A Desai
Executive Committee:
Dr. Chandrika M Dr. Devika Gunasheela Dr. Jayanthi T Dr. Lata Venkataram Dr. Malini K V Dr. Nagarathnamma Dr. Parimala Devi Dr. Swetha Arasu Dr. Venkatesh N Dr. Vidya Bhat
Invited members:
Dr. Kamini A RaoDr. Hema Divakar
Co-opted members:
Dr. Prakash K MehtaDr. Sheela V ManeDr. Sita BhatejaDr. Sunanda KulkarniDr. Vaijayanthi N V
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We can make a difference…
In our population, anemia appears to be the rule rather than the exception. No age seems to be
exempt. It cuts lives short. It runs as an undercurrent in many premature deaths. It brings down
an individual's productivity and thereby affects the nation's economy. Most importantly, it is
largely preventable & easily treatable. This is where we can make a difference. By preventing,
treating anemia in one woman, we will be giving that family a healthy mother who will be pivotal
in raising a healthy and happy family.
This monograph on anemia is to help understand the ailment better, to help eradicate it from our
society. It is a small effort to put together important aspects of the disease, its causes, presentation,
diagnosis and management, in a simple fashion to make it a ready reference for the practicing
Obstetricians, Gynecologists and family physicians.
Eminent practitioners and senior teachers have contributed chapters in this monograph. The
pages take us through an overview of the problem, a historical note, its presentation through the
different stages in life, the types of anemia, investigations and management. A write up on the
judicious use of blood and blood products adds color to the book. The case reports from our own
members give a personal and clinical touch to the issue.
I express my deep sense of gratitude to all the authors, who have taken precious time off to add
value to the book. My special thanks are due to Dr. Pankaj Desai and Dr. Kamini A Rao for their
forewords and words of encouragement. I am grateful to my friends Dr. Prakash K Mehta and
Dr. Susheela Rani B S for their help in structuring and editing. I express my sincere thanks to
Dr. Reddy's Labs for bringing out this book.
Dr. Arulmozhi RamarajanPresident, BSOG 2007-08
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FOREWORD
Anemia seems to haunt Indians since mythological days. Pandu the patriarch of the Pandavas
was believed to be suffering from this condition. Traditionally we have been defining anemia as
hemoglobin less than 10 gms%. However, time may have come to review this definition as we
Indians seem to be comfortable at a shade lower of hemoglobin levels. This is not to dilute the
efforts of anemia eradication but putting a poser to research scientists on this matter. Do we
Indian have a tendency to have lower hemoglobin? Well as of now it is anybody's guess. Obstetrics they say is a "bloody" business. Having to face hemorrhage when the mother is already
anemic is like pushing her over the brink from the edge. The traditional definition of hemorrhage
pegging the amount of blood loss at > 500 ml too goes for a toss when you see it in the light of an
anemic mother. Therefore Indian obstetricians wisely define hemorrhage clinically rather than
waiting for the blood loss to go upto 500 ml. In anemic subjects this could be lethal. Understandably, nutritional causes remain in focus in most discussions on anemia. However in
India there are vast belts where non-nutritional anemia too has a firm grip in form of sickle cell
anemia or Thalassemia. Interestingly the distribution of Thalassemia throughout the world
explains mysteries of movements of land masses. The way Thalassemia occurrence is distributed,
it shows that Australia and its nearby areas including Fiji, Papua New Guinea and New Zealand
where all one land mass with Asia. Seismologicaly now thought to be the most stable part of the
earth Australia, was separated from Asia ironically through an earthquake carrying along the
genes of Thalassemia. Thus anemia is not only of interest to doctors but also to geologists!
What was a very popular route of iron administration: I.V. Total dose Iron administration has
thankfully lost its popularity of the 80s. It was very hazardous and life endangering which
looking at the risk-benefit ratio was untenable. It is also interesting to know that any oral iron
preparation if does not produce some amount of gastric side effects, is ineffective. Thus when a
pharmaceutical company tries to sell you an iron preparation with no gastric side-effects, rest
assured it is also ineffective!
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FOGSI philosophy for 2007 is FOGSI Cares 2007. In this FOGSI also cares for anemic adolescents.
So as to catch them young: we at FOGSI are focusing on identification of anemic young girls so
that by the time they approach motherhood they are no more anemic. In this it will be pertinent to
state that one more point where anemic motherhood can be averted is by treating anemia in
women who come for infertility treatment. This is a point where before treating her infertility we
can make her non-anemic so that when she is safe on this count from dangers in child bearing. I commend Bangalore O & G society for taking up this theme in a big way.
Dr. Pankaj DesaiPresidentFederation of Obstetric & Gynecological societies of India
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FOREWORD
Anaemia is a major public health hazard in India affecting all segments of the population in
general and children, women and pregnant women in particular. It is the single most important
cause of maternal morbidity and mortality contributing directly to 20% of maternal deaths and
indirectly to a further 20%. What is doubly distressing is that the most common cause of anaemia
in India is nutritional anaemia. Nutritional deprivation compounded by chronic blood loss due
to hookworm and malarial infestations as well as poor bio availability further enhances the
incidence and severity of anaemia.
In an era of hope kindled by awesome scientific advances, we in India are still battling with the
paradox of high maternal morbidity and mortality - much of it due to anaemia. Reducing the
burden of anaemia is essential to achieve the WHO's Millennium Development Goals relating to
maternal and childhood mortality. According to WHO, the strategy for control of anaemia
includes detection and appropriate management; prophylaxis against parasitic diseases and
supplementation with iron and folic acid; and improved obstetric care and management of
women with severe anaemia. Successful delivery of these cost effective interventions requires
the integrated efforts of several health programs particularly those targeted at pregnant women
and young children and the strengthening of health systems, increased community awareness
and financial investment on the part of the government.
Creating awareness about anaemia should be a major 'thrust issue' for each and every member of
the medical fraternity and this book aims to do just that. This Monograph covers each and every
aspect of the detection, management and prophylaxis of the various types of anaemia. The book
has been written in a lucid language with extensive diagrams, photographs and flow charts to
give clarity to the subject. I must congratulate Dr. Arulmozhi Ramarajan on this superlative
effort which I am sure will soon be an essential not only for physicians but also for medical
students, obstetricians, nurses as well as the paramedical fraternity.
Dr. Kamini A. Rao FOGSI Representative to FIGODirector, Bangalore Assisted Conception Centre
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"It is from numberless diverse acts of courage and
belief that human history is shaped. Each time a man
stands up for an ideal, or acts to improve the lot of
others, or strikes out against injustice, he sends forth a
tiny ripple of hope, and crossing each other from a
million different centers of energy and daring those
ripples build a current which can sweep down the
mightiest walls of oppression and injustice."
- Robert F. Kennedy -
“Eradicationg Anemia: Reaching the Unreached”
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SCIENTIFIC SECTION
CONTENTS
1. Anemia: Issues & Interventions Dr. Arulmozhi Ramarajan
2. Anemia through the ages Dr. Malathi Rao 3. Fetal anemias Dr. Ramamurthy B S 4. Childhood anemia Dr. Christi D Savio
5. Anemia in adolescence Dr. Sheela V Mane
6. Bolt from the blue: Anemia of acute blood loss Dr. Prakash K Mehta 7. Off color @ forty plus Dr. Devika Gunasheela 8. Hereditary anemias Dr. Hema Divakar
9. Acquired hemolytic anemias Dr. Biliangady Harsha N 10. Thalassemia in pregnancy Dr. Narayanan 11. Uncommon causes of anemia Dr. Latha Venkataram
12. Investigations: What, when & why? Dr. Jayanthy T
13. IDA in pregnancy Dr. Jyothika A Desai
14. Eating right – right from now! Dr. Sita Bhateja
15. Mirror, mirror on the wall…. Dr. Susheela Rani B S
16. Refractory anemia in pregnancy Dr. Biliangady Reeta H
17. Hemotherapy in ObG: When, why & how? Dr. Shivaram
18. Anemia in pregnancy - a teaching hospital experience Dr. Malini K V
19. Blood banks in Bangalore Dr. Swetha Arasu & Dr. Teena Thomas
20. Case reports
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ANEMIA: ISSUES & INTERVENTIONS
Dr. Arulmozhi Ramarajan, MBBS, MD, DGO, PGDMLE
Consultant and Head of ObGynChurch of South India Hospital, Bangalore
INTRODUCTION:
Anemia is one of the world's most widespread health problems. It affects more than 2 billion
people worldwide, women and children being more affected. The word “anemia” in Greek
means "without blood." It is the generic name given to a group of disorders characterized by a
quantitative or qualitative deficiency of the circulating erythrocytes. In India, about 52% of the
women of reproductive age & 74% of children are anemic.
In a 2002 report, WHO lists iron deficiency, a major cause of anemia, as one of the top 10 risk
factors in developing countries, for “lost years of healthy life”. Conservative estimates suggest
anemia is the direct cause of 3 to 7 percent of maternal deaths worldwide. Other estimates
suggest it is the direct or indirect cause of 20 to 40 percent of maternal deaths. Reducing the
number of women dying in childbirth by 3/4ths by 2015 is one of the key goals of the Millennium
Declaration of the World Health Organization. This goal was agreed upon by world leaders from
189 countries at the UN Millennium Summit in September 2000. If we should bring down our
maternal mortality and morbidity, we need to tackle anemia on a war footing.
Non Industrialized Countries
Anemia Prevalence (WHO)
Age group Industrialized Countries
20.1% 39.0%Children 0 - 4 years
Children 5 - 14 years
Pregnant women
Women 15 - 59 years
Men 15 - 59 years
Elderly > 60 years
05.9% 48.1%
22.7% 52.0%
10.3% 42.3%
04.3% 30.0%
12.0% 45.2%
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ISSUES:
Anemia has serious negative consequences including increased mortality in women and children,
decreased capacity to learn, and reduced productivity in all individuals. Its devastating effects on
health, physical and mental productivity affect the quality of life and translate into significant
economic losses.
Women are vulnerable to malnutrition and anemia throughout their life cycle for both biological
and social reasons. Anemia begets anemia.
At birth, the hemoglobin level and iron stores depend upon the nutrient inputs from the mother.
A normal weight, full term infant that is born to a healthy mother and gets exclusively breastfed
manages enough iron from its own stores and from breast milk. The stored iron is exhausted in
about six months. Additional iron is then required because the iron content of unfortified
conventional complementary foods is insufficient to meet the high iron requirements of growing
6 to 24 months old infants and children. Infants and children who do not obtain adequate iron will
suffer cognitive impairment that will affect their ability to learn and to perform income earning
tasks later in life. The sad part is that subsequent supplementation of iron cannot correct the
cognitive impairment. Many of the girls who survive under such nutritional stress are stunted,
with little chance of recovery. Anemic children are apathetic and anorexic, do not have energy to
play, and have trouble learning. In societies with gender discrimination, girls face greater degrees
of deprivation in food, education and opportunities to bring out their best.
Adolescence is a period of rapid growth, and the requirements for iron are high. Adolescents are
particularly vulnerable to anemia caused by multiple nutritional deficiencies and helminth
infections. This increased requirement of iron continues throughout the reproductive years
because of menstrual blood loss, the iron demands of the developing fetus, and blood loss during
delivery. Teenage pregnancy is like adding fuel to fire. Anemia in the growing years makes these
Causes of Maternal Death and contribution of 3
Iron Deficiency Anemia (IDA)
Adapted from Khan et al, Lancet April 1 2006
Hemorrhage31%
HypertensiveDisorder 10%Unsafe Abortion
5%
Sepsis 11%
ObstructedLabor 7%
Indirect Causes
14%
HIV 3%
Other DirectCauses 5%
Unclassified6%
Anemia8% Deaths
Associatedwith IDA
22%
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children more susceptible to infections including tuberculosis, malaria and HIV.
Through the reproductive years, women in developing countries are pregnant, lactating or
pregnant and lactating. If they do have a break, it is highly likely that they have abnormal blood
loss during menses. Anemia is the rule rather than exception. Physical work capacity and fitness
are reduced in anemic women because iron is needed by the blood to carry oxygen to the brain
and muscles and by the muscles for normal functioning. Anemic women are more likely to
deliver low birth weight infants. They transfer less iron to their fetuses. And these infants are at
increased risk of becoming iron-depleted in early infancy. Anemic women are more susceptible
to puerperal sepsis.
Women with severe anemia are particularly at risk and have a 3.5 times greater chance of dying
from obstetric complications than women who do not have anemia. Anemia related fatigue also
makes the effort of labor more difficult, thus prolonging labor. Severe anemia can lead to heart
failure at the time of labor and delivery. Although it is currently accepted that only severe anemia
causes maternal mortality, it has been estimated that moderate anemia increases a woman's
chance of dying 1.35 times, making it a risk for maternal mortality. Many more women have mild
to moderate anemia than severe anemia. This emphasizes the importance of preventing and
treating all forms of anemia, as the number of deaths associated with mild to moderate anemia is
potentially greater than the number associated with severe anemia.
Various factors including lack of knowledge and awareness, cultural taboos, incorrect food
practices, infections and infestations, lack of access to services and poverty have contributed to
the continued prevalence of this much treatable disease. Anemia is frequently multifactorial.
While iron deficiency is the most common cause of anemia worldwide, genetic traits, such as
thalassemia and hemoglobinopathy (eg, sickle cell disease, glucose-6-phosphate dehydrogenase
deficiency, hemoglobin E disorder) should also be considered in people of Southeast Asian,
African, and Mediterranean descent. In cases of anemia unresponsive to treatment with iron
supplementation, hemoglobin electrophoresis should be performed once iron stores have been
replenished. Recognition, correct classification (diagnosis) and treatment are of the utmost
importance in the management of anemia.
INTERVENTIONS:
History has it that the Greek physicians equated iron with strength and treated weakness in
patients with water in which old swords had been left to rust. In the 17th century, Thomas
Sydenham used iron and steel filings steeped in Rhenish wine for the treatment of chlorosis, an
old name for iron deficiency anemia.
We are certainly better placed today, when it comes to interventions to eradicate anemia. The
methods are inexpensive and effective. As primary care physicians for women, Obstetricians
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have the means, the potential and a duty to achieve this goal of eradicating anemia. We can make
our women and children stronger and healthier, and this in turn will reflect in the overall growth
and development of the country.
Here's how we can contribute:
General measures:
v Health education to create and enhance anemia-awareness amongst our women, children
and health workers.
v Malaria and hookworm prevention and treatment particularly in endemic areas.
v Periodic iron and folic acid supplementation (60mg of iron and 400µg folic acid for 3 months)
for prepubertal and adolescent girls and for all women of childbearing age, in areas of high
prevalence of anemia.
v Certain drugs can cause megaloblastic anemia. Diphenyl hydantoin, barbiturates and oral
contraceptive agents interfere with folate absorption, and metformin that is widely used in
treating DM and PCOS interferes with B12 absorption. Those on long term therapy with these
drugs must be closely monitored.
In infancy & childhood:
v Delayed cord clamping in newborns has shown to increase their iron stores. However, caution
should be exercised in Rh Negative pregnancies, for fear of Rh isoimmunization and risk of
hemolysis in the neonate.
v Exclusive breastfeeding from within one hour of birth to at least six months of age. Avoidance
of prelacteal feeds is equally important.
v Inculcating good eating habits from a tender age is important.
v Introducing fortified foods is an effective way of preventing and treating deficiency disorders.
v Iron Folic Acid supplements & deworming for school children.
v Ensuring basic education to the girl child and empowering her for the life ahead.
In pregnancy:
v Providing at least 100mgs of iron for 100 days during pregnancy and continuing the same for
at least three months after delivery.
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v Routinely deworming pregnant women in the second or third trimester, or in the post partum
period. This should become as routine as giving tetanus toxoid, and is sure to reap bigger
benefits.
v Making deliveries safer, by reducing blood loss during delivery. Active management of the
third stage, use of prophylactic ergometrine / oxytocin / carboprost and taking care to avoid
traumatic deliveries are direct ways in which we can contribute to improved outcomes.
v Providing safe blood transfusions for women with severe anemia is extremely important and
life saving. In situations where a requirement for transfusion is anticipated, for example in
placenta previa / previous cesarean section / severe anemia / HELLP syndrome, one needs to
be adequately prepared.
In the post partum period:
v Encouraging exclusive breast feeding. This minimizes postpartum bleeding when initiated
within an hour of delivery. Additional benefits include lactational amenorrhoea which is a
saving on menstrual loss. It also contributes to a delay in the return of fertility. Thus even if the
woman has not accepted any specific contraceptive method, she is less likely to become
pregnant during lactation, and less likely to come asking for a termination of pregnancy.
v For those who accept oral contraceptive pills, taking IFA tablets during the “blank” weeks
should be emphasized.
v Injectable progesterone contraception should be promoted, for the added benefit of
amenorrhoea during its period of use.
v Monitoring blood loss in IUCD users is important. It is imperative to advise use of
antifibrinolytic / other styptic medication to reduce blood loss in the initial menstrual cycles.
Little drops of water make a mighty ocean, goes the saying. Let every mother and child count.
Let's do our bit to paint our nation pink.
References:
WHO Fact Sheet No. 276 / Feb 2004.
Khan et al. Lancet April 2006.
WHO The World Health Report: Reducing risks, promoting healthy life. Geneva, 2002.
Khanal P, Walgate R. Nepal deworming program ready to go worldwide. WHO Bulletin, 2002,
80: 423-424.
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National family Health Survey-India (NFHS-II) 1998-99, International Institute of Population
Sciences. Demographic Health Survey, 2000.
Survival for Women and Children (SWACH) Foundation. 1997. Anemia in Pregnant Women and
Adolescent Girls in Rural Areas of Haryana, India. Quarterly Progress Report: April to June 1997.
Awasthi S et al. Effectiveness and cost effectiveness of albendazole in improving nutritional
status of preschool children in urban slums – Indian Pediatrics 2000, 37, 19-29.
Concise hematology by H J Woodliff.
Allen LH (2000) Anemia & Iron Deficiency: Effects on pregnancy outcome. Am. J of clinical
nutrition 71: 1280S – 1284S.
Barbin B J, M Hakimi, D Pelletier (2001) An analysis of anemia & pregnancy – related maternal
mortality. J of nutrition 131: 604S – 615S.
Mahomed K (2000) Iron supplementation in pregnancy (Cochrane Review) in The Cochrane
Library, Issue 3, Oxford Update Software.
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“Anemia through the ages”
Dr. Malathi RaoMBBS. FRCS. FACOG
Manipal North side Hospital Bangalore
What is Anemia?
Anemia is a blood disorder characterized by abnormally low level of RBC in the body. It is
usually a sign of underlying disease.
Historical perspective:
Ancients recognized blood as life giving substance. Hebrews in patriarchal age maintained that
blood was the seat of the soul. In Mosaic Law blood is drained before an animal was prepared as
food (practice still followed by Jews).
Circulation of blood was stated by William Harvey in seventeeth century.
1637 – 80 Jan Swammerdam discovered what he called as “Ruddy globules” by looking at blood
through microscope (obviously RBC).
1739 – 74 – William Hewson who published his opinion posthumously that red cells were
present in such numbers, they have to be important. This earned him the title of “Father of
Hematology”.
In 19th century “Anemia” the word was used clinically to refer to pallor of skin, mucous
membrane etc.
1891 – Ehrlich developed triacd stain which allowed him to classify WBC into a scheme similar to
the one we use today.
1905 Gritav Giemsa found the giemsa stain and in 1906 J.H. Wright found wright stain, both of
which are in use routinely in clinical laboratories.
Era of modern Hematology is considered to have begun at Harvard Medical School with the
work of George Richards Minot and his assistant William Parry Murphy.
In 20th century Hematologists are able to diagnose, classify anemia easier, faster, and cheaper
and techniques are developed for treating them from simple nutritional and drug therapy to
advanced modalities like blood transfusion, bone marrow transplants and recently with stem
cell therapy. From this point the investigation of Anemia revolved around the molecular level.
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Iron deficiency Anemia (IDA)
History: A disease believed to be IDA is described in about 1500 BC in the Egyptian Eber’s
Papyrus. It was termed Chlorosis or green sickness in Medieval Europe and iron salts were used
for treatment in France by mid 17th century. Thomas Sydenham recommended iron salts as
treatment for chlorosis but treatment with iron was controversial until 20th century, when its
mechanism of action was more fully elucidated.
Current concepts: IDA is the most common form of malnutrition in the world and is the eight
leading cause of disease in girls and women in developing world. IDA is highly prevalent among
women of reproductive age in south East Asia – 50-70%, but the prevalence in pregnant women
remains at 63.5%.
Impact on pregnancy: Problem of under nutrition in India generally starts much earlier in life
with gender discrimination, menstrual loss, and socio economic status, multiparity, and late or no
ANC.Even interventions like reducing fertility and iron supplementation during pregnancy will
have beneficial effect but still leave most women iron deficient. Effects on pregnancy – Increased
preterm labor, a 2.6 fold increase in PPH and a 3.1 fold increase in low birth weight babies. All
pregnant women should receive prenatal care along with adequate iron supplementations to
decrease the poor outcome in pregnancy.
Anemia Causes And Types
Sickle cell A
Common Causes
A of acute blood loss
Hemolytic A
Inherited - Hereditary Sphrocytosis
Enzymatic pyruvate kinase
G6PD deficiencyAcquired - Drugs, Auto immune, physical
Agents, Micro angiopathic HA,
Paroxysmal nocturnal hemoglobin urea
Fanconi' A
Thalassemia
Sideroblastic A Iron deficiency A
Aplastic A. Megaloblastic A. Vit B 12 , Folic acid
Pernicious A. 80%, Post surgery,
Non megaloblastic macrocytosis
Anemia of chronic diseases
CancerChronic
InflammationAIDS Liver Disease Kidney Failure
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Megaloblastic Anemia
History:
1880 -Ehrlich distinguished between cells he termed megaloblasts in the blood in Pernicious
anemia from normoblasts.
1887 –Quinckle reported large and irregular red cells.
1921 – Zadek noted megaloblasts in the marrow in real life.
1923 – Naegeti described hyper-segmented netrophils in peripheral blood in PA.
1932 – Tempka and Braun described metamyelocytes in the marrow.
1878 – 1976 – George Hoyt whipple studied the rate of hemoglobin regeneration in dogs made
anaemic by venesection.
1885 – 1950 – George Richard Minot and William Murphy isolated the curative substance as
vitamin B 12. All three shared Nobel Prize in Medicine in 1934.
Causes of Megaloblastic Anemia:
1. Pernicious anemia – 80%
2. Post surgery – gastrectomy and Ileal resection
3. Bacterial overgrowth, parasitic infection
4. Drug therapy
5. Erythroleukemia
6. Hereditary disorders
Causes of Non Megaloblastic anemia: Macrocytosis usually asymptomatic but when associated
with anemia cause wide variety of symptoms.
1.Alcohol abuse and liver disease.
2. Hypothyroidism.
3. Reticulocytosis.
4. Aplastic anaemia
5. Paroxysmal nocturnal haemoglobinurea.
Current concepts: Megaloblastic anemia is always associated with folate and vitamin B 12
deficiency. Caused by slowing of DNA synthesis in all proliferating cells but most apparent in
rapidly growing cells such as haematopoietic precursors. RNA synthesis proceeds normally
leading to larger proportion of cytoplasm compared to the nucleus resulting in megaloblasts.
Etiology of impaired DNA synthesis is due to thymidylase synthetase deficiency because of low
folate and vitamin B12, which reduces tetrahydrofolic acid responsible for thymidylate
production.
Impact on Pregnancy: MA in pregnancy is usually secondary to folate deficiency. Diagnosed in
third trimester or postpartum period because of the adequate storage of folate for upto 20weeks,
which is utilized before anemia becomes apparent.
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Initially increased incidence of spontaneous abortion, abruption placenta and third trimester
bleeding has been reported. However other studies have failed to confirm these findings.
IUGR has been attributed to folate deficiency but is probably due to inadequate placentation.
Embryopathies such as neural tube defects are associated with folate deficiency and
supplementation with folic acid before and in early pregnancy reduces the incidence.
Preventive dose of Folic acid -- 5 mg / day 3 months before pregnancy
Supplementation dose of Folic acid – 4mg / day 3 months before pregnancy
Minimal requirements of vitamin B are necessary for adequate fetal development and serum B 12 12
levels are usually higher in infants than their mothers accounting for lack of significant
deleterious effects on fetus in mothers with PA. Some have described deficiency syndrome in
breast fed neonates of mothers with B deficiency characterized by failure to thrive, 12
developmental regression, and anemia apparent at 6 moments of age.
Sickle cell anemia
Sickle cell anemia is the first genetic disorder whose molecular basis was identified.
History: Known to the people of Africa for hundred of years.
1910 – James B Henick noted sickle shaped RBC in a patient from West Indies.
1922 – Vernon Mason named the disease as sickle cell disease.
1927 – Hahn and Gilespie showed sickling of RBC was related to low oxygen tension.
1940 – Sherman, a student from John Hopkins noted low oxygen altered the structure of
Hemoglobin.
1948 – Jenet Watson showed paucity of sickle cells in peripheral blood of newborn and stated that
it was due to fetal hemoglobin.
1956 – Vernon Ingram and J.A. Hurst sequenced sickle cell hemoglobin and identified glutamic
acid at position 6 was replaced by valine thus diagnosing the molecular basis of the disease.
1995 – Hydroxyurea the first and only drug proven to prevent complications of the disease was
reported by multicentric study.
1984 – The first bone marrow transplant in a child with sickle cell disease was reported and the
cure of the disease was published.
Current concepts: Sickle cell syndromes are autosomal recessive inherited disorders that result
from production of structurally abnormal â chain of adult hemoglobin molecule. Hemoglobin S
the defect occurs at 6th position of â chain where valine is substituted for glutamic acid.
Hemoglobin C lysine is substituted for glutamic acid at 6th position.
Impact on pregnancy: Exacerbations of disease.
Vaso occlusive crisis – more common.
More prone to pyelonephritis.
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Predisposes to symptomatic cholelitheasis and preeclampsia.
Increase in maternal and fetal mortality and morbidity.
Before 1970 fetal loss rate was 80% and maternal mortality was 30 – 40%
Today maternal mortality reduced to less than 1% with aggressive prenatal care, effective
management and intervention in pregnancy.
Hemolytic anemia
History: 1871 – Vanlair and Massius first described Hereditary Spherocytosis.
Current concepts: Hemolytic anemia ( HA) is characterized by an increased rate of erythrocyte
destruction. This premature destruction occurs due to 2 causes
1. Intrinsic defect – Inherited disorders and require molecular diagnosis.
a. Hereditary Spherocytosis – Inherited as autosomal dominant transfer and
occurs due to anomaly of RBC membrane.
b. Enzymatic defect –
i. Pyruvate Kinase Deficiency. Mutation involves structural gene coding for
L type pyruvate kinase.( Embden Meyerhoff pathway)
ii. G6PD deficiency – (Phosphate pathway). X linked disorder. Fully expressed in
heterozygous males. In females enzyme activity may be normal, moderately
reduced or deficient.
2. Acquired HA. :
a. Micro angiopathic hemolytic anemia. – Preeclampsia, HELLP syndrome, HUS.
b. Paroxysmal nocturnal haemoglobinuria.
c. Auto immune hemolytic anemia.
d. Physical agents – thermal injury, physical agents like prosthetic valves, drugs.
Impact on pregnancy: Hereditary spherocytosis in pregnancy is rare. Aplastic or hemolytic crisis
may be the first manifestation of the disease in pregnancy. Folic acid requirements are increased.
When fetus is affected with hereditary spherocytosis jaundice may be more prominent in
newborn, requiring exchange transfusion.
Pyruvate kinase deficiency – Limited data is available in literature but well tolerated in
pregnancy. In the fetus it can cause NON IMMUNE HYDROPS.
G6PD deficiency – Variable effects in pregnancy. Increased incidence of spontaneous abortion,
stillbirth, LBW, neonatal jaundice, and non immune hydrops are reported.
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Aplastic Anemia
Current concepts: Etiology is unknown in many cases. Rare and acquired disease usually due to
bone marrow failure secondary to physical, chemical, infectious insults, or nutritional deficiency.
Diagnosis depends on laboratory evaluation, bone marrow biopsy and peripheral blood
examination.
Introduction of bone marrow transplant as treatment in1969 by Thomas et all have changed the
life expectancy of these patients.30 years ago 1in 10 patients survived for 1 year and now 7 out of
10 survive and are restored to a quality of life.
Thalassemia in pregnancy
Current concepts: Thalassemia syndromes are inherited disorders that result from decreased
synthesis of â or á globin chain leading to reduced hemoglobin concentration.
Impact on pregnancy: Women with Thalassemia major both â and á rarely live to become
pregnant. Obstetric focus is prenatal diagnosis and recognition of carrier state in couples.
Prenatal diagnosis is possible by obtaining fetal cells for DNA analysis.
Replacement of blood and blood components in obstetrics.
Storage and transfusion of sterile compatible blood or blood constituents is a routine and life
saving procedure in obstetrics.
Key developments: 200AD – Reports of mystical qualities of blood is noted.
1667 - Richard Lower – reported first heterologous blood transfusion from lamb to an insane man.
1818- James Blundell initiated first human-to-human blood transfusion in acute hemorrhage due
to PPH.
1900 – Karl Landsteiner defined the blood groups and donor and recipient could be precisely
matched.
1914 – Hustin added citrate to prevent clotting.
1937 – First blood bank was established in Cook county hospital, U.S.A.
Bone marrow transfusion:
Century ago bone marrow was administered by mouth to patients with anemia and leukemia.
1950 – Early attempts were made with several transplants in France following radiation
accident.
1958 – Jean Dausset described human histocompatibility antigens.
1968 – First successful Bone marrow transplant was done at the university of Minnesota, U.S.A.
The recipient was a child with severe combined Immunodeficiency and the donor was a
sibling.
1973 – Physicians at Sloane Kettering cancer institute N.Y. performed unrelated bone marrow
20
transplant in-patient with Combined Immune deficiency syndrome and after 7th time
engraftment was achieved and hematological function became normal
1970 – First patient with acute Leukemia was treated with unrelated bone marrow transplant
with success.
1980 – Various individual registries of HLA typed people were established.
1986 – national bone marrow donor registry began operations in U.S.A.
1990 – Dr. E. Donnall Thomas was awarded the Nobel Prize in Medicine for his pioneer work in
transplantation.
Today Bone marrow transplant is used in many hematological diseases notably in Leukemia and
Aplastic Anemia.
Stem cell therapy: Several types of stem cells have been discovered from germ cells, the embryo,
fetus, and adults. Each of these has the potential to revolutionaries the future of regenerative
Medicine in cell replacement therapy and to treat a variety of debilitating diseases. Stem cell is a
cell with the ability to divide indefinitely in culture and with the potential to give rise to mature
specialized cell types. Stem cells can be embryonic origin or adult stem cells found in diverse
tissues and organs. The best-studied adult stem cell is the haematopoietic stem cell ( HSC), which
have been used in clinical settings for over 40 years and form the basis of Bone marrow transplant
success. Umbilical cord blood contains a rich source of HSC that can be used to reconstitute the
blood system and can easily be extracted and cryopreserved, thus allowing HLA typed stem cell
banks to be established.
Marrow and Cord blood transplantation technology continue to evolve and has the potential
for use in Medical therapy of numerous life threatening diseases.
References:
Medline search
Clinical Obstetrics and Gynecology- September 1995, volume 38, number 3
Williams Obstetrics
21
Foetal Anaemia
Dr. B.S.Rama Murthy MD DMRD DNB
Consultant Radiologist,
Srinivasa Ultrasound Scanning Centre Bangalore
Anaemia is defined as a pathological deficiency of the oxygen carrying component of blood
measured in unit volume concentration of Haemoglobin (Hb), red blood cell volume or red
blood cell number.
Foetal haemoglobin concentration increases with gestational age (GA). Hence the threshold Hb
concentration value below which foetal anaemia exists varies with gestational age. Multiples of
median enable us to express the level of Hb concentration below which foetal anaemia is
diagnosed.
Mari G and the group of sixteen others classified foetal anaemia as follows:
Mild anaemia – Hb conc. – 0.84 to 0.65 the median for GA
Moderate anaemia – Hb conc. – 0.65 to 0.55 median for GA
Severe anaemia – Hb conc. – less than 0.55 median for GA
Hydrops occurs when the Hb concentration falls below
5 gm/dl which corresponds to 0.46 times the median at 18 weeks and 0.36 times the median at 37
weeks.
Foetal anaemia is caused either by decreased production or increased destruction/loss of red
blood cells.
Decreased production: Congenital eg. Fanconi's pancytopenia, TAR syndrome, Diamond
Blackfan anaemia congenital dyserythropoietic anaemia etc. (marrow hypoplasia syndromes).
Mild anemia
Moderate anemia
Severe anemia
16 18 20 22 24 26 28 30 32 34 36
Gestational Age (Weeks)
1.16
0.84
Median
0.65
0.55
0
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
22
Acquired such as parvovirus B 19 infection.
Increased destruction/loss: Alloimmune anaemia (D, Kell, Kidd, ABO incompatibility),
foetomaternal haemorrhage, donor foetus in twin to twin transfusion sequence.
Haemoglobinopathies which affect the oxygen carrying capacity in the foetus may also be
considered. Alphao thalassemia (Bart's Hb) is an example and results in early foetal hydrops.
In anaemic fetuses the change in haematocrit results in a change in the blood viscosity and in turn
results in impaired release of oxygen to the tissues. Increased cardiac output and vasodilatation
are the main mechanisms by which the foetus attempts to keep metabolic equilibrium.
Diagnosis:
Obstetric history: Blood group and Rh type of mother and father, anti D administration in
previous pregnancies or abortions, previous issues with specific syndromes
It is the history that puts the process of foetal investigation underway. Sometimes ultrasound
detected foetal hydrops may set forth the process of investigation.
Maternal investigation: Relevant maternal investigations include Anti red cell antibody titre
(titres greater than 1 in 16 may prompt foetal testing however it should be pointed out that the
Indirect Coomb's test titres may not correlate with foetal haemoglobin levels), TORCH and
Parvovirus molecular or immunologic testing, Kleihauer Betke testing to recognize and
quantitate foetomaternal haemorrhage.
Foetal non invasive investigation: Ultrasonography:
Includes grey scale and doppler imaging
Grey scale imaging:
= Foetal hepatosplenomegaly reflects extramedullary erythropoiesis. Spleen length
and perimeter nomograms help us in objectifying the diagnosis.
= Small bowel serosal definition reflects presence of very early ascites.
= Bobbing cord sign reflects hyperdynamic circulation.
= Hydrops foetalis – end result of severe anaemia is severe tissue hypoxia / acidemia,
cardiac failure and decreased plasma oncotic pressure.
= Placental thickening, polyhydramnios,
Doppler imaging:
Decreasing Hb levels are associated with rising velocities in foetal circulation. This relation has
been proved in several series. High cardiac output and reduced blood viscosity are the factors
which result in hyperdynamic vascular flow states. Initially intrahepatic umbilical vein and
ductus venosus velocities were studied. We now have a large body of convincing evidence
showing that decreasing Hb concentrations are linearly related to increasing MCA peak systolic
velocities (PSV). MCA has been the chosen vessel because of the ease with which it can be
demonstrated by colour doppler. It's orientation enables one to achieve 0o or as close to 0o
23
doppler angle easily. The point of sampling is just beyond its origin from the internal carotid
artery in the plane of circle of Willis. The mapping is done with colour flow. Spectral doppler is
run for a few seconds only. The interobserver and intraobserver variability is low. Serial MCA
PSV measurements are at weekly intervals beginning from 20 to 22 weeks gestational age. All
fetuses with moderate or severe anaemia have PSV's above the 1.5 MoM's (multiples of median)
for gestational age. When this level of MCA PSV is reached invasive diagnosis and therapy is
planned (cordocentesis and intrauterine transfusion). Foetuses with below 1.5 MoM's MCA PSV
have no anaemia or mild anaemia (which anyway does not need transfusion). The 1.5 MoM cut
off has a sensitivity of 88% and specificity of 87% for moderate to severe anaemia. With the
advent of MCA PSV surveillance amniotic fluid spectrophotometry is almost totally given up.
Amniocentesis and Liley curve has a sensitivity of 76%.
The correlation between foetal Hct and MCA PSV is excellent not only for alloimmune anaemia
but also for anaemia due to other causes. MCA PSV surveillance has made it possible to avoid
70% of invasive procedures.
Furthermore the MCA PSV drops when anaemia is corrected.
Foetal invasive investigation:
Amniocentesis: Spectrophotometry (OD change at 450 nm)
Foetal blood sampling: Hb%, Reticulocyte count, Hct, Blood group and Rh type, Direct Coomb's
test, Bilirubin levels.
Therapy:
Congenital causes of marrow failure cannot be treated in the true sense of the term. Causes of
foetal anaemia due to acquired causes like alloimmunisation, Parvovirus infection or
foetomaternal haemorrhage can be managed by intrauterine transfusion until sufficient foetal
16 18 20 22 24 26 28 30 32 34 36
Gestational Age (Weeks)
0
10
20
30
40
50
60
70
80
90
100
1.50 Multiples of the medianMedian
24
maturity is attained. Delivery and neonatal management is then planned.
Since intrauterine transfusion (intravenous or intraperitoneal) is the bedrock of treatment we
shall now go through a few relevant details. Foetal transfusion is needed in only 10% of at risk
fetuses (Rh incompatibility) for severe anaemia before 34 weeks, the remaining 90% have mild or
no anaemia and can be managed with MCA PSV surveillance. With widespread usage of anti D,
the incidence of moderate and severe foetal anaemia has fallen. Even so alloimmune anaemia
due to Rh incompatibility is still the single largest cause.
Counselling: The parents should be counseled regarding the process of treatment, the number of
sittings that may be needed and the need for weekly monitoring of MCA PSV post procedure.
The possible complications during foetal transfusions should be highlighted. Informed consent
is taken.
Indication: Moderate / severe foetal anaemia as defined by the nomogram referred to above.
Foetal hydrops has lower salvage rates.
Preparation: The probe is sterile draped, the abdomen is surgically prepared and draped. No
maternal premedication is needed. Tocolysis and antibiotics are started on the morning of the
transfusion.
Site of foetal access: The cord insertion into the placenta is affords good access both for blood
sampling as well as transfusion. The intrahepatic umbilical vein may be used if the foetus is
dorsoposterior and the placental insertion site of the cord is difficult to access.
Foetal Hb concentration is estimated while the needle is in situ and if anaemia is moderate or
severe transfusion is done via the same needle. The pretransfusion foetal blood sample is also
subjected to Hct, reticulocyte count, direct Coomb's test and bilirubin estimation.
Donor unit: O-ve, packed red cells with a haematocrit of at least 85%, washed and irradiated (100
ml). Cross matching with maternal blood is recommended.
Foetal paralysis: Is achieved by Pancuronium 0.25 mg/kg estimated foetal weight injected IM
into the foetal thigh.
Volume transfused: Is computed using the donor haematocrit, foetal haematocrit and the
foetoplacental blood volume for gestational age. Aliquots of 10 ml are injected into the umbilical
vein through the needle coupled to a three way.
Continuous turbulence is observed in the umbilical vein during the intravenous injection. A
check is maintained on the foetal heart rate.
At the end of transfusing the desired volume a post procedure foetal blood sample is obtained
before withdrawing the needle. Hb, and HCt are obtained.
20 to 30 ml of the donor unit is also transfused into the foetal peritoneum at the end of the
intravenous transfusion.
Post procedure : Foetal MCA PSV is recorded to demonstrate a drop in velocities. Weekly MCA
25
PSV surveillance is done and the subsequent transfusion is planned when the MCA PSV again
reaches beyond 1.5 MoM's. This generally occurs about 2 to 3 weeks after a sitting.
Complications: Cord haematoma, foetal exanguination and bradycardia are the complications,
Serial transfusions are done until the gestational age is 34 weeks after which delivery is planned.
Foetal transfusion is not only done for alloimmune anaemia but also for parvovirus B 19 and
foetomaternal haemorrhage as well. The term 'tide over transfusion' is used in these situations.
Thus we see that the causes of foetal anaemia are protean. Recognition of foetal anaemia is based
on history, maternal and foetal investigations. Foetal transfusions have revolutionized the
therapeutic scene.
References:
1. Mari G and the collaborative group for diagnosis of fetal anemia with Doppler
ultrasonography. Noninvasive diagnosis by Doppler ultrasonography of fetal anemia due
to maternal red-cell alloimmunization. N Engl J Med 2000;342:9–14.1.
2. Liley AW. Liquor amnii analysis in the management of pregnancy complicated by rhesus
sensitization. Am J Obstet Gynecol 1961;82:1359–70.
3. Nicolaides KH, Rodeck CH, Mibashan RS, Kemp JR. Have Liley charts outlived their
usefulness? Am J Obstet Gynecol 1986;155:90–4.
4. Fan FC, Chen RYZ, Schuessler GB, Chien S. Effects of hematocrit variations on regional
hemodynamics and oxygen transport in the dog. Am J Physiol 1984;238:H545–52.
5. Harman CR, Bowman JM, Manning FA, Menticoglou SM. Intrauterine transfusion --
intraperitoneal versus intravascular approach: a case-control comparison. Am J Obstet
Gynecol 1990;162:1053-1059.
6. Oepkes D, Seward PG, Vandenbussche FPHA, et al. Doppler ultrasonography versus
amniocentesis to predict fetal anemia. N Engl J Med 2006;354:156-164.
26
Childhood Anemia
Dr. Christi Dominic Savio MD, DCH, Consultant Pediatrician,
Church of South India Hospital, Bangalore
Anemia is one of the commonest problems encountered in pediatric practice with nearly 70 1
million children below the age of 6 years in our country suffering from it. The vast majority of it is 2
due to the dietary deficiency of iron. This is surprising, given the fact that iron deficiency is
eminently amenable to prevention and treatment. What then is the reason for this high
prevalence in this day and age? Is it that we doctors are so busy treating other “more serious”
diseases that we forget or ignore this easily remediable condition? Or perhaps we ignore the fact
that Iron Deficiency Anemia (IDA) can and does take an enormous toll on the health of the
community including causing irreversible and permanent functional damage to the developing
brain. This article is an effort to sensitize us to what has been termed the Tragedy of Iron
Deficiency Anemia during infancy and early childhood.
PRACTICAL DEFINITION OF ANEMIA
The normal Hemoglobin varies with the age and sex of the individual and is given in Table 1
below. Anemia is said to be present when the level of Hemoglobin falls below these levels.
IRON DEFICIENCY AND IRON DEFICIENCY ANEMIA
Iron deficiency is the predominant nutritional deficiency that causes anemia all over the world.
According to the World Health Organization, iron deficiency is the most common and 5
widespread nutritional deficiency in the world.
Relation between Iron Deficiency and Iron Deficiency Anemia
Iron deficiency is defined as a condition in which there are no mobilizable iron stores and in
which signs of compromised supply of iron to tissues, including the erythron, are noted. It is only
TABLE 1: Normal Hemoglobin level
Population Group Normal Hemoglobin (grams per dL)
Adult Male
Adult Female (Non pregnant)
Adult Female (Pregnant)
Children 6 to 59 months of age
Children 5 to 11 years of age
Children 12 to 14 years of age
4Source: World Health Organization
13
12
11
11
11.5
12
27
when there is severe iron deficiency that anemia occurs. In
mild to moderate iron deficiency tissues are functionally
impaired though there is no anemia. It is important to realize
that iron deficiency causes impairment of cellular
functions even at levels that do not cause anemia
Prevalence of Iron Deficiency Anemia (IDA)
Iron deficiency is the only micronutrient deficiency that is
prevalent in significant numbers in both the developed and
the developing countries. WHO estimates that 2.1 billion 6
people globally are affected with anemia mainly because of iron deficiency. This is 30 percent of
the total world population!
1The prevalence of IDA in India based on various studies is as follows
However findings of the DLHS - RCH (District Level Household Survey under Reproductive and
Child health programme) jointly done by Ministry of Health and Family Welfare and 7
Department of Women and Child Development in 2002-2003 has put the figures of anemia
prevalence much higher as follows –
This is an alarming situation which is worsened by the fact that many among the health
profession are blissfully ignorant of the gravity of this problem!
TABLE 2: Prevalence of Anemia in various population groups
7TABLE 3: Prevalence of Anemia in various population groups (DLHS – RCH Report)
Total Population
Iron Deficiency
Iron Deficiency Anemia
Anemia
Venn Diagram showing relationship between Iron Deficiency and Anemia
Population Group
Infants and toddlers
Children 1 to 6 yrs
Adolescent girls
Non-pregnant women
65
60
88 (3.3% had severe anemia)
56.4
Pregnant women
Lactating women
74
85 (9.9% had severe anemia)
Prevalence (percentage)
Population Group
Children less than 5 years
Children 5 to 10 yrs
Teenagers 10 to 19 years
65
92
86
Prevalence (percentage)
28
Groups at greatest risk for developing IDA are
v Children of all ages, particularly those between the ages of 6 months and 5years
v Preterm infants
v Women at the time of puberty, pregnancy and lactation
v The lower socioeconomic groups
v Non- meat eating groups
v Those with diseases like recurrent malaria, hook-worm infestation, and amebiasis.
Consequences of Iron Deficiency
It is vital for us to remember that anemia is only one of the consequences (although the most
visible one) of iron deficiency. Following are some of the important effects of iron deficiency.
1. Effects on the developing Central Nervous System (CNS)
This is one of the most disastrous consequences of Iron deficiency. Iron deficiency
results in impaired cognitive performance, diminished IQ, overall decrease in
scholastic performance and behavioral abnormalities including Attention Deficit
Disorder (ADD). The tragedy of this is that the deleterious effects of iron deficiency on
the cognitive performance in infancy and childhood are not correctable by subsequent 8-11
iron therapy. In other words the impairment in cognitive performance is
irreversible. Thus prevention of iron deficiency is the only way to prevent CNS
impairments.
2. Effects of Iron Deficiency on Scholastic Achievement in older children
Iron deficiency results in poor learning ability even among older children and
adolescents. Numerous studies have demonstrated poor learning scores in older
children and adolescents with iron deficiency including those with iron deficiency 12, 13
without anemia.
3. Compromised cardiovascular response to physical exercise
The cardiovascular response to physical exercise is compromised in children with
nutritional anemia even when it is mild and hence these children may never attain their 14
full potential in various school activities.
4. Impaired Immune Status
Iron deficiency causes increased mortality and morbidity from infections in all age
groups. This is because iron deficiency results in impaired intracellular killing in the
leucocytes, decreased ability of the lymphocytes to replicate and lowered concentration 15
of cells responsible for Cell Mediated Immunity. In one study in India it was found that
anemic children were 5.75 times more susceptible to Lower Respiratory Infections
compared with their non-anemic counterparts. The authors concluded that prevention 16
of anemia will reduce the incidence of LRTI.
29
5. Suboptimal utilization of energy sources by the muscle cells.
Iron deficiency causes impaired work performance in adults and adolescents with even
mild iron deficiency without anemia.
6. Breath-holding Spells:
Iron deficiency is implicated in the causation of breath-holding spells in infants and
young children. Iron supplementation results in decrease in the frequency of breath-17-19
holding spells.
7. Increased risk of Febrile Seizures:
Studies show that children with iron deficiency have a greater chance of having febrile 20-22
seizures than their non iron-deficient counterparts.
8. Heart and Lung Disease:
Ischemic Heart Disease and symptoms of Chronic Lung Disease are worsened by iron
deficiency.
9. Cold Intolerance:
Chronic iron deficiency causes cold intolerance in one-fifths of the patients by interfering
with thyroxin and catecholamine metabolism. This may manifest as neuralgia, tingling
and numbness and vasomotor disturbances.
10. Increased heavy metal absorption:
Divalent metals like zinc and cadmium are absorbed excessively in the presence of iron 23, 24
deficiency leading to their toxicity.
11. Pseudotumour Cerebri:
Iron deficiency is one of the causes of this condition also known as Benign Intracranial
Hypertension.
12. Iron deficiency in Pregnancy:
Iron deficiency increases the maternal mortality and morbidity, perinatal mortality and
prematurity. Infants of iron deficient mothers develop anemia earlier and require more
iron than that available in breast-milk.
Iron Absorption
The absorption of iron from the gut depends upon various parameters of which the following are
of clinical importance having therapeutic implications
1. Forms of Iron
Iron is available as a) Heme and b) Non-heme forms. The latter in turn can be either
ferrous (divalent) or ferric (trivalent)
Heme iron is absorbed from the gut as intact metalloprotein and is not chelated by
dietary factors like phytin and tannins. It may thus appear to be the ideal form of iron for
supplementation. However, free heme in the gut rapidly polymerizes itself and becomes 30
unavailable for absorption. Therefore, free heme is not the ideal form of iron for
pharmacological use.
The ferrous and ferric forms of iron have different absorption pathways, namely the
Divalent metal transporter 1 (DMT1) pathway for the ferrous form and the Beta 3
Integrin and the Mobilferrin pathways for the ferric form.
2. Inhibitors of Iron Absorption
Many factors that are commonly found in the diet are potent inhibitors of iron
absorption. Some of the common inhibitors are phytates (present in cereals, legumes,
nuts and seeds), calcium (found in milk and milk products) and tannins (present in tea,
coffee and cocoa).
3. Enhancers of Iron Absorption.
Hemoglobin iron present in the meat and poultry, Vitamin C found in fruits, juices,
potatoes and vegetables such as green leaves, cauliflower and cabbage and condiments
such as Soya sauce enhance the absorption of iron several fold.
Knowledge of these modifiers of iron absorption is useful for the clinician who can make
appropriate adjustments in the patients' diet while on medicinal iron.
Diagnosis of Anemia
For practical purposes anemia is classified as mild when the hemoglobin is 10 and above,
moderate when it is between 7 and 9.9, severe when it is below 7 and very severe when it is below
4 (all values expressed as grams per dL).
1. Clinical examination
25-27.Clinical Examination is not very reliable for the diagnosis of anemia. Sensitivity of diagnosing
anemia is only 66 percent when the hemoglobin is in the range of 5 to 8 grams and 93 percent when
it is below 5 g / dL.25 Examination of palm for pallor is more reliable in children because of the 26
frequency of conjunctivitis in this age group.
2. Investigations
Since the clinical examination is not very reliable, investigations are essential to confirm and
quantify the anemia.
a. Hematological Tests
These are the basic tests required to diagnose anemia and include Hemoglobin
estimation, peripheral blood smear, and reticulocyte count. However, as already
mentioned, anemia is a rather late manifestation of iron deficiency and therefore other
tests are essential to diagnose iron deficiency in the early stages.
b. Tests to diagnose Iron deficiency:
The important tests that are used to diagnose iron deficiency are Serum Iron, Serum
Ferritin, Serum Transferrin (Total Iron Binding Capacity) and Serum Transferrin
31
receptor level.
i. Serum Ferritin:
41This is the best single test for diagnosing iron deficiency . The only disadvantage is that
Ferritin is an acute phase reactant and therefore is elevated in chronic inflammatory
states. Thus, while a low serum ferritin level is diagnostic of iron deficiency a normal
level in the presence of chronic inflammation does not exclude iron deficiency. A level 2
less than 15 ìg per liter is diagnostic of iron deficiency.
ii. Serum Transferrin Receptor levels (sTfR)
This is a relatively new test and therefore not widely available. It is as sensitive as Serum 2,
Ferritin levels and it has the advantage of not being affected by chronic inflammation. 28-32
The normal range is 3-9 mg/L. In iron deficiency s TfR is elevated to above 9 mg/L
A practical and inexpensive method of diagnosing iron deficiency is to assess the
response to iron therapy. Iron deficiency is confirmed if the Hb rises by 1 g/dL or the
Hematocrit rises by 3% following a 4 week course of iron therapy in the dose of 3 33
mg/kg/day of elemental iron.
Another useful test to diagnose IDA in its early stages is the Red Cell Distribution Width
(RDW). This is an index of the variation of red cell size and can detect subtle degrees of
anisocytosis. Thus, elevated RDW is the earliest sign of IDA and is more sensitive than a 34
peripheral blood smear in the diagnosis of IDA. It is also more sensitive than serum
iron, ferritin or Total Iron Binding Capacity (TIBC). The normal range of RDW is 11.5 to
14.5
Treatment
Any underlying cause for the iron deficiency like occult bleeding, worm infestation should be identified and treated.
Iron therapyIron is available as various compounds. The compound of choice is ferrous sulfate because of its
42proven track record in terms of safety, efficacy and their low cost.
The dose is 6 mg of elemental iron per kilogram body weight per day. (WHO, however,
TABLE 4: Severity of Anemia
Severity
Mild
Moderate
Severe
10 and above
7 to 9.9
Below 7
Hemoglobin (g /dL)
Very Severe Below 4
32
4recommends 3 mg instead of 6 mg ). Iron therapy should be continued for a few months after the hemoglobin has increased to acceptable levels in order to build up adequate stores in the body.
The percentage of elemental iron in various salts is given in the following table.
Newer Iron Preparations
Many newer forms of iron preparation are now available in the market with claims about their superiority. However none of these have been found to be superior to ferrous sulfate in terms of
42cost effectiveness. The following are some of the newer preparations.
a. Iron Hydroxide Polymaltose. This preparation made a huge splash when it was launched and it was claimed to be superior to the older preparations!35 But several studies both in India and abroad have concluded that this compound is inferior to Ferrous Sulfate. A few studies have even found it to be totally
36-38ineffective.
b. Carbonyl Iron. It is said to be very safe. Side effects are very minimal and the liquid preparation does not stain the teeth (The last mentioned may be a consideration particularly among children of the higher socioeconomic group). It is as effective as ferrous sulfate. The greatest advantage is its safety profile. Doses as high as 1000 to 10,000 mg have been tolerated without side effects in non-anemic and anemic adult volunteers and risk of iron poisoning in children
39,40can be eliminated by its use.
c. Sodium Iron EDTA. It is very safe and effective. It is not affected by the presence of iron absorption inhibitors like phytates and tannins in the diet. It is particularly
43, 44useful in food fortification.
d. Iron Ascorbate: Safe and effective.
As mentioned early an effort must be made to identify the cause of the iron deficiency such as helminthiasis, chronic malaria, and occult gastrointestinal bleeding like Meckel's Diverticulum and appropriate treatment instituted.
TABLE 5: Percentage of Elemental Iron in the commonly available preparations
Preparation
Anhydrous Ferrous Sulfate
Crystalline Ferrous Sulfate (7 H O)2
Ferrous Fumarate
Ferrous Gluconate
37
50
Ferrous Succinate
Colloidal Iron
12
Percentage of Elemental Iron
20
33
23
33
Prevention of Iron Deficiency
Since the effects of iron deficiency, particularly those on the developing brain, in young children are irreversible it is vital that iron deficiency be prevented at all cost. Prevention of iron deficiency is fairly easy if the doctor is sensitized to the issue. The following are the groups that should be targeted for preventive measures.
* In communities where prevalence of iron deficiency is 40 percent or more 4
Tips for preventing IDA in infants and toddlers
v Encourage breast feeding for at least 1 year
v Use iron containing weaning food
v Do not use unmodified cow's milk for infants less under 1 year of age
v Encourage the use of iron rich vegetables like green leafy vegetables, beans, peas
v Promote use of meat wherever it is acceptable.
Eating practices that promote iron absorption from gut
v Do not drink coffee, tea at meal-time. Tea drinking to be postponed to 2 hours after meals
v Use milk, cheese and other dairy products as between-meal snack rather than at
mealtime.
Key Points
v Iron deficiency (ID) is a universal problem in children and women of child-bearing age.
v ID is a systemic disease and not merely a hematological disease.
v Impairment of cellular functions occurs in iron deficiency even when there is no anemia.
v ID can cause irreversible cognitive and learning disabilities with an overall reduction in
the IQ.
v All children and women in the reproductive age group require prophylactic low dose
medicinal iron to prevent iron deficiency.
4TABLE 5: Groups to be targeted for Iron supplementation to prevent IDA
Population group Dosage Schedule Duration of Supplementaion
Low Birth Weight Infants 2 to 23 months of age
2 mg / kg / day2 months to 23 months of age
Normal Infants 6 to 23 months of age *
2 mg / kg / day 6 months 23 months of age
Children 24 to 59 months of age * 2 mg / kg / day up to 30 mg 3 months
School Aged children * (above 60 months age)
Iron: 30 mg / dayFolic Acid: 250 :g / day
3 months
All women of child bearing age *
Iron: 60 mg / dayFolic Acid: 400 :g / day
3 months
Pregnant and Lactating Women As above Throughout pregnancy
34
References
1. Deeksha Kapur et al. Nutritional Anemia and its Control. Indian J Pediatr 2002;69 (7):607-
616
2. WHO 1968. Nuritional Anemias: report of a WHO scientific Group, WHO, Geneva,
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3. George Buchanan. The tragedy of iron deficiency during infancy and early childhood. J
Pediatr 1999;135:413-5
4. Iron Deficiency Anemia – Assessment, Prevention and Control – A guide for program
managers. UNICEF, UNU, WHO 2001.
5. DeMaeyer EM, Adiels-Tegman M. The prevalence of anemia in the world. World Health Stat
Q 1985; 38:302-316.
6. Draper, A. (1997) Child development and iron deficiency. The Oxford Brief, pp.1–6. INACG
(International Nutritional Anemia Consultative Group), Washington,DC
7. Indian Medical Association 2006. http://www.imanational.com/Anaemia.htm#
8. Lozoff et al. Iron deficiency anemia and iron therapy effects on infant developmental test
performance. Pediatrics 1987; 79(6):981-95
9. Lozoff et al. Abnormal behavior and low developmental test scores in iron-deficient anemic
infants. J Dev Behav Pediatr 1985; 6(2):69-75
10. Walter T. Infancy: mental and motor development. Am J Clin Nutr. 1989;50(3 Suppl:655-61
11. Lozoff et al. Long-term developmental outcome of infants with iron deficiency. N Eng J Med.
1991;325(10):687-94
12. Halterman et al. Iron Deficiency and Cognitive Achievement among school-aged children
and adolescents. Pediatrics 2001;107:1381-1386
13. Sen and Kanani. Deleterious functional impact of anemia on young adolescent school girls.
Indian Pediatr 2006; 43(3):219-226
14. Mani et al. Cardiovascular Response in Anemia. Indian J of Pediatr 2005; 72:297-300
15. Mullick et al. Impact of iron deficiency anaemia on T lymphocytes & their subsets in children.
Indian J Med Res. 2006 Dec;124(6):647-54
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547-550.
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An analysis of 50 cases. Indian Pediatr 1990; 27: 1073-1079.
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20. Daoud et al. Iron status: A possible risk factor for the first febrile seizure. Epilepsia 2002;
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35. Langstaff RJ et al. Treatment of iron deficiency anemia: a lower incidence of adverse effects
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38. BC Mehta. Iron Hydroxide Polymaltose : Iatrogenic Cause of Persistent Iron Deficiency
Anaemia Despite Continuous Oral Iron Therapy; J Assoc Physicians India.
2002 Feb;50:279-80
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40. VR Gordeuk et al. High-dose carbonyl iron for iron deficiency anemia: a randomized double-
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41. Assessing the Iron Status of Populations. Report of Joint World Health Organization /
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42. Technical Consultation on Strategies for prevention and control of iron deficiency anemia
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43. Bothwell TH. Iron fortification with special reference to the role of iron EDTA. Arch
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Asia Pac J Clin Nutr 2002; 11(2):123-7
37
Anemia in Adolescents
Dr. Sheela V. ManeConsultant
Anugraha HospitalBhagwan Mahaveer Jain Hospital Bangalore
Adolescence is a significant period for physical growth and sexual maturation. Nutrition being
an important determinant of physical growth of adolescents, is an important area that needs
attention. More than two thirds of the adolescent girls suffer from anemia. Anemic adolescent
mothers are at a higher risk of miscarriages, maternal mortality and giving birth to stillborn and
underweight babies. Anemia in children and adolescents is often not a well appreciated and
recognized problem, but is an important impediment to physical and cognitive development.
The most common anemia in adolescents is that due to iron deficiency. 30-90% of adolescent
children in India are anemic depending upon socio-economic condition and whether they are
from rural or urban area. Basal requirement of iron during this period is 3mg/kg/day in female
taking into account both basal, and menstrual loss together. The cumulative effect of continuing
high iron needs and tendency of young women to eat less than men, probably explains why the
prevalence of I.D.A among females appears to increase through out adolescence. In females the
increase in the iron need is distributed over a longer period than in male. Girls have their growth
peak earlier than boys at mean age of 11.5 years of age with 95% from 9.7 to 13.3years. Tanner
stage 2 to 5 begins a year before peak growth and continues for a total of about 4 years, with
menstruation typically starting about 1 year after peak growth. There is a higher requirement of
iron for the female as compared to male during adolescent period and reproductive age period
due to blood loss during menstruation, pregnancy and lactation. Iron loss during menstruation is
estimated to be 16mg/kg/day.The overall iron requirement increases from a pre-adolescent level
of 0.7-0.9 mg/day, to as much as 2.2 mg/day or perhaps more in heavily menstruating young
women. The mean requirement for absorbed iron reaches to about 1.5mg/day at peak growth.
Hence adolescents girls are unlikely to acquire substantial iron stores during this period because
intake may average as little as 10-11 mg iron/day. The low iron store during this period in these
young women of reproductive age will make them susceptible to I.D.A during pregnancy
because dietary intake alone is insufficient in most cases to meet the requirement of pregnancy.
The importance of nutritious diet during this period in a woman's life cannot be overemphasized.
There are certain factors which contribute to dietary imbalances in this period.
38
Factors influencing nutrition of adolescents
Common factors
1. Conditioning factors
v Infectious diseases are important factors responsible for malnutrition, particularly in
children and adolescents. Diarrhoea, intestinal parasites malaria and tuberculosis all
contribute to malnutrition.
v Poor environmental sanitation also leads to repeated bouts of infections.
v Girls lose a considerable amount of iron (average 1 mg daily) during menstruation.
Therefore, they require additional iron rich foods and supplements.
2. Cultural factors
v Food habits, customs, beliefs, traditions and attitudes.
v Religion
v Food fads
v Cooking practices
v Social customs
3. Socio-economic factors
Malnutrition and anemia are largely a by-product of poverty, ignorance, insufficient education,
lack of knowledge regarding nutritive value of foods, large family size, etc.
4. Gender issues
Girls and young women are discriminated against in both quantity and quality of food. On top of
this, they are married early and suffer early pregnancy and child birth further compromising
their nutritional status.
Factors specific to adolescents
Adolescents have a world of their own and have different eating patterns that influence their
nutrition. Adolescence is a period of emergence of an individual into a more independent phase
of life, which influences food behavior also. There is a lack of a sense of urgency regarding future
health. Family meals become less important. They tend to break away from family eating patterns
and succumb to unbalanced diets under influence of peers, mass media.
Personal self esteem and body image guide the eating behavior. Missing meals especially
breakfast is extremely common. SHAHN Survey-2002 among Delhi school students, reveals that
30% boys and 40% girls skip one meal everyday and breakfast is the commonest casualty (54%).
So how can one address this problem in the adolescents?
39
Role at community level
Healthcare providers must educate the community to provide education on importance of
adolescent nutrition and influence the adverse socio-cultural practices.
Education regarding balanced diet for both boys and girls:
v provide education on the importance of nutrition for adolescents themselves and on
their offsprings
v promote good food selection and safe cooking practices
v promote concept of kitchen garden where green leafy vegetables etc. can be grown at a
very low cost
v create awareness in community to factors contributing to malnutrition and nutritional
anaemia, especially in girls.
v Involve other functionaries like AWW, schoolteachers, ASHAs to identify and tackle
nutritional problem.
v create awareness in community about role of malaria and hookworm infestation in
causing and aggravating anaemia
Role of individual counseling
Following tips can be used for counseling parents
v Food should be attractively served, with variety in colour, shape, size and texture.
v Likes and dislikes of the adolescent should be kept in mind
v Impress upon them that the growing bodies of the adolescents need balanced and
wholesome diet, missing meals is deleterious for health and breakfast is very important
for a good beginning of the day
v Snacks should be wholesome and nutritious
v Most of whole pulses should be included in diet
v Occasional consumption of ̀ junk food`may be allowed
v Highly fatty foods should be avoided
v Adolescent should be encouraged to exercise their choice and responsibility of foods
v The diets of girls need special emphasis on iron rich food, like leafy vegetables whole
gram cereals, dry fruit, egg, jaggery etc. The iron requirement is high because of
menstrual losses and growing phase.
Food fads, and anemia in adolescent children
Adolescents are more likely to skip meals at home,eat irregularly,make excessive use of less
nutritious snack food (junk foods). Young women often eat less than dictated by their appetite,
out of fear of obesity.
40
Basic approach to prevention of IDA includes:
Education to increase dietary iron intake. Fortification of staple food with iron and introduction
of iron containing food in the diet
Control of infection, worm infestation.
Pharmacological iron supplementation.
Food fortification is one of the most effective ways of prevention of iron deficiency. Fortification
of suitable food vehicles with absorbable forms of iron is a highly desirable approach in
controlling iron deficiency.
Iron supplementation is essential for the rapid treatment of severe iron deficiency anemia as well
as for prophylaxis and prevention of anemia in both sex and age groups. Supplementation with
oral iron tablet or syrup is the most widely used approach to control global problem of iron
deficiency anemia.
Under adolescent girls' scheme, it is proposed to provide 100mg of elemental iron daily to all
adolescent girls every year for 100 days. Addition of 25mg of vit C to iron folate tablet has shown a
higher Hb response as compared to iron folate tablet alone in adolescent girls. The most common
form of iron in iron tablet is ferrous sulfate (20%iron) although fumarate (33%iron) and gluconate
(20%iron) are some times used. Based on a recent multicentric study in India it is now
recommended that adolescent girls on attaining menarche should be given weekly dosage of the
IFA tablet containing 100mg elemental iron and 500ug folic acid once a week accompanied by
appropriate dietary supplementation.
References :
ARSH WHO Module
Bhave's 'TEXT BOOK OF ADOLESCENT MEDICINE'
vUndernutrition in adolescence has long-term effects on their productivity
vMalnutrition in adolescence has serious implications with regard to predilection for degenerative diseases in adult life as well as for the health of next generation
vChronic energy deficiency and stunting is common but severe malnutrition is rare
vSubclinical micronutrient deficiencies are common because of increased requirements. Iron deficiency is the most common deficiency. Other common nutrient deficiencies include that of vit A, folic acid, iodine, zinc and calcium. Deficiency of iodine and folic acid in pregnant adolescent can cause irreparable damage to fetus.
vMalnutrition and micronutrient deficiencies are more common in poor socio-economic strata and among pregnant adolescents.
vPrinciples of management of severe malnutrition are similar to young children.
Key Points
41
Bolt from the BlueAnemia due to Obstetric Hemorrhage
Dr. Prakash K. Mehta Chief, Division of Maternal Fetal Medicine
Bhagwan Mahaveer Jain HospitalAsha Pregnancy Care centre, Bangalore.
Introduction:Obstetric Hemorrhage is the most common cause of acute anemia as well as maternal death .It is
estimated that one woman dies every 4 minutes due to this catastrophe. In addition to death,
serious morbidity may follow hemorrhage. Sequelae include adult respiratory distress syndrome,
coagulopathy, shock, loss of fertility, and pituitary necrosis (Sheehan syndrome).
Causes:
Massive obstetric hemorrhage may be antepartum or postpartum
Antepartum Hemorrhage
Early Pregnancy: Causes of hemorrhage in early pregnancy may be abortion, ectopic or molar
pregnancy.
Late pregnancy: If bleeding occurs in later pregnancy or during labor but before delivery,
placenta previa, abruptio placentae or ruptured uterus have to be suspected
Placenta Previa : It occurs in one in every 200 pregnant women, most often in the third trimester.
The classic presentation of placenta previa is painless vaginal bleeding and a soft, non tender
uterus. All patients with placenta previa should be informed of the risk of severe PPH, including
the possible need for transfusion and hysterectomy. Blood may distend the uterus and prevent
effective contraction
Placenta accreta. This is a rare disorder, occurring in only 1 in 5000 pregnancies. 9 to 10% of cases
of placenta previa are associated with placenta accreta, an abnormally firm attachment of the
placenta to the wall of the uterus. This condition most commonly occurs in women who have had
previous uterine surgery. Placenta accreta prevents the placenta from separating from the uterine
wall at the time of delivery and can cause severe bleeding that often necessitates hysterectomy.
Placental abruption. Since ultrasound examination has a high false-negative rate in diagnosing
abruption, this obstetric complication is diagnosed clinically The management of abruptio
placentae is primarily supportive and entails both aggressive hydration and monitoring of
maternal and fetal well-being. Coagulation studies should be performed, and fibrinogen and D
dimer or fibrin degradation products should be measured to screen for disseminated
intravascular coagulation. Packed red blood cells should be typed and held. If the fetus appears
viable but compromised, urgent cesarean delivery should be considered.
Bleeding begets bleeding
42
Uterine rupture. In women who have had a previous Caesarean birth, a disruption of the surgical
scar in the uterus is a rare but dangerous cause of vaginal bleeding, intense abdominal pain and
abdominal tenderness. The presentation of uterine rupture may be similar to that of abruptio
placentae. Treatment includes aggressive resuscitation and urgent surgical delivery.
Others: .Cervical varix during pregnancy is a rare condition. The conventional approach to
cervical varices during pregnancy is expectant management and bed rest. The placement of a
cerclage may result in absence of vaginal bleeding during pregnancy. Ectopic deciduosis is
usually no more than a pathologic curiosity. In a pregnant patient with spontaneous
intraperitoneal hemorrhage, however, it must be considered because it results in a high incidence
of maternal and neonatal mortality.
Postpartum Hemorrhage
The average blood loss at the time of delivery is approximately 500 ml during a vaginal delivery
and 1,000 ml during a cesarean section. Excessive blood loss or "postpartum hemorrhage"
complicates approximately 4% of vaginal deliveries and 6-7% of cesarean sections. Estimates of
blood loss at delivery are subjective and generally inaccurate. Studies have suggested that
caregivers consistently underestimate actual blood loss. Another consideration is the differing
capacities of individual patients to cope with blood loss. A healthy woman has a 30-50% increase
in blood volume in a normal singleton pregnancy and is much more tolerant of blood loss than a
woman who has preexisting anemia, an underlying cardiac condition, or a volume-contracted
condition secondary to dehydration or preeclampsia. Lack of experienced obstetricians, blood
transfusion services, anesthetic services, and operating capabilities also play a role for the less
favorable outcome of PPH.
Risk Factors include PPH in a previous pregnancy, retained placenta, failure to progress during
the second stage of labor, placenta accreta, lacerations, instrumental delivery, large for
gestational age, over distension of the uterus, hypertensive disorders and induction of labor and
augmentation of labor with oxytocin
Causes: The causes for PPH can be remembered by mnemonic “4 Ts”: tone, tissue, trauma, and
thrombosis (Society of Obstetricians and Gynecologists of Canada, 2002).
Tone: Uterine atony is the commonest cause for PPH and account for 90% of cases. Uterine atony
and failure of contraction and retraction of myometrial muscle fibers can lead to rapid and severe
hemorrhage and hypovolemic shock.
Tissue: The placenta is more likely to be retained at extreme preterm gestations (especially <24
wk), and significant bleeding can occur. Retention of a portion of the placenta is more common if
the placenta has developed with a succenturiate or accessory lobe. Failure of complete separation
of the placenta occurs in placenta accreta and its variants.
43
Trauma: Damage to the genital tract may occur spontaneously or through manipulations used to
deliver the baby. Continuing hemorrhage in a patient with a firm uterine fundus may indicate a
hidden vaginal or cervical laceration. This type of injury is easier to identify and repair with
adequate lighting, exposure and assistance. Uterine rupture can occur with previous cesarean
delivery scars. Any uterus that has undergone a procedure resulting in a total or thick partial
disruption of the uterine wall should be considered at risk for rupture in a future pregnancy. This
includes myomectomy; uteroplasty for congenital abnormality; cornual or cervical ectopic
resection; and perforation of the uterus during dilatation, curettage, biopsy, hysteroscopy,
laparoscopy, or intrauterine contraceptive device placement. Trauma may occur following very
prolonged or vigorous labor, especially if the patient has relative or absolute cephalopelvic
disproportion and the uterus has been stimulated with oxytocin or prostaglandins Trauma also
may occur following extra uterine or intrauterine manipulation of the fetus. The highest risk is
probably associated with internal version and extraction of a second twin; however, uterine
rupture may also occur secondary to external version. Finally, trauma may result secondary to
attempts to remove a retained placenta manually or with instrumentation. While puerperal
hematomas typically cause a vulvar or vaginal mass, an occult retroperitoneal hematoma can
present with severe abdominal pain and shock after delivery. Visible hematomas that are less
than 4 cm in size and not expanding may be managed with ice packs and observation. Larger or
expanding hematomas must be incised, irrigated and packed, with ligation of any obvious
bleeding vessels
Thrombosis: If uterine exploration is non diagnostic and the fundus is firm, rarer causes of
hemorrhage should be considered. If venipuncture sites are oozing, coagulopathy should be
considered. Thrombocytopenia may be related to preexisting disease, such as idiopathic
thrombocytopenic purpura, or acquired secondary to HELLP syndrome (hemolysis, elevated
liver enzymes, and low platelet count), abruptio placentae, disseminated intravascular
coagulation (DIC), or sepsis. Rarely, functional abnormalities of platelets may also occur. Most of
these are preexisting, although sometimes previously undiagnosed. . Finally, dilutional
coagulopathy may occur following massive PPH and resuscitation with crystalloid and packed
red blood cells (PRBCs).
Management:
General:
v Accurate estimation of blood loss
v Prompt recognition and treatment of clotting disorders
v Multidisciplinary approach
v Use of adequately sized intravenous cannula
v Importance of monitoring central venous pressure.
v Arrangement of adequate quantity of blood
44
Protocol :
v Assessment - Gathering information
v Diagnosis - Interpreting the information
v Planning - Developing the care plan
v Intervention - Implementing the care plan
v Evaluation - Evaluating the care plan
As with any emergency, the assessment of obstetric hemorrhage begins with the ABCs (airway,
breathing and circulation). A delay in the correction of hypovolemia, diagnosis and treatment of
defective coagulation and/or surgical control of bleeding are the avoidable factors in most
maternal deaths caused by hemorrhage. The main goal is to maintain effective circulating
intravascular volume by prompt and adequate replacement of blood, crystalloids or fresh-frozen
plasma through more than one intravenous line (it might be necessary to pump blood under
pressure) with constant monitoring of the pulse rate and the arterial blood pressure. The rapid
correction of hypovolemia with crystalloids and red cells is the first priority, followed by blood
component therapy.
Lab Studies:
Once the diagnosis of PPH has been made, a CBC and baseline coagulation studies should be
performed.
Initially, the hemoglobin value does not reflect the amount of blood loss. Initial coagulation study
findings are usually within reference ranges; however, abnormalities may be noted. This is most
common when PPH is preceded by abruptio placenta, HELLP syndrome, and fatty liver of
pregnancy, intrauterine fetal demise, embolic events, or septicemia.
If the International Normalized Ratio and/or activated partial thromboplastin time are elevated,
the use of fibrinogen, a thrombin time measurement, D-dimers, and a blood film should be
considered. In late pregnancy, fibrinogen levels are 2-3 times the upper reference range limit in
the nonpregnant state, and a level within the nonpregnant reference range should be viewed with
caution if the clinical picture suggests coagulopathy.
Imaging Studies: The onset of PPH is generally rapid. With proper diagnosis and treatment,
resolution usually occurs before further laboratory work or imaging can be undertaken. In
experienced hands, bedside ultrasound may help reveal clots or retained products; however, the
treatment of PPH includes manual exploration if bleeding persists. This renders ultrasound
redundant in the acute setting at a time when treatment must not be delayed. Antenatal
ultrasound is indispensable for detecting high-risk patients with predisposing factors for PPH,
Continuous slow bleeding or sudden bleeding is an emergency Intervene early & aggressively
45
such as placenta previa, and is becoming increasingly sensitive and specific in the diagnosis of
placenta accreta and its variants
Treatment : When uterine atony is the cause of postpartum hemorrhage, treatment is fundal
massage and uterotonics which could be 10 U of oxytocin in 500 mL of intravenous fluid by
continuous drip, 200-250 mcg of ergonovine intramuscularly, or 250 mcg of 15-methyl
prostaglandin F2-alpha intramuscularly.. Modern management of atonic PPH entails the use of
prostaglandins administered parenterally, orally, rectally, or vaginally. Each has advantages and
disadvantages in terms of efficiency, availability, cost, stability, and ease of administration. The
use of misoprostol and a long-acting oxytocin analogue (carbetocin) is being studied for this use
If the placenta has been delivered, inspection findings suggest whether portions of it have been
retained. If it is undelivered or if retained clots or placental fragments are distending the uterus
and bleeding is persisting despite appropriate ongoing treatment, manual exploration and
removal should be undertaken. This is simultaneously therapeutic by emptying the uterus and
permitting contraction while also aiding in the diagnosis of placenta accreta and uterine rupture.
Cervical and vaginal lacerations may also be palpated at this time.
In addition to the appropriate use of oxytocic agents for uterine atony, surgical techniques,
including uterine tamponade, major vessel ligation, compression sutures, and hysterectomy,
may be required. All gynecologists should be able to perform without delay the operative
maneuvers which are necessary to control the bleeding, including hypogastric artery ligation, or
even emergency hysterectomy. Bimanual compression, uterine packing, and such surgical
interventions as B-Lynch suture, ligation of uterine artery, ovarian artery, and internal iliac artery,
and embolization are effective methods for controlling intractable hemorrhage.
Uterine Tamponade: Attempting to compress the uterine sinuses and to stop bleeding via uterine
packing is a reasonable option for management of PPH. A good packing technique entails careful
layering of the ribbon gauze pack to occlude the whole space of the uterine cavity, which is much
easier in theory than in practice. Sengstaken-Blakemore tube and a Rusch urologic hydrostatic
balloon catheter have been used for this purpose. An inexpensive and easily available alternative
is to use an inflated condom as a tamponade. With aseptic precautions, a sterile rubber catheter
fitted with a condom is introduced into the uterus. The condom is inflated with 250-500 mL
normal saline according to need.
The condom catheter was kept for 24-48 hours, depending upon the initial intensity of blood loss,
and gradually deflated when bleeding ceased
Ligation techniques: Ligation of the uterine arteries, ovarian arteries and hypogastric arteries
will usually control uterine bleeding and arterial embolization is also effective. Uterine artery
ligation. When medical management fails, this is a highly effective option. Uterine artery ligation
can be effective in 93% of cases, with a 2.2% complication rate. It's a fast procedure, too, taking
46
perhaps 5 minutes for both sides. No. 1 chromic resorbable suture can be used to tie at the level of
the internal os and includes 2-3 cm of myometrium. Ligation of the hypogastric arteries: Specific
information regarding its effectiveness is lacking. In a study this procedure was effective in
controlling bleeding in eight of 19 patients (42%). In these patients, blood loss, operating time,
and intraoperative morbidity was increased when compared with a group of patients
undergoing emergency hysterectomy for obstetric hemorrhage without prior ligation of the
hypogastric arteries, There was also a 10 fold higher urologic injury rate. Ligation of the uterine
arteries or hypogastric arteries may be performed; both operations require laparotomies.
Bilateral hypogastric artery ligation has a success rate ranging from 40 to 100%.In contrast;
uterine artery ligation has been shown to have a success rate of 92% and a complication rate of 1%.
Both these techniques aim to leave the uterus intact and preserve fertility.
Postpartum hemorrhage that cannot be controlled by local measures has traditionally been
managed by bilateral uterine artery or hypogastric artery ligation. These techniques have a high
failure rate, often resulting in hysterectomy. In contrast, endovascular embolization techniques
have a success rate of >90%.Placement and utilization of arterial catheters for uterine artery
embolization is becoming more widespread and new surgical technology such as the argon beam
coagulator seems promising.
Hysterectomy should also be considered in severe cases. A reluctance to proceed with
hysterectomy for obstetric hemorrhage may be a more likely cause of preventable death in
obstetrics than a lack of surgical or medical skills.
Others: The non-pneumatic anti-shock garment (NASG) exerts lower body counter pressure as a
means of returning blood to the central circulation and it tamponades the abdomen and pelvis to
decrease further bleeding
Recombinant factor VIIa (40-90 mcg/kg, a clotting factor used for hemorrhage in patients with
factor deficiencies undergoing testing for hemorrhage from several other sources including
variceal and obstetric) has been reportedly dramatically effective in several case reports and a
case series for PPH refractory to oxytocin.
Data Analysis : The Division of Maternal Fetal Medicine at Bhagwan Mahaveer Jain Hospital is a
referral centre for high risk pregnancies. During the years 2005 -06, there were 41 patients with
massive obstetric hemorrhage requiring intensive care. 9 patients were referred with APH of
which 2 patients with massive DIC and ARF died. 3 of these patients had PPH also. There were 35
patients with postpartum hemorrhage requiring intensive care, of which 4 died. Atonic PPH was
present in 7 patients, while the rest were with background of DIC, HELLP or adherent placenta.
DIC associated with massive hemorrhage was identified in 18 patients .HELLP syndrome
worsening the bleeding was present in 21 patients. Four of the patients had infective hepatitis
leading to PPH while AFNL was identified in 3 patients. Majority of the patients had multiple
associated factors leading to hemorrhage with HELLP and PIH being the commonest. HELLP
47
was unidentified in 10 of the patients. Identification of this disorder and investigations including
hematocrit, platelet count and liver enzymes could have possible led to early intervention and
prevented these catastrophes. Obstetric hysterectomy was required for 6 patients. 3
hysterectomies were done for placenta previa accreta , 2 were for atonic PPH with DIC and one for
rupture uterus. Arterial embolization was considered for 3 patients but either because of
associated factors like massive DIC or constraint of time, alternative management methods were
used. Uterine tamponade with roller gauze packing was done in 11 patients .Packing was done
post C. section in 7 patients. 2 patients had to be packed following vaginal delivery. 2 patients
who continued to bleed even after Ob hysterectomy settled down with packing.. Massive
transfusion was required for 30 patients. Majority of these patients were referred in shock or after
the onset of DIC. Awareness, suspicion and early referral can reduce the morbidity and avert
mortality.
Conclusion:
Life-threatening hemorrhage requiring immediate treatment affects only 1 in 1000 deliveries. It
will therefore occur about four times a year in a large maternity hospital. This is infrequent
enough to make practice drills necessary. With so many treatment options, ultimately the choice
of technique becomes one of individual preference, institutional availability and the individual
clinical scenario. Timely hysterectomy should be performed for signs of refractory bleeding.
Application of medical and surgical principles combined with recent technologic advances will
help the obstetrician avoid disastrous outcomes for both mother and fetus.
Blood Volume Loss
500 -1000 (10 - 15%)
Blood Pressure (systolic)
Symptoms and Signs
Degree of Shock
NormalPalpitations, tachycardia, dizziness
Compensated
1000 -1500 mL (15 - 25%)
Slight fall (80-100 mm Hg)
Weakness, tachycardia, sweating Mild
1500 -2000 (25-35%)
Moderate fall (70-80 mm Hg)
Restlessness, pallor, oliguria Moderate
2000-3000 mL(35-50%)
Marked fall (50-70 mm Hg)
Collapse, air hunger, anuria Severe
Blood loss and effects
Accidental hemorrhage Uterine rupture
48
Adapted from Int J Gynaecol Obstet 1997 May; 57(2): 219-26
Antepartum Vaginal Bleeding
Massive Bleeding
Call for help
Evaluate ABCs (airway, breathing, circulation)
Administer intravenous fluids
Administer supplemental oxygen
Consider transfusion
Consider urgent cesarean delivery
History and physical examination
Fetal monitoring
Normal“bloodyshow”
Severely distressedfetus (especially ifthe bleeding beganabruptly with therupture of membranes)
Uterine pain? Inflamed cervix ormucopurulent
discharge
Routineevaluation
No pain or painonly with
contractions;nontender fundus
Pain betweencontractions ortender fundus
Probable cervicalinfection
Culture and treatas appropriate
Consider uterinerupture (especially
if fundus isexpanding)
Consider abruptioplacenta
Monitor fetusand mother
supportive care
Suspect placentaprevia
Suspect vasaprevia
Immediateultrasound
examination ifavailable
Distressed fetus Death of fetus
Consider urgentcesarean delivery
Vaginal deliveryCesarean deliveryif in labor
Urgent cesarean delivery
Consider urgentlaparotomy
49
Postpartum hemorrhage
Abdominal pain and shock withour
vaginal bleeding(rare)
Oozing fromvenipuncture
sites(rare)
Massive bleeding
Consultation for possible
retroperitonealhematoma
Consider coagulopathyCoagulation studies
Call for help
Evaluate ABCs (airway, breathing, circulation)Administer intravenous fluids
Administer supplemental oxygen
Consider transfusion
Placenta delivered?
No Yes
Manual exploration of uterus Vigorous fundal massageOxytocin, 10 to 30 units administeredrapidly in 1L of intravenous saline
Indistinctcleavage plane
Distinctcleavage plane
Considerplacenta accreta
Manualextraction of
placenta
Firm fundus, still bleeding Soft fundus, still bleeding
Explore for cervical,vaginal or vulvar lesions
Consultation forprobable urgenthysterectomy
Bimanualcompression of
uterus while awaiting help
Vaginal or vulvar hematoma
Vaginal or cervical laceration
No lesions Presumed uterine atony
Continued fundal massageMethylergonovine(Methergine),0.2 mg given intramuscularly(if the the patient does not havehypertension)orCarboprost(Hemabate)250 :g intramuscularly
Manualexploration of uterusRepair
4 cm or largerand expanding
Incise, drain andpack
Up to 4 cmand stable
Ice packs,observe
Retained placentaor clots
Uterine rurpture Uterine inversion Nothing found
Seek consultationRepeat algorithm
ResuscitationReplace uterus
ResuscitationUrgent laparotomy
Remove
50
Bibliography:
1. Alvarez M, Lockwood CJ, Ghidini A: Prophylactic and emergent arterial catheterization for
selective embolization in obstetric hemorrhage. Am J Perinatol 1992 Sep-Nov; 9(5-6): 441-4
2. Bobrowski RA, Jones TB: A thrombogenic uterine pack for postpartum hemorrhage. Obstet
Gynecol 1995 May; 85(5 Pt 2): 836-7.3. Haynes J: Use of recombinant activated factor VII in massive obstetric hemorrhage Int J Obstet
Anesth. 2007 Jan; 16(1):40-49.
4. Dildy GA: Postpartum hemorrhage: new management options. Clin Obstet Gynecol 2002 Jun;
45(2): 330-44
5. Wittich AC, Salminen ER, Hardin EL: Uterine packing in the combined management of
obstetrical hemorrhage. Mil Med 1996 Mar; 161(3): 180-2
6. Hayman RG, Arulkumaran S, Steer PJ. Uterine compression sutures: surgical management of
postpartum hemorrhage. Obstetric Gynecol 2002; 99: 502–6
7. Mason BA. Postpartum haemorrhage and arterial embolization. Curr Opin Obstet Gynecol
1998; 11: 475–9
8. Rizvi F, Mackey R, Barrett T, McKenna P, Geary M, Successful reduction of massive
postpartum hemorrhage by use of guidelines and staff education, BJOJ2004 May;111(5):495-8.
51
OFF COLOUR AFTER FORTY
DR. DEVIKA GUNASHEELA, MRCOG (Lond.),
Fellow of Reproductive Medicine (RGUHS)
Anaemia is one of the most widespread and often neglected disorders. It is the bane of
most underdeveloped countries of the world, and a curse of Indian womanhood. WHO
estimates are that two billion people in the world are anaemic, accounting for 30 % of the
world's population. Anaemia affects 13 % of the population in the developed world and
44 % in the developing world. Amongst the Asian countries, perhaps Bangladesh and
China have a higher incidence of anaemia than India, but Pakistan, Nepal and Sri Lanka
have a lower incidence than India. Whereas the incidence of anaemia ranges between 20
and 30 % in the middle income groups, it is much higher in the lower income groups – 60
% (urban women) and 70 % (rural women). In geographical areas where malaria and
helminthic diseases are endemic, the incidence of anaemia rises to almost 90 %. Anaemia
is three times more prevalent in southern Asian women than in European women. It was
found that anaemia was less prevalent after the menopause in European women but
remained common after the menopause among Indian and Bangladeshi women.
The menopausal transition is continuous and not a snapshot in time. In the absence of
disease, this process involves changes and irregularity of both bleeding and hormone
levels. Irregular bleeding that arises during this period is often subject to medical and
surgical investigations and treatment even though the parameters of what are abnormal
are not well established.
Perimenopause or the recently preferred term The Menopausal Transition (MT) is defined
by the WHO as the period in time beginning 2 – 8 years prior to the Final Menstrual 1
Period (FMP) and lasting upto 12 months after the FMP.
Abnormal uterine bleeding is one of the most common complaints during the 2
perimenopausal transition as cycles become more irregular. It has been estimated that
menstrual irregularity occurs in more than half of all women. Bleeding can be irregular, 3
heavy or prolonged. The differential diagnosis during these years is vast, as anatomic
hormonal, and metaplastic processes have a higher incidence : anovulatory bleeding,
uterine leiomyoma, endometrial polyps, adenomyosis, endometrial hyperplasia or
endometrial carcinoma. Anovulation and uterine fibroids are the most common hormonal
and anatomic causes of abnormal uterine bleeding in the late reproductive age.
52
The subjective self – assessment of uterine bleeding is not at all reliable. 40 % of women
with more than 80 ml of objectively quantified menstrual blood loss (an amount that is
significantly associated with development of anaemia) described their bleeding patterns as
only moderately heavy, whereas 14 % with only 20 ml or less of bleeding found this to be
heavy. Only 60 % of women complaining of menorrhagia actually experienced more than 4
80 ml of menstrual blood loss.
HORMONAL THEORIES :
Many theories have been put forward to explain the hormonal mechanisms responsible
for the vagaries of perimenopausal bleeding. Ample oestrogen levels and prolonged
endometrial stimulation in longer anovulatory cycles may well contribute to the rising
incidence of endometrial hyperplasia and dysfunctional uterine bleeding as women 5
transverse the MT.
ANATOMICAL CAUSES :
Leiomyomata and polyps are common in women over the age of 35 and are accepted
cause of abnormal uterine bleeding. Uterine fibroids have a prevalence rate of about
25% over the general population. Though rarely malignant, leiomyomata have always been
a major contributor to abnormal bleeding or pain and remain the most common diagnosis
associated with hysterectomy. Submucous fibroids seem to have a greater effect on
bleeding patterns than intramural fibroids but both lead to heavy and prolonged bleeding.
DIAGNOSTIC WORKUP :
All complaints of irregularity in bleeding patterns may not warrant investigations. But
prolonged bleeding (lasting more than 10 days) or intermenstrual (non-cyclical) bleeding 6
are not considered normal and deserve workup. Although polyps and fibroids are the
most common anatomical concern one should not overlook the possibility of endometrial
carcinoma in the aging female. The incidence of endometrial carcinoma increases with age
from 30 – 39 year old women with the rate of 2.3 / 100,000 women and in the 1
perimenopausal age group (40 – 49 year old) a further increase to 6.2 / 100,000 women.
The importance of endometrial biopsy cannot be over emphasized for women with
abnormal uterine bleeding during the menopausal transition and also after menopause.
The diagnostic approach to a woman with abnormal perimenopausal bleeding has evolved
over the last century from operating room curettage to outpatient vacuum suction
curettage to eventually the Pipelle plastic catheter. Proponents of the Pipelle catheter cite
that it is relatively comfortable for patients. It is reported to have a sensitivity as high as
97.5 % in detecting endometrial carcinoma, but these biopsies were done on woman with 7
known pathology. Of the patients who have had false negative finding by Pipelle
sampling, the disease was either confined to a polyp or comprised less than 5 % of cavity
53
surface area and therefore was missed.
The noninvasive relatively inexpensive and highly reproducible nature of transvaginal
ultrasound makes it an especially attractive assessment tool to exclude uterine
abnormalities. Significant progress has been made in the evaluation of perimenopausal
women using saline infusion hysterosonography (HSN) to help assess the endometrial 8
cavity for focal lesions.
HYSTEROSCOPY :
Another evaluation that may be helpful in selected cases is hysteroscopy. This allows the
identification of endometrial polyps or submucosal fibroids.
Goldstein1 has presented an algorithm that utilizes trans vaginal ultrasonography and
provides a stepwise approach to working up the perimenopausal patient with abnormal
uterine bleeding. If the baseline ultrasound shows a thin distinct endometrial stripe less
than or equal to 5 mm in width, a diagnosis of dysfunctional uterine bleeding can be
safely made. If the endometrial stripe is thickened to greater than 5 mm or it is difficult to
ascertain the endometrial echo, an HSN is warranted for a uterine evaluation. Based on
the HSN results, a diagnosis of dysfunctional uterine bleeding can be made, an office
endometrial biopsy may need to be taken, or a hysteroscopy with resectoscopic biopsy is
performed for final diagnosis and / or therapy.
MEDICAL MANAGEMENT :
Medical treatment of perimenopausal abnormal uterine bleeding is either hormonal or
surgical depending on the patient's symptoms and diagnosis. As anovulatory bleeding is
one of the most common causes, hormonal therapy is the first approach after intra uterine
pathology has been excluded.
NSAIDs :
These are thought to be menstrual blood loss through the inhibition of endometrial
prostaglandins (PGE2 alpha and PGF2 alpha). Mefanamic acid, Tranexamic acid have been
used with varying degree of success.
HORMONES :
Although progesterone only or estrogen progestin combination treatment of irregular or
dysfunctional bleeding is common, no randomized controlled trials to demonstrate their
efficacy in this setting exist. Progestin only regimens such as medroxyprogesterone acetate
(MPA) have been shown to reduce both the amount and duration of uterine bleeding in
anovulatory women. Specifically, MPA 10 mg per day for 10 to 14 days every month is 9
effective in controlling unpredictable anovulatory bleeding. Progestins are able to induce a
secretory transformation in otherwise estrogen – stimulated proliferative endometrium, and
they are effective in allowing a withdrawal bleed for women with thickened endometrial
54
10linings that are commonly seen in anovulation.
Oral Contraceptives in low – risk premenopausal women with hormone – related symptoms
who are not using any form of contraception, modern low – dose (<35 µg ethinyl estradiol)
oral contraceptives offer many advantages with minimal risk (59). New formulations
contain as little as 20 µg of ethinyl estradiol and 1 mg of norethindrone acetate. In
addition to preventing undesired pregnancies, these formulations are associated with a
high degree of menstrual regularity and can be used to treat symptoms associated with a
high degree of menstrual regularity and can be used to treat symptoms associated with
relative estrogen deficiency. The use of oral contraceptive until menopause has been 11
found to be safe in women with no risk factors for cardiovascular disease. Before
starting the administration of oral contraceptives in this age group, patients should be free
of the following risk factors : hypertension, hypercholesterolemia, cigarette smoking,
previous thromboembolic disorders, cerebral vascular disease, or coronary artery disease.
The levonorgestrel – releasing intrauterine device (IUD) is able to release 20 mcg of
levonorgestrel per day to act locally at the level of the uterus. This system has been
shown to be effective for endometrial protection during estrogen therapy. In patients with
dysfunctional uterine bleeding, this progesterone IUD was found to be equally effective
compared with endometrial resection after a 1 – year follow – up. In a population of
women with menorrhagia, levonogestrel – releasing IUDs compared similarly to 12
hysterectomy but at a significantly lower cost.
SURGICAL METHODS :
Hysrerectomy is the second most common operative procedure after caesarean section
among reproductive aged women. The average age at hysterectomy is 44.5 with same
regional variation. Although it is a very effective surgical procedure, hysterectomy is
associated with a certain degree of morbidity and cost. Prior to recommending a
hysterectomy, an adequate preoperative evaluation must include endometrial sampling
and an adequate trial of hormonal therapy to control the bleeding.
The Maine Women's Health Study analysed close to 600 women with these complaints
and found that patients with abnormal uterine bleeding who were treated initially with
nonsurgical management (cyclic progestins, oral contraceptives, or nonsteroidal anti-
inflammatory medicines) had a statistically significant improvement in symptoms through
one year of follow-up. However, close to 25 % went onto have a hysterectomy after the
year of nonsurgical management and noted highly effective relief and improvement in 13
quality of life as measured by surveys.
ENDOMETRIAL ABLATION :
Surgical alternatives to hysterectomy offer less radical and potentially more cost effective
55
methods to treat menorrhagia. Endometrial ablation using lasers or electro cautery or
thermal balloon ablation has been used and demonstrates an amenorrhoea rate of upto 50
% and patients satisfaction close to 90 %.
A large prospective cohort study noted that 80 % of endometrial ablation patients needed
no further surgery, whereas 9% underwent hysterectomy within 5 years of the initial
procedure.14 However, endometrial ablation offers immediate results and has been shown
to be effective on its own, without the need for pretreatment in a benign setting.
SUMMARY:
The management of benign symptoms, diagnosing and treating serious pathology is a
complex balance when viewed in the light of the vast treatment options available. A
detailed history and appropriate testing remain the principal starting point to providing
better care for a woman during her reproductive aging process.
PERIMENOPAUSAL BLEEDING WORKUP AN ALGORITHM
Abnormal Bleeding
Anovulatory bleeding, Ut. Fibroids, polyps, endometrial hyperplasia, endometrial carcinoma.
Menstrual History Laboratory Work UpHb %, PCB, Complete Haemogram, FSH-E , 2
T , T4 TSH3 ,
Trans Vaginal UltrasoundI Hysterosonography
Endometrial Biopsy (Pipelle)
Simple Hyperplasia or normal Pathology
Tissue Insufficient
Hysteroscopy
Normal
Abnormal
Complex Hyperplasia orMalignancy
Hysteroscopy & Curettage
Non Hormonal / Hormonal Treatment
Repeat Endometrial BiopsyIn 6 months for
Hyperplasia
Simple Hyperplasia
Atypical Hyperplasia orMalignancy
Hysterectomy
56
Bibliography :
1. Akas Jain and Nanette Santoro – Endocrine Mechanisms and Management for
Abnormal Bleeding due to Perimenopausal Changes – Clinical Ostetrics & Gynaecology
– 2005 ; Vol. 1, No. 4, 419 – 435.
2. Brambilla DJ, McKinlay SM, Johannes CB, Defining the perimenopause for application
in epidemiologic investigations. Am J Epidemiol. 1994 ; 140 : 1091 – 1095.
3. William W. Hurd – Menopause – Novaks Gynaecology Text Book – 12th Edition ; Chapter
29 : 981 – 1011.
4. Fraser IS, McCarron G, Markham R. A Preliminary study of factors influencing
perception of menstrual blood loss volume. Am J Obstet Gynaecol. 1984 ; 149 : 788 – 793.
5. Santoro N, Brown JR, Adel T, et al. Characterization of reproductive hormonal
dynamics in the perimenopause, J Clin Endocrinol Metab. 1996 ; 81 : 1495 – 1501.
6. Belsey Em, Pinol AP. Menstrual bleeding patterns in untreated women. Task Force on
Long – Acting Systemic Agents for Fertility Regulation. Contraception. 1997 ; 55 : 57 – 65.
7. Stovall TG, Photopulos GJ, Poston WM, et al. Pipelle endometrial sampling in patients
with known endometrial carcinoma. Obstet Gynaecol. 1991 ; 77 : 954 – 956.
8. Goldstein SR. Use of ultrasonohysterography for triage of perimenopausal patients
with unexplained uterine bleeding. AM J Obstet Gynaecol. 1994 ; 170 : 565 – 570.
9. Jennings JC. Abnormal uterine bleeding Med Clin North Am. 1995 ; 79 : 1357 – 1376.
10. Bishop PM, Cabral de Almeida JC. Treatment of functional menstrual disorders with
norethisterone. Br Med J. 1960 ; 5179 : 1103 – 1105.
11. Marshall LM,. Spiegelman D, Barbieri RL, et al. Variation in the incidence of uterine
leiomyoma among premenopausal women by age and race. Obstet Gynaecol. 1997 ; 90 :
967 – 973,
12. Hurskainen R, Teperi J, Rissanen P, et al. Quality of life and cost-effectiveness of
levonogestrel-releasing intrauterine system versus hysterectomy for treatment of
menorrhagia : a randomized trial. Lancet. 2001 ; 357 : 273 – 277.
13. Carlson KJ, Miller BA, Fowler FJ Jr. The Maine Women's Health Study : I. Outcomes of
hysterectomy. Obstet Gynaecol. 1994 ; 83 : 556 – 565.
14. O'Connor H, Magos A. Endometrial resection for the treatment of menorrhagia. N
Engl J Med. 1996 ; 335 : 151 – 156.
57
HEREDITARY ANEMIAS
Dr. Hema DivakarDivakars speciality hospital Bangalore India
Anemia is the commonest medical disorder in pregnancy having varied incidence, etiology and
degree of severity in different populations with the prevalence ranging between 35 to 75 % in
developing countries. (ref 1, 2).
Anemias can be classified according to clinical, morphologic or etiologic factors and
characteristics. There are advantages to each system and they mesh with each other.
Clinical classification allows the physician to adjust the pace of diagnosis and treatment
according to the severity of the patient's condition.
Morphologic classification, based on examination of peripheral smear, is the most common way
to arrive at a specific diagnosis and a good way to proceed in a cost effective search for the source
of anemia.
Etiologic classification describes hereditary anemias and acquired anemias.
This article will detail the HEREDITARY ANEMIAS. These are due to intrinsic defects in the
erythrocyte membrane, glycolytic pathway, glutathione metabolism or haemoglobin molecule.
Since iron deficiency anemia is the most common, many clinicians would initiate therapy and re-
evaluate in one month.
If anemia fails to improve, a more intensive clinical and laboratory evaluation is justified.
Thalassemia is hereditary condition which can be aggravated by pregnancy.
It results when an insufficient amount of hemoglobin is produced to fill the red blood cells.
The unbalanced synthesis of hemoglobin leads to premature RBC death and results in severe
anemia.
This is being detailed in a separate article.
Sickle cell anemia is a hereditary birth defect. It is a recessive, hereditary, familial hemolytic
anemia where abnormal hemoglobin types (SS or SC) produce recurrent attacks (crisis) of pain
and fever.
In sickle cell disease though, this hemoglobin becomes moon (or sickle) shaped, and cannot fit
through the blood vessels properly.
As a result, people with sickle-cell anemia don't get enough oxygen delivered throughout their
bodies causing extreme fatigue.
58
These sickle-shaped cells can also clog the blood vessels, causing tissue damage, organ failure,
and even death.
Sickle cell anemia is most common among African Americans, with about 2 million African
Americans carrying the sickle cell trait.
People who carry the sickle cell gene but do not have sickle cell anemia are said to have "sickle cell
trait".
If both partners carry sickle cell gene - it is passed on to the child. If only one partner carries the
gene , the offspring will be a carrier. Amniocentesis can be performed between the 14th and 16th
week of pregnancy to determine if the fetus has sickle cell anemia.
Sickle cell symptoms tend to vary from person to person. They also tend to increase in severity as
you age.
Common sickle cell symptoms include:
v pain in the stomach, legs, and arms
v chest pain
v jaundice
v extreme fatigue
v growth problems
v frequent illness and infection
Possible complications include:
v Vision Loss: Sickle-shaped hemoglobin cells can block the tiny blood vessels
surrounding the eyes, causing vision loss.
v Organ Damage: Blocked blood vessels can cut off blood and oxygen supply to key
organs, including the liver, kidney, and spleen.
v Stroke: Blocked blood vessels can prevent oxygen supply to the brain, causing a stroke.
v Acute Chest Syndrome: People with sickle cell anemia are highly susceptible to
infection.
v Acute chest syndrome is similar to pneumonia and can cause fever, pain, and breathing
problems.
Laboratory Studies show reticulocytosis except during aplastic crisis. The peripheral smear
shows sickle cells, holly leaf cells or Howell Jolly bodies. The Hb electrophoresis shows varying
amounts of Hb S and Hb F .
Treatment:
There is no treatment for sickle cell anemia.
59
Common management includes:
v penicillin injections to prevent and fight infections
v pain medications
v folic acid supplements, to help grow new red blood cells
v blood transfusions, to increase the number of healthy red blood cells
v bone marrow transplants to help the body create healthy red blood cells
Transfusions are required to keep the hematocrit level at least 30%. Nagel and co workers (3)
reported that recombinant human erythropoietin can stimulate the F reticulocyte responses
In a randomized trial , Charache and colleges reported that hydroxyurea therapy ameliorated the
clinical course of the disease.(4)
Perrine and collegues reported the response of the patients to infusions of arginine butyrate (5)
A remarkable trial (6) of zinc supplementation in the prevention of vaso-occlusive episodes and a
significant reduction in the infective episodes is encouraging.
Pregnancy outcomes in sickling syndromes are highly variable and needs extensive expertise for
procedures like partial exchange transfusions.
Hb C disease – has Hb C
In the heterozygous state, illness is rare unless associated with sickling.
In the homozygous state, relatively insoluble Hb C crystallsises in the oxy haemoglobin state,
causing the red cells to become rigid.
Fragmentation and loss of membrane material leads to the presence of microspherocytes on the
peripheral smear.
Prenatal diagnosis is needed only if SC disease (sickle and Hb C) is suspected.
Symptoms are rare and maternal and perinatal outcomes are good.
Hb E disease – has Hb E
A specific gene defect in the DNA for Hb E results in abnormal splicing leading to defective chain
synthesis. Hence it resembles thalasemmia intermedia. Hb E trait affects 25 % of Southeast Asian
women (7) and has been reported in 50 % of an isolated population in India.(8) Growth restriction
and fetal wastage can occur in those with homozygous Hb E (9) (10).
Hereditary spherocytosis
Hereditary spherocytosis is the commonest form of haemolytic anaemia seen in northern Europe
and it is important to know that most children who have mild disease, can live a normal life, and
do not require splenectomy.
It is one specific familial hemolytic disorder characterized by marked heterogeneity of clinical
60
features, ranging from an asymptomatic condition to fulminant and extremely serious hemolytic
anemia.
The most common characteristic of hereditary spherocytosis is one structure called the
microspherocyte- the sphere-shaped red blood cell, which is caused by loss of membrane surface
area, and an abnormal osmotic fragility in vitro.
Because the spherocytes have a smaller surface area through which oxygen and carbon dioxide
can be exchanged- they perform adequately to maintain healthy oxygen supplies. However, they
have a high osmotic fragility -when placed into water, they are likely to burst.
Frequency of the condition:
Hereditary spherocytosis is the most common of the hereditary hemolytic anemias among people.
Researches done in the past have proven that, in the United States, the incidence of the disorder is
approximately 1 case in 5000 people.
It is proven that this condition is usually transmitted as an autosomal dominant trait, and the
identification of the disorder in multiple generations of affected families is the rule. An autosomal
recessive. The The disease is also encountered worldwide, but its incidence and prevalence in
other groups are not established clearly.
Anemia or hyperbilirubinemia may be of such magnitude as to require exchange transfusion in
the neonatal period.
Anemia usually is mild to moderate; however, sometimes it is very severe and sometimes it is not
present.
Splenomegaly is the rule, and palpable spleens have been detected in more than 75% of affected
subjects.
Severe hemolytic anemia requires red cell transfusions.
Mechanism of the condition:
The most important thing there is to know about this condition is that the defects in hereditary
spherocytosis are in the red cell membrane.
This is because the proteins essential for the integrityof the membrane structure lie immediately
under the lipid layer.
It is proven that different genes code each of these proteins, thus hereditary spherocytosisis a
heterogeneous disorder..
61
Symptoms of the condition:
Every patient should know that the spleen's hemolysis results directly in varying degrees of
anemia and hyperbilirubinemia.
These two conditions can result in symptoms of:
v Fatigue
v Pallor
v Jaundice
Chronic symptoms include anemia and splenomegaly.
Lab Studies:
The classic laboratory features of this type of anemia include minimal or no anemia,
reticulocytosis, an increased mean corpuscular hemoglobin concentration (MCHC), spherocytes
on the peripheral blood smear, hyperbilirubinemia, and abnormal results on the osmotic fragility
test. Other biochemical changes of hemolysis also are also present, including:
v increased lactate dehydrogenase (LDH)
v increased unconjugated bilirubin
v decreased serum haptoglobin
v an increase in MCHC
The treatment of this type of anemia involves pre-splenectomy care, splenectomy, and post-
splenectomy complications. Problem is that children
with severe hyperbilirubinemia caused by this type of anemia are at risk for kernicterus, and
these infants should be treated with phototherapy and exchange transfusion as clinically
indicated.
Iron supplementation:
Researches are showing that iron supplementation supports the increased production of red
blood cells, but in longstanding cases in which patients have taken supplemental iron or received
numerous blood transfusions; iron overload may be a significant problem, being a potential cause
of cardiomyopathy and liver disease.
The hereditary stomatocytosis syndromes
The hereditary stomatocytosis syndromes and allied disorders are usually transmitted in an
autosomal dominant pattern, although apparently sporadic cases have been reported.
Penetrance is variable, with significant disparity in clinical symptomatology between affected
individuals in the same kindred.
62
Many patients present with hemolytic anemia in the neonatal period, but others are
asymptomatic throughout their lifetime.
Aplastic crises associated with parvovirus and other infections have been reported.
An unusual characteristic of the stomatocytosis syndromes is a predisposition to severe life-
threatening thrombosis after splenectomy.
Enzyme deficiency anemias
G6PD deficiency – X linked recessive trait high prevalence
G6PD is the key enzyme in the hexose mono phosphate shunt.
Lack of G6PD lessens the reducing power of the erythrocyte.producing rigid membranes and
Henz bodies.
Diagnosis is by exclusion
Treatment includes Vit E and Folic acid supplementation.
Prognosis is good.
PK pyruvate kinase defeciancy and G6PI glucose 6 phosphate isomerase deficiencies show
symptoms of anemia, jaundice and splenomegaly.
Fetal hydrops and spontaneous abortions are associated with enzyme deficiency anemia.
Conclusions :
Though iron deficiency anemia is a common problem, there are other non-nutritional anemias
that may be seen.
Some of these may manifest for the first time in pregnancy.
Although these conditions are rare, it is important for the obstetrician to recognize these and
initiate appropriate interventions, if and when required.
References
v Die jamaron FME, Abdulaziz A – Anemia in pregnancy – Int J Glyrol obst -1999
v Shehwartz WJ; Tumanu- Iron Deficiency anemia in pregnancy – Clin .obst Gynecol -1993
v Nagel RL ,Shah M, et al. F reticulocyte response in sickle cell anemia treated with
recombinant human erythropoietin: a double-blind study.Blood-1993
v Charache S, Terrin ML,Moore RD,et al. Effect of hydroxyurea on the frequency of
painful crises in sickle cell anemia. New England J of Medicine-1995
v Perrine SP,Ginder GD,Faller DV,et al.A short –term trial of butyrate to stimulate fetal-
globin-gene expression in the beta-globin disorder. N Eng J Med-1993
63
v Gupa VA,Chaubey SB.Efficacy of Zinc therapy in prevention of crisis in sickle cell
anemia:a double bind ,randomized controlled clinical trial.J Assc Physicians India-1995
v Pravatmuang P,Tilokhus M, Suannum M,Chaipat C.Phitsanulok population:the highest
incidence of hemoglobin E in the northen provinces of Thiland and PND
Counseling.Southeast Asian J Trop Med Public Health-1995
v Deka R,Fertility and hemoglobin genotypes:a population study in upper Assam.Hum
Genet-1981
v Ong HC.Maternal and fetal outcome associated with hemoglobin E trait and hemoglobin
E disease. Obstet Gynecol-1975
v Belgir RS. Reproductive profile of mothersin relation to hemoglobin E genotypes.Indian
J Pediatr_1992
64
ACQUIRED HEMOLYTIC ANEMIAS
Biliangady Harsha N. MDAssociate Professor
Kempegowda Institute of Medical SciencesSonologist 'NORTH STAR' Women's Hospital,
Bangalore
Definition: Hemolytic anemias develop from an increase in the rate of red cell destruction.
The normal life span of red cells is 100 - 120 days; in hemolytic anemias this is shortened by
varying degrees and may be a few days only in severe cases.
Classification: There are two basic causes of red cell destruction
1. Intracorpuscular (Intrinsic) i.e. abnormality of the red cells which results in premature
destruction i.e. if these patients are transfused with normal red cells, the transfused cells,
have a normal life span. The condition is mainly congenital due to an abnormality in the
red cell itself i.e. in the membrane itself.
2. An Extracorpuscular (Extrinsic) i.e. development of an abnormal hemolytic mechanism.
Normal compatible red cells are prematurely hemolysed. Whereas red cells from these
patients when transfused to a normal individual will have a normal life span. In other
words these individuals have normal red cells but have developed an abnormal
hemolytic mechanism i.e. there is an acquired hemolytic process or more accurately an
auto immune acquired hemolytic anemia.
AUTO IMMUNE ACQUIRED HEMOLYTIC ANEMIA (AIHA)
AIHA is a group of disorders due to formation of antibodies against the antigens on the surface of
the patients own red cells, i.e. they act as auto – antibodies. The antibodies are most often IgG or
less often IgM or IgA. Some are known to bind complement also. These auto - antibodies may
form as a result of breakdown of T – cell regulation of B cells with the emergence of a hostile clone
of immunocytes. Or, a change in the structure of the surface antigen on red cell is recognized as
'non self' by the immune system. In reality the pathogenesis of AIHA is not really known. AIHA
is not a rare disorder and occurs in all grades of severity ranging from a chronic mild
asymptomatic condition to a rapidly acutely fatal state.
CLASSIFICATION OF AIHA: AIHA is classified depending upon the
1. The temperature at which the antibody reacts with the red cells into warm and cold
antibody types (table1).
2. According etiology in to idiopathic and secondary types (table2).
Warm AIHA: Seen more frequently in adults than in children and the idiopathic form is seen
more often in women over the age of forty. The most important causes of secondary AIHA are
65
chronic lymphocytic leukemia; malignant lymphoma and systemic lupus erythematosus (SLE).
Some drugs like methyldopa are known to cause secondary AIHA. Its use as an antihypertensive
is now rare but is still popular in the management of pregnancy induced hypertension (PIH).
Clinical Features: An insidious onset with features of anemia is usual. In secondary AIHA the
underlying disease is ongoing at the time of hemolysis. Mild to moderate jaundice is present but is
persistently absent in about 25% of the patients. The spleen is always enlarged and is nearly
always palpable, but rarely beyond the limits of the umbilicus. A very large spleen suggests a
chronic lymphocytic leukemia or malignant lymphoma. Moderate hepatomegaly is present but
lymphnode enlargement does not occur in idiopathic cases though it is a common finding in
secondary AIHA. Hemoglobinuria is occasionally seen. In young children and some adults the
onset is sudden following a minor viral or bacterial infection. Intravascular hemolysis is seen as a
hemoglobinemia and hemoglobinuria; oliguria and anuria are rare. Hemolysis normally stops on
its own and is followed by complete recovery. Death occurs rarely when the condition is severe.
Blood Picture: The typical feature is one of reticulocytosis with spherocytosis and positive direct
antiglobuilin test. Reticulocyte count ranges from 5 – 30 % but can be higher. Rarely reticulocye 1
count may be normal or even reduced in an aplastic crisis . Spherocytosis is present in active
disease as is evidenced by a raised osmotic fragility and if mild this may be the only clue as it is 1
unlikely to appear on a blood film. A mild increase in MCV is common .
Polychromatic macrocytes are prominent in a blood film with a high reticulocyte count.
Leucocytosis is seen in acute severe case, and counts of 20 – 30 x 109/L or more are quite common
in chronic moderate cases the count is often normal or very rarely moderately reduced. Platelet
counts are mostly normal or sometimes low enough to cause purpura. Serum bilirubin is between
17 – 50µmol/L. Erythrocyte sedimentation rate (ESR) is markedly elevated in the active phase
returning to normal during remission. Immunoglobulins are reduced in about 50% of the women
the deficiency being IgA most commonly, but IgG and/or IgM deficiency or deficiency of all three
are also seen. Blood drawn for routine examination shows mild agglutination in the collection o
tube and blood film. This is not prevented by drawing blood into pre warmed syringes at 37 C,
representing red cells coated heavily with incomplete antibody. This should not be mistaken for
the more intense agglutination of Cold Hemagglutinin Disease.
Antibodies on the red cell surface: This is detected by positive direct antiglobulin testing using a
broad - spectrum reagent. Monospecific reagents are more precise and it is found that 56% show a
coating with IgG and complement C3, 35% have IgG alone and IgA and IgM. In SLE the red cell
coating is almost always IgG and complement. With methyldopa induced hemolysis it is IgG 2
alone . It is important to understand that there are numerous causes for a positive direct
antiglobulin test besides AIHA. Methyldopa is an important cause for positive antiglobulin test
even in the absence of active hemolysis.
Diagnosis: Typical findings of hemolytic anemia including jaundice, splenomegaly,
66
reticulocytosis and an increased serum bilirubin with a positive direct antiglobulin test. 25% may
not have jaundice. Bone marrow aspiration or a trephine biopsy is indicated and a careful search
for evidence of leukemia, malignant lymphoma and megaloblastic red cells is made. Tests for SLE
must be conducted, in acute cases. In children viral infections must be ruled out.
Course and Prognosis: The course of the idiopathic form of the disease is variable and forecasting
the outcome is difficult. Most patients respond initially to some form of treatment. In chronic
disease hemolysis may continue for years, the disability depending upon the degree of anemia.
No patient is cured if the antiglobulin test remains positive even if hemoglobin, reticulocyte count
and serum bilirubin have returned to normal. A Mayo Clinic study on survival rates has found 3
91% and 73% at one year and ten years respectively .
Treatment: In most adults and children with severe disease corticosteroids, blood transfusion
and splenectomy form the key to management. Immunosuppression may be necessary for some.
Corticosteroids: Induce prompt remission in about 80% of cases. The dose of prednisone varies
from 60 – 80 mg/day to start with, and 5 – 15 mg/day maintenance to keep the hemoglobin at
11Gm%. Patients requiring more than 15mg of prednisone will be benefited by splenectomy.
Corticosteroid therapy is deemed to have failed if there is no improvement after three weeks of
treatment.
Blood Transfusion: Is not necessary in moderate cases. In severe cases packed red cells are used
to maintain hemoglobin levels and blood volume. The auto - antibodies on the red cell surface
interfere with grouping and cross matching and this must be performed by an experienced 4
transfusion specialist. Guidelines for transfusion in AIHA must be strictly followed .
Splenectomy: Is reserved for
1. Idiopathic cases not responding to adequate treatment with steroids and secondary
AIHA not responding to treatment of the underlying cause.
2. Patients requiring large doses of steroids to maintain adequate hemoglobin levels.
Sometimes complete remission may not be achieved but at least the dose of steroid
required is reduced. It is important to explore the abdomen for accessory spleens and
ovarian dermoids. A histopathological examination of the spleen may be the first clue to
a malignant lymphoma.
Immunosuppressive Therapy: Generally reserved for patients that do not respond to
splenectomy and are requiring high doses of steroids. The drugs used are Azathioprine 2.0 – 2.25
mg daily or Cyclophosphamide 1.5 – 2.0 mg daily. Neutrophil count must be carefully monitored
and long term Azathioprine therapy is sometimes associated with the development of malignant 5
lymphoma . All patients with continuing hemolysis must get 5.0 mg of Folic acid/day.
Treatment for secondary AIHA is as in idiopathic AIHA with concurrent management of the
67
causative disorder. When AIHA develops in a patient with a previous H/O malignant
lymphoma or other neoplasm a thorough check for recurrence must be made.
COLD ANTIBODY AUTO IMMUNE ACQUIRED HEMOLYTIC ANEMIA
oAIHA due to cold antibodies that react with red cells at temperatures less than 37 C, are less
common than the warm antibody type.
Two forms are recognized
1. Cold Hemagglutinin Disease (CHAD) characterized by antibodies that react with red
cells at low temperatures.
2. Paroxysmal Cold Hemoglobinuria (PCH) characterized by episodes of acute hemolysis
due to auto - antibodies that act primarily on red cell lysins at low temperatures.
Both CHAD and PCH can be idiopathic or secondary to an underlying disease.
Cold Hemagglutinin Disease: Idiopathic CHAD is seen in adults over 50 years of age. It is rare in
children with most patients running a chronic course. Unlike warm AIHA, CHAD is equally
distributed between men and women. The secondary form occurs as a rare complication of SLE,
malignant lymphoma and chronic lymphocytic leukemia, or a transient anemia secondary to 6
infectious mononucleosis (Table 2).
Clinical Features: In idiopathic CHAD and in CHAD associated with SLE, malignant lymphoma
or chronic leucocytic leukemia the onset is insidious. Two patterns are seen depending on the
thermal range of the antibodies.
Some experience acute intravascular hemolysis and hemoglobinuria in winter and have normal
hemoglobin in summer. Others are well compensated with mild or moderate chronic hemolytic
anemia which worsens only slightly in winter. Agglutination occurs in the peripheral cooler parts
of the circulation causing varying extents of microvascular obstruction and signs of cold
sensitivity ranging from Raynaud's phenomenon, acrocynosis and rarely peripheral gangrene.
These phenomena are seen most often in winter and are unlikely to be seen in temperate climates.
Very rarely a terminal complication of CHAD can be a malignant lymphoma, but more frequently 7
CHAD develops in patients with pre existing lymphoma .
Post infectious CHAD has an acute onset during the second or third week of infection. Acute
intravascular hemolysis, jaundice and splenomegaly are seen. Cold sensitivity is usually not seen
and hemolysis takes up to 2 – 3 weeks to resolve.
Blood Picture: Picture of anemia with red cell agglutination, reticulocytosis and a positive direct
antiglobulin test. Red cell agglutination is an outstanding feature. This picture is seen on films
prepared from capillary blood or blood collected into an anticoagulant and is often seen
macroscopically in the collection tube. Agglutination can be prevented by using pre warmed
syringes and slides kept at 37oC. Hemoglobin is rarely below 8g/dl. Spherocytosis is less marked
68
than in warm AIHA. Reticulocyte count is only mildly increased. Polychromatic macrocytes and
occasional nucleated red cells are seen. White cell count and platelets are normal. Serum bilirubin
is only mildly raised and plasma hemoglobin appears only during active disease, but
hemosiderin is seen in the urine during both active and quiescent phases. Red cell agglutinates
interfere with the functioning of automated counters giving falsely high MCV. Serum and red cell
folate might be reduced.
Immunology: Most cases of CHAD are caused by an auto - antibody referred to as anti – I. This
anti body reacts with the I antigen found on the red cell surface of all adults but not fetal RBC. This o
is a complete antibody which is inactivated at 37 C but agglutinates red cells with increasing o
strength as the temperature drops towards 4 C. The lytic activity of this antibody is much less
compared to that of the Donath – Landsteiner anti body of paroxysmal hemoglobinuria.
The anti – I antibodies of both idiopathic and secondary CHAD are IgM type with ê light chains.
Serum IgM levels are elevated above 6 g/L and IgG and IgA are normal. The anti – I antibody of
CHAD secondary to mycoplasma infection is also an IgM, but is polyclonal consisting of ê and ë
light chains.
oThe direct anti globulin test is positive if blood is drawn and kept at 37 C and washed in warm
saline before testing. The positive test is due to the presence of complement C3d on the red cell
surface.
Prognosis and Treatment: The idiopathic disease progresses slowly and many patients remain o
relatively well especially when upper thermal ranges of the antibody does not exceed 28 C.
Protection from cold or a shift to temperate climate is often enough. Corticosteroids and
splenectomy are rarely effective. Chlorambucil is useful and reduction of IgM in the serum is seen.
When transfusion is necessary pre warmed concentrated red cells are transfused keeping the
patient warm.
Paroxysmal Cold Hemoglobinuria (PCH): A rare disorder seen as attacks of hemolysis with
hemoglobinuria on exposure to cold. The condition develops due to the development of a cold
auto - antibody with strong lytic activity. The blood shows a characteristic bithermic cold
hemolysin that is demonstrated by the Donath – Landsteiner test.
The principle of the test is that the hemolysin in the patient's blood attaches to sensitized red cells o
when chilled and then hemolysed by complement when warmed to 37 C. This cold hemolysin is a
complement binding IgG antibody having anti – p blood group specificity.
Paroxysmal Nocturnal Hemoglobinuria: This rare disorder is associated with a chronic
hemolytic anemia and intermittent hemoglobinuria. The abnormality is an acquired defect of the
red cell membrane making the cells unusually sensitive to lysis by the complement of normal 8
serum. Three cell lines of red cells have been detected in PNH ; two populations of
intermediate and extreme sensitivity to complement lysis and a third resistant population.
69
Appears usually between 30 – 40 years and affects men and women equally. Hemoglobinuria is
seen in all patients and is related to sleep irrespective of sleeping time. Characteristically night
urine or the first morning sample is colored. Hemosiderinuria is always present and at autopsy
renal tubules are laden with hemosiderin. Red cells are not found in the urine.
Blood picture: Shows anemia of varying intensity. Moderate macrocytosis, polychromasia and
moderate leucopenia are observed. Reticulocytes are increased but not to the expected extent for
the anemia present.
Diagnosis: This is made by the intermittent hemoglobinuria and presence of hemosiderin in
urine. The condition should be suspected in patients with refractory anemia. Showing a
pancytopenia, reticulocytosis or if a H/O transfusion reaction is present.
Treatment: No specific treatment is available; management is mostly supportive with 9
concentrated red cells as transfused red cells have a normal life span. Oxymethalone 10 -50 mg
and androgens can be used. Splenectomy is of no value.
Hemolytic Anemia Due To Drugs and Chemicals: Many drugs cause hemolysis and they fall
into three categories.
1. Those that have a direct toxic action on the red cells, hemolysis is dose related and occurs
in most normal subjects provided that sufficient dose of the drug is administered.
2. Those that cause hemolysis as a result of a hereditary metabolic abnormality of the red
cells.
3. Those that cause hemolysis by an immunological mechanism (Table 3).
TABLE 1. WARM AND COLD ANTIBODIES IN AIHA
WARM COLD AIHA
*CHAD
†PCH
Immunoglobulin Class IgG IgM IgG
Optimal reaction temperature
o37 C
o0 - 4 C
o0 - 4 C
Antibody specificity Often anti Rh Anti - PAnti -I or anti - I
Immunochemical characteristics
Polyclonal Monoclonal Polyclonal
Serological behavior in vitro
Incomplete Agglutinin Bipahsic hemolysin
Protein on red cell IgG 35%IgG +C56%C 9%
C 100% C 100%
Legend: * Cold Hemagglutitnin Disease † Paroxysmal Cold Hemoglobin Uria
70
TABLE : 2 CLASSIFICATION OF AUTO - IMMUNE ACQUIRED HEMOLYTIC ANEMIA
Idiopathic 50%
Secondary 50%
Drugs: Methyldopa, mefenemic acid, L-dopa , procaine amide
Infections: Mycoplasma pneumoniae, infectious mononucleosis, cytomegalovirus.
Chronic lymphocytic leukemia
Malignant lymphomas
Systemic lupus erythematosus
Other autoimmune diseases rheumatoid arthritis, chronic active hepatitis, myasthenia gravis, ulcerative colitis
Miscellaneous - carcinoma, sarcoidosis, ovarian teratoma
TABLE : 3DRUGS AND CHEMICAL AGENTS THAT MAY CAUSE HEMOLYTIC ANEMIA
Drugs that regularly cause hemolytic anemia in normal subjects by direct toxic action
Acetylphenylhydrazine Phenylhydrazine
Arsine Potassium chlorate
Chloramine Resorcinol
Copper Sodium chlorate
Formaldehyde Sulphanilamide
Naphthalene Sulphapyridine
Para aminosalicylic acid Sulphasalazine
Phenacetine Sulphones
Phenazopyridine
71
* In addition to these drugs, many of the agents causing hemolysis in large doses will cause hemolysis in small doses in G6PD defiant patients.
TABLE 3DRUGS AND CHEMICAL AGENTS THAT MAY CAUSE HEMOLYTIC ANEMIA
Drugs that cause hemolytic anemia in subjects with hereditary *
metabolic abnormalities of the red cell ((principally G6PD deficiency)
Analgesics Sulphones
Acetanilide Dapsone, Thiazole sulphone
AntimalarialsPamaquinPentaquinPrimaquin
MiscellaneousAcetyphenylhydrazineMethylene blueNalidixic acidNaphthalelneNiridazolePhenylhydrazine Trinitrotoluene
NitrofuransNitrofurantoin
SulphonamidesSulphacetamideSulmethoxazoleSulphanilamideSulphapyridineSulphasalazine
ImmuneAmidopyridineAntazolineCephalosporinesChlorpropamideCisplatin
SulphasalazineStibophenSulphonamidesTeniposideTetracyclineThiazides
Drugs that cause hemolytic anemia by immune mechanism
DipyroneErthromycinInsulinIsoniazidNomifesinePara aminosalicylic acidParacetamol
* *Thiopentone 13TolbutamideTriamterene
Auto - immuneL - dopaMefenemic acidProcaineamide
PenicillinPhenacitinQuinidineQuinineRifampicin
72
References
1. Liestveld J.L. et al Variability of erythropoietic response in auto immune hemolytic anemia,
Immune Hemolytic Anemia Methods in Hematology; Chaplin H (Ed): 987.
2. Isis .P. Serological diagnosis and characterization of causative antibodies ; Immune
Hemolytic Anemia, Methods in Hematology; Chaplin H (Ed): 1985.
3. Silverstein .M.N et al Idiopathic Acquired Hemolytic Anemia, Survival in 117 cases; Arch Int
Med: 129 (1972).
4. Masouredis . S. P. et al Transfusion Management of auto immune hemolytic anemia,
Immune Hemolytic Anemias Methods in Hematology Volume 12; 1985.
5. Grunwald H.W. et al Acute leukemia and Immunosuppressive drug use, Arch Int Med , 139;
461: 1979.
6. Crisp D & Pruzanski W. B – cell neoplasms with homogeneous cold reacting antibodies (cold
agglutinins); Am J Med 72; 915: 1982.
7. Chaplin H. Lymphoma in primary cold hemagglutinin disease treated with chlorambucil,
Arch Int Med ; 142: 2119 1982.
8. Rosse W.F et al The population of red cells in paroxysmal nocturnal hemoglobinuria of
intermediate sensitivity to complement lysis significance and mechanism of increased
immune lysis Brit J Hemat: 28:181 1974
9. Rosse W.F Treatment of paroxysmal Nocturnal Hemoglobinuria, Blood; 60: 20, 1982.
73
THALASSEMIA AND PREGNANCY
Dr. Narayanan. R. Malathi Memorial Hospital Bangalore
The name thalassemia was coined at the University of Rochester in New York by the Nobel Prize-
winning pathologist George Whipple and the professor of pediatrics William Bradford from the
Greek thalassa for sea and -emia, meaning the blood. Thalassemia means "sea in the blood." But
for the Greeks, the sea was the Mediterranean, so thalassemia also conveys the idea of the
Mediterrranean in the blood.
The reason that the gene for beta thalassemia is relatively common, among people of Italian and
Greek origin is that parts of Italy and Greece were once full of malaria. The presence of
thalassemia minor (like sickle cell trait in Africa) afforded protection against malaria, and
therefore, this gene thrived. In India too, thalassemia is common in areas like the Kutch where
malaria was once endemic.
Thalassemia is the most common autosomal recessive genetic blood disorder that affects the
production of hemoglobin, resulting in anemia. It is estimated that there are 200,000 thalassemics
in the world among whom 5000 to 8000 are in India. About 100,000 babies worldwide are born
with severe forms of thalassemia each year. Thalassemia occurs most frequently in people of
Italian, Greek, Middle Eastern, Southern Asian and African ancestry.
The two main types of thalassemia are called "alpha" and "beta," depending on which part of an
oxygen-carrying protein in the red blood cells is lacking. Both types of thalassemia are inherited
in the same manner. The disease is passed to children by parents who carry the mutated
thalassemia gene. A child who inherits one mutated gene is a carrier, which is sometimes called
"thalassemia trait." Most carriers lead completely normal, healthy lives.
A child who inherits two thalassemia trait genes - one from each parent - will have the disease. A
child of two carriers has a 25 percent chance of receiving two trait genes and developing the
disease, and a 50 percent chance of being a thalassemia carrier. If one of the partners is a carrier the
offspring has no risk of being a thalassemic, but 50% chance of being a carrier (Diagrams).
74
Alpha Thalassemia:
Most individuals with alpha thalassemia have milder forms of the disease, with varying degrees
of anemia. The most severe form of alpha thalassemia, which affects mainly individuals of
Southeast Asian, Chinese and Filipino ancestry, results in fetal or newborn death.
Diagram depicting the transmission of Thalassemic gene to the offspring when both partners are carriers:
T
TN
N N
N
N
T
T
TNTN
25% Thalassemic 50% Carrier 25% Normal
NormalCarrier
Thalassemia
T
---
T N N
TN
50% Carrier
N
TN NN NN
50% Normal
TNNT
NormalCarrier
Thalassemia---
Diagram depicting transmission of Thalassemic gene if one partner is a carrier:
75
Beta Thalassemia:
The most familiar type of thalassemia is beta thalassemia. It involves decreased production of
normal adult hemoglobin (Hb A), the predominant type of hemoglobin which begins soon after
birth and continues until death. The globin part of Hb A has 4 protein sections called polypeptide
chains. Two of these chains are identical and are designated the alpha chains. The other two
chains are also identical to one another but differ from the alpha chains and are termed the beta
chains. In persons with beta thalassemia, there is reduced or absent production of beta globin
chains.
There are two forms of beta thalassemia. They are thalassemia minor and thalassemia major
(which is also called Cooley's anemia).
Thalassemia minor: The individual with thalassemia minor has only one copy of the beta
thalassemia gene (together with one perfectly normal beta-chain gene). The person is said to be
heterozygous for beta thalassemia.
Persons with thalassemia minor have (at most) mild anemia. This situation can very closely
resemble that with mild iron-deficiency anemia. However, persons with thalassemia minor have
a normal blood iron level (unless they are iron deficient for other reasons). No treatment is
necessary for thalassemia minor. In particular, iron is neither necessary nor advised.
Thalassemia major (Cooley's anemia): The child born with thalassemia major has two genes for
beta thalassemia and no normal beta-chain gene. The child is homozygous for beta thalassemia.
This causes a striking deficiency in beta chain production and in the production of Hb A.
Thalassemia major is, therefore, a serious disease.
At birth the baby with thalassemia major seems entirely normal. This is because the predominant
hemoglobin at birth is still fetal hemoglobin (Hb F). Hb F has two alpha chains (like Hb A) and two
gamma chains (unlike Hb A). It has no beta chains so the baby is protected at birth from the effects
of thalassemia major.
Anemia begins to develop within the first month after birth. It becomes progressively more and
more severe. The infant fails to thrive and often has problems feeding (due to easy fatigue from
lack of oxygen, with the profound anemia), bouts of fever (due to infections to which the severe
anemia predisposes the child) and diarrhea and other intestinal problems. Without treatment, the
spleen, liver and heart soon become greatly enlarged. Bones become thin and brittle. Heart failure
and infection are the leading causes of death among children with untreated thalassemia major.
The use of frequent blood transfusions and antibiotics has improved the outlook for children with
thalassemia major. Frequent transfusions keep their hemoglobin levels near normal and prevent
many of the complications of the disease. But repeated blood transfusions lead to iron overload
that can damage the heart, liver and other organs. Iron chelators can help rid the body of excess
iron, preventing or delaying problems related to iron overload.
76
Thalassemia and Pregnancy:
Although fertility is reduced in a woman with transfusion dependent beta thalassemia,
pregnancy may be possible in some women. A few cases have been reported in literature. It is
necessary for the obstetrician to involve in the management, a medical team consisting of
hematologist, perinatologist and a genetic counselor. Because of the physiological changes in
pregnancy, the heart, liver, spleen and the endocrine system are particularly vulnerable. Anemia
becomes more pronounced and the requirement for transfusion increases.
During pregnancy, the enhanced maternal nutritional needs must be taken care of and
multivitamins are to be administered. But, iron should be avoided because of the concern of iron
overload. Preconceptional administration of folate, which must be continued at least until the
10th week of pregnancy is important to facilitate cell division. Vitamin C in the dose of 100-150 mg
helps in removal of iron. Further, thalassemic women are more at risk to develop insulin
dependent diabetes during pregnancy. Maternal and fetal morbidity may also result from
medications used and infections.
Genetic counseling is essential for assessment of fetal risk and to explain to the mother the role of
genetic testing in pregnancy.
In a population based study conducted in Israel, Sheiner et al observed that oligoamnios and fetal
growth restriction were significantly associated with â-thalassemia minor. No significant
differences were noted regarding perinatal outcomes such as birth weight, low Apgar scores,
congenital malformations, or perinatal mortality. Patients with â-thalassemia minor were more
likely to have cesarean deliveries than were the nonthalassemic parturients (16.9% and 12.2%,
respectively). However, while controlling for possible confounders such as IUGR,
oligohydramnios, and previous cesarean delivery, with another multivariate analysis with
cesarean delivery as the outcome variable, â-thalassemia minor was not found as an independent
risk factor for cesarean delivery. They concluded that the course of pregnancy of patients with
thalassemia minor, including perinatal outcomes, is favorable. Because higher rates of IUGR
were found, they recommended closer fetal surveillance for early detection of IUGR.
Screening and genetic testing for haemoglobinopathies:
Advances in genetic research that allow precise identification of mutations of the Hb genes make
the process of identifying couples at risk for having offspring with the hemoglobinopathies
increasingly important. Although universal screening is not recommended, all pregnant women
at the initiation of prenatal care are to be subjected to CBC counts with RBC indices. Taking
relevant history is important and particular attention must be paid to Kutchi Lohanas,
Gujaratis,Sindhis, Punjabis, Kojas and Marwaris and patients of Southeast Asian, Mediterranean,
or African descent. These patients can be referred for Hb electrophoresis. Those patients who
have anemia and reduced MCV (<80 m3) and normal iron study findings also must be referred for
hemoglobin electrophoresis. High pressure liquid chromatography, if available is of additional
77
diagnostic value. The investigative profile of the thalassemic individual is more fully described in
the chapter on investigation of anemia in this monogram.
Test is offered to the partner of any carrier of hemoglobinopathies and any patient with elevated
HbA2 (>3.5%) to assess the risk to the fetus. If both partners are identified as carriers, DNA-based
tests are offered for the fetus.
Tests for prenatal diagnosis of thalassemia now include polymerase chain reaction (PCR) of fetal
DNA extracted from amniotic cells, of trophoblasts from chorionic villus sampling (CVS), and of
erythroblasts obtained from cordocentesis. Typically, CVS is performed at 10 weeks of gestation
to avoid limb reduction defects and cordocentesis is done after 19 weeks if confirmation is needed.
In many hemoglobinopathies, including sickle cell disease and most beta-thalassemias, point
mutations exist for which specifically designed oligonucleotide probes can be used, especially in
combination with knowledge of the patient's ethnicity. For some thalassemias, performing
indirect DNA testing by linkage analysis is still necessary.
Efforts to reduce the risks to the fetus incurred with invasive tests such as amniocentesis,
chorionic villus sampling, and cordocentesis have been made by acquisition of fetal cells from the
maternal circulation using magnetic cell sorting; however, this procedure is not standard. This
technique can only work in hemoglobinopathies in which the mutation has been identified
because only a small amount of fetal cells can be purified.
A fascinating advancement in prenatal diagnosis has been the development of a preimplantation
genetic diagnosis (PGD). In 1999, a team of reproductive endocrinologists reported single-cell
PCR and DNA analysis of embryos from a couple, both carriers for sickle cell disease, with
transfer of the genetically healthy embryos and subsequent delivery of healthy twins.
Preventive strategies:
The preventive programs are based on molecular diagnosis in high risk population. Screening is
carried out by testing blood indices and Hb chromatography antenatally and postnatally. PCR
and direct sequencing of DNA are done whenever required.
Premarital counseling plays a vital role. The incidence of thalassemia could be brought down if
carriers are discouraged from marrying another carrier. If both partners are diagnosed to be
carriers after marriage, they may be offered the option of donor insemination (AID) or adoption.
However, it may not always be practical to avoid biological offspring. In such couple at risk,
prenatal diagnosis and medical termination of pregnancy may be offered to prevent an affected
offspring.
Current Research on Thalassemia:
Scientists are working on better ways to remove excess iron from the body in order to prevent or
delay iron overload. They are developing and testing the effectiveness of oral iron-chelating
drugs, which could greatly simplify treatment of this disease.
78
Development of an effective form of gene therapy may some day offer a cure for thalassemia.
Gene therapy may involve inserting a normal beta globin gene into the patient's stem cells, the
immature bone marrow cells that are the precursors of all other cells in the blood.
Another form of gene therapy may involve using drugs or other methods to reactivate the
patient's genes for fetal hemoglobin. After birth, natural genetic switches "turn off" production of
fetal hemoglobin and "turn on" production of adult hemoglobin. Scientists are seeking ways to
activate these genetic switches so that they can make the blood cells of patients with thalassemia
produce more fetal hemoglobin to compensate for their deficiency of adult hemoglobin. Initial
studies of rare individuals with genetic traits that allow them to produce only fetal hemoglobin
show that they are generally healthy, demonstrating that fetal hemoglobin can be a fine substitute
for adult hemoglobin.
Thalassemia has been cured using bone marrow transplants. However, this treatment is possible
only for a small minority of patients who have a suitable bone marrow donor. The transplant
procedure itself is still risky and can result in death. Improved bone marrow transplantation
methods may lead to wider use of the technique as a treatment for thalassemia.
Resources and References:
1. Thalassemia.com
2. irondisurders.org
3. ghr.nlm.nih.gov
4. Kilpatrick SS and Laros RK.1995.Thalassemia in Pregnancy.Clin. Obstet.Gynecol,
38(3):485-496.
5. Savona-Ventura C and Bonello F.Obstet.Gynecol.Surv.994 Feb; 49(2):129-37.
6. Sheiner E et al.Beta Thalassemia minor during Pregnancy.Obstet.Gynecol.2004;
103:1273-1277.
79
Uncommon causes of AnemiaDr. Latha Venkataram, FRCOG
Consultant Maiya Hospital Bangalore
The obstetrician should be aware of the unusual anaemias which could complicate the
pregnancies leading to high maternal and perinantal morbidity and mortality. Chronic Anaemia
and Anaemias resistant to treatment in a women should be investigated further in coordination
with a Hematologist. Pre pregnancy counseling is an important aspect of care. Management
plans during pregnancy should be drawn with the involvement of hematologist. Though there is
an extensive list of unusual forms of anemia, few of them relevant to pregnancy have been
mentioned here.
Special problems in Pregnancy Comment Treatment
An enlarged spleen traps and destroys too many red blood cells
Splenectomy not advisable in pregnancy
Symptoms tend to be mild; often an enlarged spleen reduces the number of platelets and white blood cells
Treatment is aimed at the disorder that has caused the spleen to enlarge. Sometimes the spleen must be removed surgically
Worsening of anaemia in pregnancyErythropoietin not contraindicatedDialysis not contraindicatedAnticoagulant prophylaxis since more prone for thromobosis
Genetic mutation in haemopoietic stem cells affecting the red cells, granulocytes, platelets. The immune system destroys red blood cells in a sudden (paroxysmal) way, not just at night
Ferttility rate low. Abortions increased. MMR increased. Prone for thrombosis, infection, marrow aplasia in pregnancy.O.C.P contraindicated. Iucd contraindicated if granulocytes & platelets low
Can cause severe stomach cramps and clotting in the large veins of the abdomen like hepatic or mesenteric and lower limb veins
Corticosteroids relieve symptoms, but no cure is available. People with blood thrombosis need therapeutic doses of anticoagulant. Bone marrow transplantation may be needed long term
Hyperhaemolytic & aplastic crisiscan occur. Folic acid supplementation recommended
An inherited disorder that can also cause bone abnormalities, such as a tower-shaped skull and extra fingers and toes
Treatment is usually not needed, but severe anemia may require removal of the spleen
Idiopathic, medications, infections, toxins. Pregnancy rarely induces aplastic anaemia. Spontaneous resolution might occur after delivery
Termination of pregnancy recommended. Aplasia can rapidly deteriorate
The G6PD enzyme is missing from red blood cell membranes. Without the enzyme, red blood cells are more likely to break apart
Heterozygous women may havesevere anaemia. Folic acid supplementation recommended. May need transfusions
An x linked inherited disorder that almost always affects only males. About 10% black males and a smaller percentage of white people of Mediterranean origin have the disorder
Anemia can be prevented by avoiding the situations or substances (fever, diabetic crisis, aspirin, vitamin K, fava beans) that trigger it
Primary or secondary-drugs, infections, SLE, neoplasia. Pregnancy itself might cause haemolytic anaemia
Steroids to be continuedTransfusion may be requiredNeonatal anaemia may occurRecurs in subsequent pregnancy if the condition appears in pregnancy
Cause Mechanism
Enlarged spleen(idiopathic)
Anaemia secondary to renal disease
CRF
Paroxysmal nocturnal hemoglobinuria
Hereditary spherocytosis
Autosomal dominant red blood cells become misshapen and rigid, getting trapped and destroyed in the spleen
Aplastic anaemia
G6PD deficiency
Autoimmune haemolytic anaemia
80
INVESTIGATIONS IN ANAEMIA WHAT?
WHEN? AND WHY?
Dr.Jayanthy.T MD
Asst. Professor, Dept. of OBGKempegowda Institute of Medical Sciences, Bangalore.
There are spectrum of investigations done in case of anaemia. Plan of investigations for anaemia
is done 1. To confirm anaemia and assess severity of anaemia2. To investigate for type of anaemia and cause for anaemia
1. Screening & Diagnostic tests:
a. Haemoglobin estimation.(Hb) Normal values
Men 14 – 18 gm/dl
Women 12 – 16 gm/dl
Pregnancy 10.5 – 11 gm/dl
b. Peripheral blood film examination
c. Red cell indices Normal values
Packed Cell Volume (PCV) Women 35 – 45%
Men 40 – 52%
Mean Corpuscular Volume (MCV) 75 – 90 fl
Mean Corpuscular Haemoglobin (MCH) 27 – 31pg
Mean Corpuscular Haemoglobin conc (MCHC) 30 – 35 g/dl
d. Leucocytes and platelet count
e. Reticulocyte count 1 - 2%
2. Confirmatory Tests:
a. Bone marrow examination.
b. Biochemical tests.
c. Special tests to diagnose specific conditions.
Relevant Investigations specific to type of anaemia.
IRON DEFICIENCY ANAEMIA
1. Hemogolobin Estimation:
Reduced haemoglobin. It is a late manifestation. It is preceded by depletion of iron stores, then
reduction in Serum Iron. Though Hb decrease is a late sign, it is a simplest and practical test
81
2. Peripheral Blood Smear:
Microcytic, Hypochromic RBC's. Anisocytosis, Poikilocytosis, Target
cells are seen. Reticulocytes may be normal or decreased. The
differential diagnoses are Thalassemia and Pyridoxine deficiency
anaemia.
3. Red Cell indices:
PCV is decreased.
MCV, MCH and MCHC are reduced.
3. Bone Marrow Examination:
It may not be required to make a diagnosis of iron deficiency anaemia. However, when done it
shows erythroid hyperplasia and micronormoblastic reaction. There is reduction or absent
stainable iron depending on iron depletion.
5. Biochemical Tests:
a. Serum ferritin – is a first indicator of iron deficiency anaemia normal value is 15 – 300
ìg/dl. Here it may be < 12ìg/dl.
b. Serum iron is reduced to < 30ìg/dl. Normal value 50 - 150ìg/dl.
c. Total iron binding capacity (TIBC) is increased to 500ìg/dl and TIBC saturation may be
< 15%. Normal value is 250 – 450 ìg/dl.
d. Red cell protoporphyrin level – it is a sensitive indicator of iron deficient erythropoiesis.
It may be increased to 100 ìg/dl. Normal is 20 - 40ìg/dl.
e. Serum Transferrin Receptor (Tf R) – is reliable for assessing celluar iron states. In iron
deficiency there is a three fold increase in Tf R. Normal level is 4 – 9 ìg/dl. This,
combined with serum ferritin gives a complete picture of iron status.
f. Other tests to rule out chronic blood loss should be done after detailed history and
examination for example urine microscopy for haematuria, stools for ova, etc.
SIDEROBLASTIC ANAEMIA.
It can be hereditary or acquired, and findings differ in both.
a) Hereditary
1. Hb is reduced
2. Hypochromic microcytic cells are seen, some times a dimorphic picture.
3. MCV and MCH are reduced.
4. Serum iron is increased.
5. TIBC shows complete saturation.
6. Bone marrow shows ring sideroblasts, mature erythroblasts and increased stainable
iron.
b. Acquired
1. Hb is reduced.
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2. PBS – dimorphic picture, target cells, stippled cells and siderocytes, Pelger Huet
neuetrophils.
3. MCV is increased but MCH is decreased.
4. Serum Iron and ferritin is increased.
5. TIBC is decreased.
6. Bone marrow shows hyperplastic and ring
sideroblasts, Pappenheimer granules.
MEGALOBLASTIC ANAEMIA
Folic acid deficiency
a. Hb decreased.
b. PBS – Macrocytes, anisopoikilocytes, Cabot'srings, tear
drop cells, hypersegmented neutrophils (at least three
cells having more then five nuclear segments), basophilic
stippling, Howell Jelly bodies. In late stages there may be
neutropenia and thrombocytopenia.
When there is associated iron deficiency there may be many microcytic cells along with
macrocytes
c. MCV is more then 100fl. MCH is increased to more then 35pg but MCH is normal.
d. FIGLU Test (Formiminoglutamic Acid) – In folate deficiency FIGLU is increased in
urine and it is non specific and not very useful.
e. Bone marrow shows dyserythropoiesis, megaloblasts in erythroid series,
myeloid /erythroid ratio falls to 1:1.
Special tests:
a. Serum folate levels – It will indicate levels of folate for preceding few days only. It is
transient and will alter with folic acid administration. Normal is more than 5ng/ml.
b. Red cell folate levels – Normal is 160 to 640ìg/l. Reduction in this is a better indicator of folate
deficiency.
2. Vitamin B (Cobalamin) deficiency12
This may be a rare entity but when ever there are clinical features and folic acid levels are normal
in megaloblastic anaemia, cobalamin deficiency should be suspected.
Red cell indices, peripheral blood picture and bone marrow are similar to folate deficiency
anaemia, but here folate levels are normal.
Special tests:
1. Serum vitamin B assay :12
a.Microbiological assay using Euglena gracilis or Lactobacillus Leichmani.
b.Radioisotope assay
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Normal is 200 to 900 pg/dl less then 100pg/dl indicates deficiency..
2. Increased levels of both Serum Methyl malonic acid and homocystine.
3. Increased urinary excretion of Methyl malonic acid.
4. Radioactive vitaminB absorption test 12
a. Radioactivity in faeces.
b. Radioactivity in urine (Schilling test)
c. Radioactivity in liver
d. Radioactivity in whole body
e. Radioactivity in plasma
Schilling test is commonly done. This helps in knowing intrinsic factor deficiency.
Megablastic anaemia is seen in various other conditions like chronic liver disease, rheumatoid
arthritis etc. Depending on the clinical manifestations, specific investigations have to be done.
3. Dimorphic anaemia
In India and other developing countries patients manifest multiple deficiencies like iron, folic
acid, cobalamin, pyridoxine and other vitamins. In such cases there is a dual population of
macrocytic and microcytic hypochromic RBC's. In some cases macrocytic hyprochromic cells are
seen.
4. Haemolytic anaemia
In Haemolytic anaemias haemolysis is a common feature. In most of the conditions, tests for
haemolysis and findings are similar. Therefore tests common to all types of haemolytic anaemias
is discussed first followed by specific investigations in each type of disorders.
Evidences of haemolysis.
Increased breakdown of haemoglobin causes
a. Reduced haemoglobin - sometimes Hb may be normal.
b. Hyperbilirubinemia. (unconjugated)
c. Reduced plasma haptoglobin and haemopexin.
d. Increased plasma LDH.
e. Increased urinary urobilinogen.
f. Increased reticulocyte count.
Evidences of Intravascular haemolysis:
a. Haemoglobinuria and haemoglobinemia.
b. Haemosiderinuria.
c. Methaemoalbuminemia.
The specific tests for each type of haemolytic anaemias is discussed further.
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I. Thalassemia
This is quite common in our country and is a differential diagnosis for microcytic hyprochromic
anaemia.
a. Reduced Hb.
b. PBS – Microcytic, hypochromic red cells. Moderate to
severe anisocytosis and poikilocytosis ,nucleated RBC's,
plenty of target cells, tear drop cells ,granular
cytoplasmic inclusionbodies , polychromasia
reticulocytosis ismarked and more than 10%
c. MCV and MCH is markedly reduced . MCHC is normal.
d. Serum iron level is markedly increased.
e. Serum ferritin is 300 to 3000 ng/dl.
f. TIBC saturation is more than 70%.
g. Bone marrow shows micronormoblastic reaction, erythroid hyperplasia, striking
basophilic stippling and increased iron deposition and ring sideroblasts.
Other Tests
1. Decreased osmotic fragility
2. Alkali denaturation tests – This test is based on the factor that normal adult haemoglobin gets
denatured when alkali is added but fetal haemoglobin is resistant and not destroyed. This
test reveals increased HbF levels in thalassemia major.
3. Hb electrophoresis. In thalassemia minor, HbH is present in adults and Hb Barts in infants.
Electrophoresis using starch agarose gel at PH 8.6 is useful in diagnosis, which shows
increased HbF and HbA2.
4. Genomic study of DNA by Southern blotting of endonuclease is a very useful test. Prenatal
diagnosis of Thalassemia is very useful.
II. SICKLE CELL ANAEMIA:
1. Hb reduced.
2. PBS – normochromic, normocytic cells, fragmented RBC's, anisopoikilocytosis, target cells
and sickle cells are seen. Reticulocytosis is present.
3. MCV and MCH are normal. MCHC is increased.
4. Bone marrow shows erythroid hyperplasia.
Other Tests:
1. ESR is decreased.
2. Osmotic fragility is decreased.
3. Sickling test is positive. It can be demonstrated by adding Sodium metabisulphite or ascorbic
acid. Sickledex, a proprietary product is available. It detects HbS by precipitation of
deoxygenated HbS. It is rapid and reliable.
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4. Life span study of RBC's shows decreased survival.
5. Hb electrophoresis shows increased HbS.
II. HEREDITARY SPHEROCYTOSIS
1. Hb is reduced.
2. PBS – Spherocytes lacking central pallor, reticulocytosis and thrombocytopenia is seen.
3. MCV is normal, sometimes it may be decreased. MCH is normal. MCHC is raised.
4. Increased osmotic fragility.
5. cDNA – Genomic DNA analysis for molecular diagnosis may be helpful.
III. HERDITARY ELLIPTOCYTOSIS
1. Haemoglobin is reduced.
2. PBS – Ovalocytes or Elliptocytes are seen and constitute more than 50% of the cells.
3. MCV and MCH are normal.
4. Osmotic fragility is increased.
IV. CONGENITAL HAEMOLYTIC ANAEMIA
1. Hb is reduced.
2. PBS – Polychromasia, basophilic stippling, Heinz bodies, macrocytes are seen.
3. MCV and MCH is increased.
4. Enzyme assays should be done to detect various enzyme deficiencies.
a. G6PD deficiency – 1. Brilliant cresyl blue test.
2. Heinz body test.
3. Fluorescent spot test.
4. Enzyme assay.
b. Phosphokinase deficiency.
c. Pyruvate kinase deficiency.
V. ACQUIRED HAEMOLYTIC ANAEMIA
1. Hb may be normal in acute phase.
2. PBS – Polychromasia, basophilic stippling and reticulocytes.
3. Osmotic fragility test is increased.
4. Direct Coomb's test may be positive.
5. Serological test for antibodies in serum.
6. Urine test may show increased levels of coproporphyrin.
7. Other tests to know the cause may be done depending on the clinical features for eg. Malarial
parasites in malaria.
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VI. PAROXYSMAL NOCTURNAL HAEMOGLOBINURIA
1. Hb is decreased to less than 5gm/dl.
2. PBS – dimorphic anaemia.
3. Total leucocytes and platelets are reduced.
4. Reticulocytosis is seen.
5. Bone marrow shows erythroid hyperplasia.
6. Urine – Hb casts, haemosiderinuria is a constant feature
VII. APLASTIC ANAEMIA:
1. Hb is decreased.
2. PCV is decreased
3. Total leucocytes count is decreased. Differential count shows marked neutropenia.
4. Platelets are decreased.
5. PBS – usually normal cells are seen sometimes macrocytosis, anisocytosis and poikilocytosis
is seen.
6. Bone marrow is hypoplastic or aplastic, shows numerous spicules with empty fatty spaces.
Dyserythropoietic lymphocytes, plasma cells and macro phages. Relatively few
haemopoietic cells.
7. Serum Iron is increased.
8. Plasma erythropoietin is increased.
9. Coagulation profiles are abnormal.
Lastly, anaemia may be a feature in leukemias. Here leucocytes and reticulocytes are increased.
Normochromic RBC's are seen.
Bibliography:
1. Cecils text book of Medicine.
2. de Gruchy's clinical haematology in medical practice.
3. Harrison's text book of Principles of internal medicine.
4. Text book of Haemotology – basic principles and practice by Hoffman co.et al.
5. Blood – Principles to practice of Haematology by R.I. Hand , S.Lux and T.P. Russel.
6. Text book of Medical laboratory technology by Ramnik Sood.
7. Practical pathology Dr.U.Chaturvedi and T Singh.
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MANAGEMENT OF IRON DEFICIENCY
ANEMIA IN PREGNANCY
Dr. Jyothika A. Desai
Dr. P.R. Desai Hospital, Bangalore
Anaemia is not a disease. It is a sign of an underlying disorder.Treatment, therefore, must be
preceded by an accurate diagnosis of the cause and the type of anemia.
General Measures
Diet
A basic knowledge of iron metabolism in the body will help us in understanding the mechanisms
by which the iron supplements help in correcting the deficiency.
Iron absorption
Healthy people absorb around 5 to 10 percent of the iron in their daily diets. Absorption is highest
in childhood, and reduces with age. Iron is present in animal foods in organic 'heme' form and in
plant foods in inorganic 'nonheme' form. The heme and nonheme forms of iron are absorbed by
different mechanisms. About 20 to 30 percent of heme iron is absorbed compared to only 2 to 5
percent of nonheme iron. Heme iron is broken down by pancreatic enzymes and is absorbed. Its
absorption is unaffected by food factors. Non Heme iron must be in ferrous form to be absorbed
and the hydrochloric acid of the stomach converts ferric iron to ferrous iron. Iron absorption is a
slow process, taking between two and four hours. Iron levels in the body are regulated by
absorption, rather than by excretion and low body iron levels lead to improved absorption. In
cases of iron deficiency absorption efficiency increases to around 10 to 20 percent. Various food
factors affect iron absorption and the overall amount of iron absorbed from a meal will depend on
the interactions between these factors.
Enhancers
Low body stores Full body stores
Hydrochloric acid in the stomach Reduction in stomach acid
Vitamin C Tannins (e.g. in tea)
Sugars Oxalic acid (e.g. in spinach)
Haem iron Phytic acid (in dietary fibre)
Calcium and phosphorus in milk
Enhancers and Inhibitors of Non heme iron absorption
Inhibitors
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Food Fortification is a preventive measure that aims at improving and sustaining iron nutrition
on a permanent basis.Cereals, sauce, sugar, curry powder and salt are some of the items which
are fortified with iron.
Treatment of Hookworm infestation
a) Albendazole 400mgs | only in the
b) Mebendazole100 mgs twice daily for 3 days |
c) Avoiding walking barefoot to prevent Hookworm infestation
Aims of Therapy
a) To raise the Hb level
b) To replenish the iron stores
Choice of Therapy
depends upon
a) Severity of Anaemia
b) Duration of pregnancy and
c) Associated complicating factors
Principles of iron therapy
First introduced by Dr.Pierre Blaud in the 19th century.
1. Inorganic iron salts should be given orally
2. A raise in Hb concentration of about or > 0.5 gm per 100cc daily is considered a positive
response
3. Once the Hb concentration has risen to the normal range, iron therapy should be given for
a further period of 3 months to replenish the iron stores.
4. Response to parenteral iron is almost similar to oral iron- in the absence of malabsorbtion.
5. Bone marrow response and erythroid hyperplasia are seen within 48 hrs of starting
therapy and iron stores are replenished within 3 months.
Iron Therapy
can be
a) oral or
b) parenteral
Oral iron
Iron is best absorbed in the ferrous form. It is available as various salts -gluconate,
fumarate,sulphate, succinate, etc. Ferrous Sulphate is available as a 200mg tablet with 60 mgs of
elemental iron along with traces of zinc and magnesium. The therapy is started with 1 tablet
2nd or 3rd trimesters
only in the 2nd or 3rd trimesters
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thrice daily with food, followed by gradually increasing the dosage to 2 tablets thrice a day. Once
the Hb has reached normal values, it can be maintained at 1 tablet a day for 3 months to replenish
the iron stores.
Recommended daily requirement of iron:
For prophylaxis, the Govt of India recommends 100 mgs of elemental iron with 0.5 mg of Folic
Acid, but for treatment, more than 180 mgs of elemental iron with 5 mgs of Folic Acid is
recommended.W.H.O recommends 30-60 mgs of iron be given daily to pregnant women with
normal iron stores and 120-240 mgs to those with none.
Drawbacks of oral iron therapy
a) Gastro-intestinal side effects …seen in 10% of women. It is dose related and is less when the
iron is <100 mgs per day. It depends upon the amount of ionic iron - the absorbable form of
iron that comes in contact with the gastro-intestinal mucosa. The common symptoms are
epigastric distress, nausea, vomiting, constipation, diarrhoea etc.They can be avoided by
1) Starting with a small dose and gradually increasing it,
2) By changing the preparation. Carbonyl iron and Hb preparations are better tolerated
3) Giving it with meals. Slow release preparations, which are generally more expensive are said
to be relatively free from side effects. This is perhaps so because much of the iron is not
released at all or is unabsorbed and excreted unchanged.
b) Unpredictable absorption…therefore cannot be depended upon when a quick response is
desired. Iron absorption is diminished by antacids, oxalates, phosphates in bread, milk and
cereals, and tannins in tea. Iron absorption is increased by…ascorbic acid, lactate, amino-
acids, sugar, citric acid, HCL in the stomach, meat etc.
Response to therapy is evidenced by
a) Rise in Hb level…A rise in 0.1gm% or more daily is considered a positive response. Hb
response is greater in the first few weeks of therapy and is proportional to the severity of
anaemia.A rise in Hb concentration of 1gm% per wk in the non-pregnant state or 0.8gm%per
wk in pregnancy can be expected with adequate iron treatment whether oral or parenteral.
b) Haematocrit comes to normal
c) Reticulocytosis within 7-10 days
d) Subjective symptoms increased sense of well-being, improved appetite,etc
If no significant improvement is evident clinically and haematologically within 3 wks of
therapy, the diagnosis should be reviewed.
Causes of failure of improvement
a) Noncompliant patient who does not take the prescribed dosage
b) Defective absorption either because of the preparation or because of coexisting gastro-
intestinal disorders
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c) Incorrect diagnosis of the type of anaemia
d) Concurrent blood loss due to hookworm infestation or bleeding piles
e) Coexistent undiagnosed folate deficiency
f) Inhibition of erythropoiesis due to infection
Contraindications to Oral iron therapy
a) Intolerance to oral iron
b) Severe anaemia in advanced pregnancy
Indications for Parenteral iron therapy
a) Intolerance to oral therapy
b) Non compliant patient
c) Severe anaemia in advanced pregnancy
d) Malabsorbtion syndrome
Advantages of Parenteral therapy
a) Certainty of iron administration
b) Replenishment of iron stores
Routes of administration
a) Intramuscular
b) Intravenous
Calculation of total iron deficit:
Total iron deficit in adult patients may be estimated using one of the following equations (Hbt =
target Hb level; Hbo = observed or actual Hb level; Bwt = body weight)
Total Dose (mg) = 50 {0.0442 Bwt (Hbt - Hbo) + (0.26 Bwt) }
Total Dose (mg) = 2.4 Bwt (15 - Hbo) + 500
Contraindications and Precautions:
v Parenteral iron supplementation is ineffective in aplastic or hypoplastic anemia and acute
leukemia.
v Parenteral iron supplementation is contraindicated in early pregnancy, in patients with liver
disease or acute renal failure.
v IV iron products must be used with caution to minimize acute adverse reactions. An
anaphylaxis management kit should be at hand.
v Conservative estimates of iron deficit should be used to avoid iron overload.
v Measures of iron status (ferritin, total iron binding capacity, & transferrin saturation) and red
blood cell indices must be checked periodically to reevaluate the patient's need for additional
iron supplementation. Parenteral iron should not be administered to patients with ferritin >
91
800 ng/mL or transferrin saturation > 50%.
Intramuscular iron
Preparations available are Iron-Dextran (Imferon), (Ferri) Iron Sorbitol Citric Acid Complex
(Jectofer)
All preparations contain 50 mgs of elemental iron in 1 cc. Oral iron should be suspended 24 hrs
before starting parenteral iron.
The dose of Intramuscular iron calculated as per the formula which is the same as for Intravenous
iron. The total dose of Iron Sorbitol CAC is adjusted because 30% is excreted in the urine. Test
dose of 1cc is given followed by daily or alternate day IM injections in doses of 2cc.
Drawbacks
Local - pain, pigmentation, abscess formation. Few precautions taken while injecting can prevent
these local reactions like utilizing the Z technique, injecting air or saline before withdrawing the
needle and not massaging the injection site.
Systemic
a) Diarrhoea, nausea, vomiting, fever, lymphadenopathy
b) Anaphylactic reaction in 2 % of patients
c) Arthralgia, especially in rheumatoid arthritis.
d) Haemolysis
Intravenous iron The various preparations available are Iron Dextran (Imferon, Ferri), Iron
Hydroxide Sucrose Complex (Encifer) etc.Intravenous iron can be given as a single or multiple
dose without dilution or diluted as a total dose infusion. A test dose of 0.5 cc diluted with 4-5 cc of
the patient's blood is injected slowly and patient observed for 1 hour. If there is no reaction, upto 5
cc can be given slowly as a single bolus at the rate of 1cc/minute.
Total dose infusion
The total dose calculated is diluted in 1 litre of saline or dextrose. Saline is preferred as phlebitis is
less often seen. Not more than 2500mgs can be given in 1 litre.If the total dose is more than
2500mgs or 50 cc (1cc=50mg), then the total dose should be infused on 2 consecutive days.
The formulae for calculating the total dose are as follows…
a) 2.3 x wt in kgs x (15—pt's Hb% in gms) +1000mgs(for stores)
b) 0.3 x wt in lbs x (100—Hb %) + 50% for stores
c) A simple method is to give 250 mgs of elemental iron for each gm of Hb below the normal (14
gms) and add 50 % more for replenishment of iron stores.
Technique for Total dose infusion
Precautions as for a blood transfusion should be taken. The drip rate should be about 10
drops/minute for the first 20 minutes. It can be later increased to 40 drops/minute. Any reaction
92
like rigors, chest pain etc, calls for immediate suspension of the drip.
Iron Hydroxide Sucrose Complex is not licensed for total dose infusion and can be given as 5cc
(vial contains 5cc with 20mg/cc) slow IV or as a short infusion for 15 minutes with N.S for 1-3
doses per week. It has excellent tolerance with few complications.
Advantages of Total dose infusion
a) It eliminates repeated and painful IM injections
b) The treatment is completed in 1 day
c) Expenditure is less than for the IM course
Blood transfusion in pregnancy
Considered only in severe anemia close to delivery where packed cells transfusion is given. The
other major indication for blood transfusion in pregnancy is in management of acute blood loss as
in APH /PPH
Antenatal management of a case with anaemia
The prognosis is good if anaemia is detected and treated in time. Therapeutic dose of oral iron
should be started after the 14th week. The patient should be seen more often to detect and manage
the complications of anaemia such as Heart failure, Preterm labour etc. Fetal growth to be
monitored carefully as IUGR is commonly seen. Betamimetics should be given with caution in
patients with anaemia and preterm labour to avoid the risk of pulmonary oedema.
Management during labour
The aim is to have a normal delivery. Ideally, anaemia should have been treated during
pregnancy but in the event of a patient arriving in labour with untreated anaemia then in the
First stage
a) The patient should have back rest or should be in any other comfortable position
b) Pain relief should be offered
c) O2 inhalation if patient is breathless. This will also reduce the risk of fetal hypoxia.
d) Prophylactic antibiotics may be required.
e) Digitalisation if in failure with severe anaemia
Second stage
Should be shortened by Outlet forceps /vacuum. Prophylactic oxytocics should be given to
curtail blood loss.
Third stage
Should be managed actively. Significant blood loss should be replaced with fresh packed cells.
Puerperium
The problems faced are:
93
v Subinvolution of the uterus due to infection
v Poor lactation
v Thromboembolism
Oral iron should be given for at least 6 months.
Contraception
Spacing of pregnancies is very important for an anaemic woman. Progesterone only preparations
are preferred. In a non lactating woman COCs are a good alternative since blood loss during
menstruation is minimal. IUCD may be considered if there is no history of menorrhagia.
To reiterate, an anaemic woman must use an effective method of contraception and avoid
pregnancy for at least 2 yrs to give time for her iron stores to be replenished.
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29. Sharma JB. Iron deficiency anaemia in pregnancy-still a major cause of maternal mortaility
and morbidity in India. Obs Gynae Today 1999: IV: 693-701.
30. Rusia UN, Madan N Agarwal N, Sikka M, Sood SK. Effect of maternal iron deficiency
anaemia on fetal outcome. Ind j Pathol Microbiol 1995; 38:273-279.
31. Mahomed K. Routine iron supplementation during pregnancy. (Cochrane Review) The
Cochrane Library, Issue 2. Oxford; Update Software 1998.
32. Ridwan E, Schlultink W, Dillon D, Gross R. Effects of weekly iron supplementation on
pregnant Indonesian women are similar to those of daily supplementation. Am J Clin Nutr
1996; 63:884-890.
33. Bhatt RV. Poor iron compliance – the way out. J Obstet Gynecol Ind 1997; 47:185- 190.
34. Atukorala T, deSilvla LD, Dechering WH, Dassenaeike TS, Perera RS. Evaluation of
effectiveness of iron folate supplementation and antihelminthic therapy against anaemia in
pregnancy- study in the plantation sector of Sri Lanka. Am J Clin 1994; 60:286-292.
35. Bhatt RV. Anaemias in pregnancy: early diagnosis and treatment. J.Ind Med Assoc 1995;
93:80-82.
36. Indian Council of Medical Research. Field Supplementation Trial in Pregnant Women with
60 mg, 120 mg and 180 mg of Iron with 500 ugm., of Folic Acid . New Delhi: ICMR, 1992
37. Sood SK, Madan N, Rusia U, Sharma S. Nutritional anaemia in pregnancy and its health
implications with special reference to India. Ann Nati Acad Med Sci 1989; 25:41-50
38. Prema K. Anaemia in pregnancy. In:Ratnam SS, Rao KB, Arulkumaran S. (eds) Obstetrics
and Gynaecology,. Vol. I Madras: Orient Longman,1992; 42-53.
39. Basu SK. Administration of iron dextran complex by continuous intravenous infusion. J
Obstet Gynaecol Br Cwlth 1965; 72:253-258
40. Blot I, Papiemik E, Kaltwasser JP, Werner E, Techernia G. Influence of routine
administration of folic acid and iron during pregnancy. Gynecol Obstet Invest 1981; 12:294-
304.
41. Swalin RA, St. Clair L. The role of folic acid in deficiency status and prevention of disease. J
Fam Pract 1997; 44:138-144.
42. Chanarin L. Folate deficiency in pregnancy. In: Chanarin I (ed). The Megaloblastic
Anaemias, 3rd edn. Oxford: Blackwell, 1990:140-148
43. Iyengar L. Folic acid requirements of Indian pregnant women. Am J Obstet Gynecol 1971;
111: 13-16.
96
Eating right, right from now!
Dr. Sita Bhateja
Sita Bhateja's Nursing Home, Bangalore
Anemia is the commonest cause of poor health amongst Indian women. There are so many causes
of this malady but we shall talk only about the nutritional anemia. About 60% of the women have
hemoglobin less than 10 gms/dl. They are not always from the lower socio-economic class. This is
also prevalent amongst the middle and high socio-economic strata of women in our country. This
is basically due to poor knowledge about nutrition.
Causes of poor nutrition
1. Lack of information regarding balanced diet, specifically the anti-anemic factors.
2. Stereotype of menu – same quality of food day after day.
3. Eating wrong type of food, what is more commonly known as junk food! Foods which are
uncooked, cold aerated drinks, white flour preparations, and sweet, sugar coated food items
like chocolates are the types of food which have poor nutritional value. These food items kill
appetite and are habit-forming.
4. In case of pregnant women and adolescents the requirement is much more. This must be
taken into account by the individuals while they are preparing their food and they must be
educated about their diet by the treating doctors.
5. If there is heavy blood loss due to heavy menstrual cycle, bleeding piles or any other cause for
chronic blood loss, it will cause anemia.
In early months of pregnancy women develop anemia due to vomiting which causes loss of
nutritional products from the diet.
There should be a balanced diet. Many of these dietary factors are inter-dependent for absorption.
Variety of food is the key to getting all the ingredients which would prevent nutritional anemia.
Chronic deficiency of hemoglobin leads to poor vitality and fatigue. Essential ingredients for
preventing anemia are:
Iron
Folic acid
Vitamin B12
Vitamin C
Trace elements Zinc, Chromium, Selenium.
The chart shows what is the requirement and in which food they are to be found.
97
The modern educated woman is aware of the problems. Nowadays some of them come for
preconception checkup. That is the best time to diagnose pre-existing anemia and cure it well
before the pregnancy. This will ensure proper oxygen supply to the fetus from the very beginning.
Chronic oxygen deficiency due to maternal anemia will produce poor pregnancy outcome.
The modern diet is very deficient in folic acid because it is destroyed by cooking. Therefore some
fresh green raw vegetables will be desirable. Eg. Lettuce, sprouted beans. In addition folic acid
supplement is very necessary. Vitamin B12 is an ingredient which is found mostly in non-
vegetarian diet. Lot of people in India are vegetarians. It is necessary to supplement the diet with
B12 tablets.
Vitamin C is another unstable ingredient. It promotes iron absorption. Citrus fruits and amla are
good sources. Unpeeled potatoes are a good source of vitamin C. Other trace elements may not be
easily available in diet. Therefore the simplest solution is to supplement these with tablet or
injections.
Calories may be sufficient in the diet but due to lack of information or due to poor eating habits
anemia is still very prevalent. 60% of female population has hemoglobin of 10grms or even less.
Hemoglobin of more that 11grms is very uncommon. This makes them vulnerable to
complications. Even very small blood loss during delivery may cause symptoms of hemorrhage
in these cases. It is necessary to repeatedly check hemoglobin levels and attend to the nutrition
supplements.
This cause of maternal mortality and morbidity can be easily prevented by proper nutrition and
supplementation. It is not possible to procure all anti-anemic factors in the diet. In view of this
supplementation is the best way to fight this scourge which leads to poor vitality.
Our aim is to have every woman with hemoglobin of at least 12gms. This will help in reducing
mortality and morbidity of the mothers and open the doors to happiness in the family. She can
then have energy to look after her family and also to produce enough milk for her new born baby.
Let us make the Indian women enjoy her role to the full.
98
Ideal Body Weight and Recommended Caloric Intake During Pregnancy
Height Ideal Body Weight (Kilograms)
Recommended Caloric Intake During Pregnancy ( 35 Kcal / Kg )
17014'10” 48.6
17504'11” 50.0
17995'0” 51.4
18455'1” 52.7
18945'2” 54.1
19575'3” 55.9
20375'4” 58.2
21005'5” 60.0
21635'6” 61.8
22265'7” 63.6
23005'8” 65.7
23005'8” 65.7
23565'9” 67.3
24195'10” 69.1
Nutrient Normal RDARDA during pregnancy
Risks of deficiency in mother and fetus Sources
Zinc 12 mg/ day 15 mg/ day
Intrauterine growth retardation, malformations, premature and postmature birth, LBW, perinatal death and abnormal delivery with dystocia and placental abruption
Red meat, sea food, yogurt, bread, lentils, milk, peas, baked potatoes.
Iron 15 mg/ day 30 mg/ dayMaternal anemia, fetal anemia, LBW and preterm delivery
Apple, jaggery, dry fruits
Copper 1.5 - 3 mg/ dayPlacental insufficiency andintrauterine death
Cooking in copper vessel1.5 - 3 mg/ day
Chromium 50 - 200 :g/ dayGestational diabetes and hyperglycemia
Onions, tomatoes, broccoli, white meat, grape juice, red meat, green beans.
50 - 200 :g/ day
Selenium 55 :g/ day
Neural tube defects, sudden infant death syndrome and first- trimester miscarriages
Asparagus, mushroom,garlic, red meat, sea food.
65 :g/ day
Iodine 150 :g/ day
Miscarriage, stillbirths, congenital anomalies., goiter, cretinism, impaired brain function and hypothyroidism
Iodized salt, sea food175 :g/ day
Folic acid Neural tube defects in fetus
Meat, liver ( best source), chicken kidney, egg yolk, almonds, lentils, beetroot, banana, whole wheat grain
15 :g/ day
Nutrient Requirements In Women
99
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100
Mirror, mirror on the wall….
which is the best iron of them all?
Dr. Susheela Rani B. S.
Manjushree Speciality Hospital Bangalore
Iron deficiency is the most common nutritional disorder in the world. The World Health
Organization ranked it as the seventh most important preventable risk for disease, disability, and
death in 2002. In a developing country like ours the woman is always in a state of precarious iron
balance during the reproductive years. She is born anemic, grows anemic, and enters the
pregnancy in an iron deficient state and becomes even more anemic with successive pregnancies.
The iron stores are not well developed because of poor nutritional intake, recurrent infections,
menstrual blood loss and repeated pregnancies. Gender discrimination in our country ensures
that the girl child lacks access to balanced diet, adequate health care and proper education. Thus
the average Indian woman is almost always in an iron deficient state.
The most common strategies employed to control the iron deficient state are:
1. Food fortification
2. Iron supplementation
Supplementation of Iron in pregnancy – 60mg /day
Treatment of Iron deficiency – 120 - 180mg /day
Iron Toxicity
Iron poisoning is rare in adults, but serious acute toxicity may occur in children. The estimated
lethal dose of iron is 200 to 300 mg/kg. The majority of cases are non-fatal and without serious
morbidity. Fatalities are generally attributable to accidental ingestion of adult, rather than
paediatric, iron supplements. Many iron preparations are therefore aimed at making them safe by
increasing the lethal dose.
Iron fortification of food
Food-iron fortification (at levels to provide around 5–15 mg/day, in foods such as wheat flour,
salt, sugar, rice, fish sauces and pastes) is common in developing countries, where iron
The Recommended Dietary Allowance (RDA) for females
Category
Adolescent girls 18 mg
Mixed Diet Veg Diet
26 mg
Premenopausal 25 mg 33 mg
Postmenopausal 8 mg 14 mg
101
deficiency is widespread and food fortification is relatively inexpensive in comparison to
pharmacological supplementation.
In the UK there is mandatory iron fortification of white and brown flour.
Many breakfast cereals, malted drinks, some biscuits and snack foods are
fortified on a voluntary basis. Ferrous sulfate is the most commonly used
fortificant for cow milk or infant formulas. Rice fortified with a standard
ferrous sulfate mix has been used successfully in the Philippines. Curry
powder has been successfully fortified with iron- EDTA in South Africa.
The technology for fortifying common salt with iron has been developed
indigenously in India.
A double-blind controlled iron fortification trial using NaFeEDTA in masala powder (10 mg/g
masala) was directed towards an iron deficient Indian population. The iron status of the fortified
groups improved more than that of control subjects, the prevalence of iron deficiency anaemia
decreased from 22 to 5% in fortified females. It is reported that fortified subjects with normal iron
status did not accumulate excessive body iron and no adverse effects were observed.
Another double blind randomized controlled study was conducted among school children in
Bangalore, India. The study showed that when school children were fed with extruded rice
fortified with micronized ground ferric pyrophosphate in their midday meal for 7 months, iron
deficiency anemia was reduced by 50%.
Thus it has been proven beyond doubt that iron fortification of food can make a positive
difference to the health statistics of our country.
Pharmacological iron supplementation
A wide range of iron containing products (more than 70) is available in pharmacies. These include
products that contain only iron salts, iron combined with zinc and/or folic acid and numerous
multinutrient products. The indication for products that only contain iron is the treatment or
prevention of iron deficiency. The multinutrient products have a range of indications including
use when intake or absorption of nutrients may be suboptimal such as postoperatively, in severe
chronic disease, in malabsorption syndrome, in pregnancy and where diet is restricted.
A factory where wheat flour is
fortified with iron
102
Side effects of Iron supplementation
Therapeutic doses of iron supplements, which are prescribed for iron deficiency anemia, may
cause gastrointestinal side effects such as nausea, vomiting, constipation, diarrhea, dark colored
stools, and/or abdominal distress.
Enteric coating & delayed release
Modified release [MR] preparations, some in 'Spansule' formulation, are designed to release iron
gradually as the preparation traverses the GI tract so that at any given time, only a small amount
of iron is present in the lumen. The advantages
claimed are less GI irritation and a long duration of action permitting once or twice daily dosage.
However, these preparations are likely to carry the iron beyond the first part of the duodenum
where the conditions for iron absorption are optimal and the lower incidence of intolerance may
well be due to the fact that a smaller quantity of iron is actually released and absorbed.
Furthermore, technical failure of the preparation can lead to dose-dumping and even to entire
tablets being passed out in stool.
Iron absorption enhancers
A variety of substances designed to enhance the absorption of iron has been marketed, including
surface acting agents, carbohydrates, inorganic salts, aminoacids and vitamins. One of the more
popular of these is ascorbic acid. When present in an amount of 200mg or more, ascorbic acid
increases the absorption of medicinal iron by at least 30%. However the increased uptake is
associated with a significant increase in the incidence of side effects; therefore addition of ascorbic
acid seems to have little advantage over increasing the amount of iron administered. It is
inadvisable to use preparations that contain other compounds with therapeutic actions of their
own, such as Vit B12, folate, cobalt etc, since the patient's response to the combination cannot be
easily interpreted.
Tips to enhance iron absorption
1. Starting with half the recommended dose and gradually increasing to the full dose will help
minimize the side effects.
2. Taking the supplement with food also may help limit gastric symptoms at the cost of reduced
absorption.
3. Inclusion in the meal fresh fruits or fruit juices and other sources of vitamin C such as
tomatoes, spinach, cabbage, cauliflower, potatoes and other green leafy vegetables.
4. Consume milk, cheese and other dairy products as between-meal snacks rather than at
mealtimes
5. Separate tea drinking from mealtime by at least 2 hours
A number of iron preparations are currently available in the Indian market for the prevention and
treatment of iron deficiency anemia. Each preparation claims some benefit over the others leaving
103
the physician in considerable confusion. How does one choose the best
iron supplement? Apart from being bio available, clinically effective
and having minimal side effects, an ideal iron supplement needs to be
safe and cost effective. While the effectiveness of most iron
preparations available in the market remain the same, the benefits
claimed are in reducing the side effects, making them tolerable and
increasing their safety.
Oral Iron Supplements
1. Ferrous salts
All dietary iron has to be reduced to ferrous form to enter the mucosal cells. Hence bivalent iron
salts like ferrous sulfate, fumarate, gluconate, succinate, glutamate and lactate have been
preferred over ferric salt preparations. In addition these salts are amongst the cheapest
preparations of iron available for medicinal use.
Bioavailability
These salts have uniformly good bioavailability. However, the bioavailability decreases
markedly in the presence of dietary inhibitors like phytates, tannic acid etc. They cannot be added
to other foods/milk/fortified formulas for the same reason.
Clinical efficacy
Despite being efficacious and cheap with good bioavailability, ferrous salts have several
disadvantages particularly the high incidence of gastrointestinal side effects (~23 %). Teeth are
known to be stained with liquid preparations. Ferrous sulphate has a salty astringent taste.
Safety issues
Any over dosage of the salt can easily override the 'mucosal barrier' to cause acute iron toxicity.
The LD50 for ferrous sulphate is 320mg/Kg body weight.
Salt of Iron
Ferrous sulphate
Trade name - Pharma
Ferrous fumarate
Iberol - Upjohn
Ferrous gluconate JP Tone - Jagsonpal
Ferrous lactate
Irex 12 - MicroAutrin - WyethSofteron - AristoRediplex - PfizerLivogen Z - Merck
Ferrous succinate Hematrine Novartis Pharma
Ferrous ascorbate Ferium XT - EmcureOrofer XT - Emcure
104
2. Ferric salts
Ferric salts have traditionally not been preferred over ferrous salts as the ferric ion first requires
reduction to ferrous form in the intestinal lumen and usually this reducing capacity is not enough
to reduce doses of iron therapeutically administered.
Bioavailablility
The bio-availability of iron from ferric salts is 3 to 4 times less than that of ferrous sulphate.
Therefore, the dose of ferric salts needs to be 4 times more than ferrous salts to achieve similar
therapeutic effect.
Safety
Ferric salts carry the inherent advantage of a poor poisoning potential given the limited reducing
ability of the gastric contents. Ferric ammonium citrate (18% elemental iron) is the most
commonly used of these salts.
3. Iron Amino-acid chelates
Iron amino-acid chelates are conjugates of the ferrous or ferric iron with amino-acids. Although
numerous conjugates have been formulated the most studied of these are ferrous bis-glycinate
(20% elemental iron content), ferric trisglycinate and ferrous glycine sulphate. They have no
effect on the color or taste of food products.
Bioavailability
Their main advantage lies in their relatively high bioavailability in the presence of dietary
inhibitors. It is theorized that the chelates prevent iron from binding to inhibitors in food or
precipitating as insoluble ferric hydroxide in the pH of the small intestine. Studies have shown
that iron absorption from ferrous bisglycinate is better than ferous sulphate in the presence of
dietary phytates.
Safety
These conjugates have low pro-oxidant properties thereby limiting free radical damage and are
environmentally stable.
Trade name
Ferrous bisglycinate Ferose - CFL
Pharma
Fe Glycine sulphate Hemfer - Am. Rem
105
4. Iron (III) Polymaltose Complex (IPC)
IPC is a novel iron preparation, which contains non-ionic iron and polymaltose in a stable
complex.
Bioavailability
IPC and FS have been demonstrated to have equivalent bioavailability. Absorption of IPC is not
affected by food or milk, enabling administration without consideration of the timing of feed.
Also, to date there are no reports of any interactions with foods or medicines.
Clinical efficacy
The usefulness of IPC in the treatment of IDA has recently been a topic of much debate. Contrary
to earlier reports, there are several other reports of inadequate or slower rise in hemoglobin.
Safety
Iron of IPC is absorbed in the intestine through a self-limiting competitive interchange of ligands,
so that the intestinal transport system is saturated in case of over dosage. Accidental intoxication
with IPC is therefore rarely seen.
5. Carbonyl Iron
Carbonyl iron is a small particle preparation of highly purified (98%) metallic iron. 'Carbonyl'
describes the process of manufacture of the iron particles (from iron pentacarbonyl gas). The
particle size is less than 5 microns as compared to Ferrous fumarate which is 30-100microns. The
stomach acid solubilizes this iron. In the process of this solubilization H+ ions are consumed
thereby increasing the gastric pH. Also, as a result the absorption of iron is slow (permitting
continued release for 1 to 2 days) and self limited by the rate of acid secretion by the stomach
mucosa.
Bioavailability
After oral administration of equivalent amounts of carbonyl and ferrous iron, the amount of iron
absorbed, and the internal distribution of absorbed iron are all similar. As a food fortificant its
advantages include lack of change in color or taste of the foodstuff and environmental stability.
Clinical efficacy
Carbonyl iron is as effective as Ferrous sulphate in bringing about mean Hb increase. Estimates of
net changes in total body iron suggested that the overall bioavailability of carbonyl iron was high,
about 70% that of ferrous sulfate. Subsequent studies have shown that Carbonyl iron was as
effective and safe in prevention and treatment of iron deficiency with lesser side effects compared
to FS.
Trade name
Mumfer Z Glenmark
Pharma
106
Safety
Carbonyl iron is much less toxic than ionized forms of iron. Whereas the lethal dose of FS is 320
mg/kg. Toxicity studies of carbonyl iron in animals demonstrated a lethal dose of 50,000 to 60,000
mg/kg
6. Iron EDTA
Ethylene diamine tetraacetic acid (EDTA) is a hexadentate chelator, which can combine with
virtually every metal in the periodic table. Binding of EDTA with iron is favoured in the acid
milieu of the stomach, irrespective of whether the EDTA is administered as CaNa2EDTA,
Na2EDTA, or NaFeEDTA, but in the more alkaline medium of the duodenum the iron is
exchanged, in part, with other metals. The iron released from EDTA is absorbed by the normal
physiological mechanisms. When NaFeEDTA is present in a meal, the iron moiety exchanges
with the intrinsic food iron and the EDTA partially protects the iron in this common non-heme
iron pool from the effects of inhibitors of iron absorption, such as phytates and polyphenols.
Efficacy
When iron is added as NaFeEDTA to an inhibitory meal, it is two to three times better absorbed
than is iron added as ferrous sulfate.
Safety
There is no evidence that NaFeEDTA in the dose range proposed for food fortificants (5 to 10 mg
iron daily) will have any direct toxic effects. Na2EDTA and CaNa2EDTA have proved safe over a
number of years, while the Joint FAO/WHO Expert Committee on Food Additives concluded in
1999 that NaFeEDTA "could be considered safe when used in supervised fortification programs"
NaFeEDTA seems to be an appropriate fortificant for developing countries; its cost is about six to
eight times that of ferrous sulfate in terms of equivalent amounts of iron. Its better absorption (a
factor of 2-3) might make it possible to halve the daily fortification level but, it still remains
expensive and there is a pressing need for food grade NaFeEDTA at more affordable prices.
Trade name
Fefol Z GSK
Pharma
Carboflot Glenmark
Richar Dabur
Ferox Micronova
Café Kit Aristo
Trade name
Redfine Dr. Reddy's Lab
Pharma
Nobefer plus Ochoa
Haemgrow Fem Care
107
7. Other iron formulations
Several other iron preparations are in various stages of development or being gradually phased
out. Heme based preparations. Hemoglobin as a source of iron was promoted on the basis of the
high bioavailability of heme iron. However the iron content of hemoglobin is 0.34 %. As a result
300 mg of hemoglobin is required to deliver 1 mg of elemental iron which leads to large volumes
and prohibitory costs.
Newer preparations
Ones under study include ferrous oxalate, microencapsulated ferrous sulphate and
microencapsulated ferrous fumarate. Ferrous oxalate has been recently found to have good
efficacy and low toxicity in studies conducted on piglets.
Sprinkles
Recently, a supplement containing microencapsulated
ferrous fumarate (plus ascorbic acid) has been developed
which can be sprinkled on any complementary food at the
table given by the caregiver. Sprinkles are sachets (like small
packets of sugar) containing a blend of micronutrients in
powder form, which are easily sprinkled onto foods
prepared in the home. Any homemade food can be instantly
fortified by adding Sprinkles. Iron being encapsulated does
not change the taste, colour or texture of the food to which Sprinkles are added.
Similarly, a ferrous sulphate preparation microencapsulated with phospholipids was found to
have equivalent bioavailability to FeSO4. These may have important implications for community
intervention programmes in which initial high-dose treatment is needed because of a high
prevalence of anaemia.
Conclusion
v In a country like India, where iron deficiency is rampant, fortification of food with iron
when introduced on a large scale will make a great impact in the health of our women.
v Ferrous sulfate remains the standard first-line treatment of iron-deficiency anemia given its
general tolerability, effectiveness, and low-cost but with the possible risk of iron toxicity.
v Carbonyl iron, iron chelates, NaFeEDTA are as good as Ferrous sulphate in terms of
haemoglobin rise but are more biovailable and / or better tolerated. All these preparations
are much safer than Ferrous sulphate in terms of toxicity.
108
Bibilography
Joydev Mukherjee Iron deficiency anemia in pregnancy, Rational Drug Bulletin, Vol12, No1, Jan-
Mar 2002
Stoltzfus R., Dreyfus M.L.. Guidelines for the use of iron supplements to prevent and treat iron
deficiency anemia.
Edited by INACG, WHO and UNICEF. IUNACG. Washington.1998
Food Fortification Approaches, IH552 Elimination of Micronutrient Malnutrition
Expert group on Vitamins and Minerals EVM/00/12.REVISEDAUG2002
Rebecca J. Stoltzfus, Michele L. Dreyfuss Guidelines for the Use of Iron Supplements to Prevent
and Treat IDA, Int Nutritional Anemia Consultative Group
Peter Jacobs, Lucille wood, Better tolerance of IPC compared with Ferrous sulphate in the
treatment of Anaemia, Hematology 2000, Vol: 5, p77-83
Morgan EH, Oates PS. Mechanisms and regulation of intestinal iron absorption Blood Cells Mol
Dis. 2002 Nov-Dec;29(3):384-99
Devasthali SD, Gordeuk VR, Bioavailability of carbonyl iron: a randomized, double-blind study.
2: Eur J Haematol. 1991 May;46(5):272-8.
Gordeuk VR, Brittenham GM, High-dose carbonyl iron for iron deficiency anemia: a randomized
double-blind trial. Am J Clin Nutr. 1987 Dec;46(6):1029-34.
Anna EO Fisher, Declan P Naughton Iron supplements: the quick fix with long-term
consequences Nutriton Journal, Jan 2004, Vol 32, p 1-5
Christofides A, Asante KP, Multi-micronutrient Sprinkles including a low dose of iron provided
as microencapsulated ferrous fumarate improves haematologic indices in anaemic childre.
Matern Child Nutr. 2006 Jul;2(3):169-80
Zimmermann MB, Muthayya S, Moretti D, et al. Iron fortification reduces blood lead levels in
children in Bangalore, India. Pediatrics. 2006 Jun;117(6):2014-21.
109
REFRACTORY ANEMIAS IN PREGNANCY
Dr. Biliangady Reeta H. DNB, DGO
Director: 'NORTH STAR' Hospital for Women
Bangalore
Definition: Refractory anemia is anemia which does not respond to therapy or shows incomplete
response to adequate doses of hematinics.
CASE - DISCUSSION
Mrs. G aged 22 years seen at fifteen weeks gestation with Hb of 7.3g% PCV of 23% is started on
seen at 15 weeks gestation is started on iron supplement containing 60mg of elemental iron in a
dose of two tablets per day four weeks later a repeat Hb test shows Hb to be 7.5g% and a PVC of
24%. A peripheral smear at this time is reported as one of Microcytic Hypochromic type. The iron
preparation is changed from one of ferrous gluconate to ferrous fumarate and Hb is repeated after
four more weeks. The report is given as 8.0g%. This is a common situation encountered in clinical
practice.
Normal expected response to iron therapy: Hematological response to iron therapy in the form of
increased Hb varies with the degree of anemia. When anemia is exclusively due to iron deficiency
Hb takes usually two months to reach normal values. However when there is no cause for anemia
other than iron deficiency the Hb should increase to a point half way between the starting level 1
and the normal in about eighteen days . If this does not happen one should find out the cause for
refractoriness to therapy.
Causes of refractoriness to therapy:
i. Wrong diagnosis
ii. Non Compliance.
iii. Persistent cause for anemia.
Wrong Diagnosis: Failure of response to treatment is often due to wrong clinical diagnosis of the
cause of anemia or wrong diagnosis of the type of anemia.
The commonest type of anemia encountered in pregnancy is iron deficiency anemia..
Megaloblastic anemia however is seen in only 3 – 4% of women with anemia during pregnancy
and in the vast majority it is due to Folic acid deficiency Vitamin B deficiency begins often in the 12
third trimester or after delivery and is mainly due to dietary deficiency which commoner
amongst vegetarians. Clinical manifestations develop when the tissue stores are completely
exhausted. Addisonian Pernicious anemia is rare in the reproductive years. Also severe
Vitamin B deficiency is associated with infertility. Chronic tropical sprue is another rare cause 12
of Vitamin B deficiency in pregnancy when anemia is refractory to iron therapy Folate and 12
110
Vitamin B deficiency is to be suspected and investigations must be directed accordingly. The 12
essential feature of iron deficiency anemia is diminished concentration of hemoglobin in
microcytic red cells where as the red cell number need not be reduced. The Mean Corpuscular
Volume (MCV) and Mean Corpuscular Hemoglobin (MCH) are reduced.
The first indication of megaloblastic anemia, irrespective of whether it is Folate or Vitamin B12
deficiency in pregnancy is an elevated MCV. A reticulocyte count count however might help to
differentiate Folate from B deficeincy the count is normal in Vitamin B and elevated in Folate 12 12
deficiencies. Also in case of iron deficiency anemia which is not accompanied by folate deficiency
hypesegmentation of polymorphonuclear leucocytes is the characteristic feature. This is absent in
associated folate deficiency. Hence diagnosis of folate deficiency in pregnancy is on morphologic
grounds and is best done by examining a smear of bone marrow aspirate. (For details refer to
chapter 'Investigations; What, When & Why')
Management of Folate Deficiency in Pregnancy: WHO recommends a daily dose of 400µg of
Folate during pregnancy and postpartum. Since the diet of majority of pregnant women does not
provide this requirement it is recommended to supplement pregnant women with 0.4mg per day 2
of Folic acid Once megaloblastic erythropoiesis is established it is an indication that there is
megaloblastic change in the gastrointestinal tract also. This is associated with malabsorption and
treatment becomes difficult. However as a first line of treatment oral folic acid in a dose of 5.0mg
per day is recommended. In case of persisting anemia parenteral folic acid may have to be tried. 3
The recommended dose is 1 mg per day for one week .
The recommended intake of Vitamin B is 3µg per day during pregnancy which is available in the 12
diet of a non - vegetarian. However a strict vegetarian needs to be supplemented. In case of
established Vitamin B deficiency parenteral Cyanocobalamin should be administered in a dose 12
of 250µg per month. In women close to delivery cyanocobalamin in the dose of 100µg per day for a 3
week may be necessary .
Hemoglobinopathies: Hypochromic anemia in pregnancy is mainly due to iron deficiency.
However if the anemia does not improve in spite of adequate iron and folate supplements it is
necessary to rule out the less common situations where the red cell morphology is abnormal not
due to lack of iron but is due to lack of iron utilization or due to abnormal globin synthesis in the
red cell precursor. Hemolytic anemias which could be either acquired immune hemolytic type or
hemolytic anemias associated with hemoglobinopathies e.g. sickle cell trait, beta thalassemia
minor and sickle cell disease (For details refer to relevant chapters).
Noncompliance as a cause of refractory anemia: It is common among pregnant women in our
country to either take iron irregularly or discontinue therapy often because of gastrointestinal
side effects. A detailed questioning is necessary. Often one may have to obtain the details from the
spouse or a caretaker at home. Iron intolerance in the form of nausea, vomiting, abdominal
discomfort, colicky pain, diarrhea or constipation with conventional therapeutic dose is common
111
in pregnancy. Symptoms are often dose related. These can be avoided by starting smaller doses of
iron which can be increased gradually and also by administering iron with meals or immediately
afterwards. A sustained release preparation of iron can be tried if symptoms persist. In case this
too fails parenteral iron therapy is required (For details refer to chapter on 'Mirror Mirror on the
wall which is the best Iron of them all').
Persisting Cause for Anemia: If there is a persistent hemorrhage, occult or obvious it can lead to a
partial or complete failure of response to iron therapy. An occult cause is often in the
gastrointestinal tract which requires evaluation in the form of stool examination and GI
endoscopy. An obvious cause of hemorrhage like hemorrhoids or fissure in ano should be treated
appropriately. Hookworm infestation still remains a major cause of persisting anemia, especially
in the rural pregnant women and women of lower socioeconomic strata.
Less common causes of failure of response to iron are
a. Disorders affecting bone marrow function like
i. Chronic Infections e.g. malaria, urinary tract infection, tuberculosis.
ii. Worm infestations
iii. Chronic Renal Insufficiency.
iv. Co existing B and Folate deficiency 12
b. Malabsoption of Iron as in
i. Alimentary tract disease e.g. chronic diarrhea, irritable bowel syndrome.
ii. Occult Malabsorptive Disease.
c. Protein Calorie Malnutrition
d. Improper administration of iron e.g. administration of Calcium and Iron together impairs
iron absorption.
e. Undiagnosed hypothyroidism.
f. Bleeding hemorrhoids and fissure.
In these situations the underlying cause for lack of response should be treated and in case of
malabsorption parenteral iron therapy is to be considered.
References
1. G. Richard Lee. Iron deficeincy and Iron deficiency anemia In. Wintrobe's Clinical
Hematology. 10th Ed. Williams & Wilkins; 1998; 979 – 1010.
2. Stoltzfus R.J. et al guide lines for the use of Iron Supplements to prevent and treat Iron
deficiency anemia on behalf of the International Nutritional Anemia consultative group
(INACG) Washington, 1998, International life sciences Institute press.
3. Bitran J. D et al Megaloblastic anemia during pregnancy J Rprod Med 1977; 19; 186 – 192
112
Hemotherapy In ObG :
When, why And How?
Dr. Shivaram C,
Chief, Transfusion services,
Manipal Hospital, Bangalore.
One of the earliest documents on Blood transfusion by Andreas Libavius(1546-1616) reads as
follows:
“Let there be a young man , robust, full of spirituous blood, and also an old man thin, emaciated
and exhausted. Let the performer of the operation have 2 silver tubes fitting into each other. Let
him enter the artery of the young man, and put in one of the tubes. Let him open the artery of the
old man and put the female tube into it and then the two tubes being joined together the blood of
the young man will pour into the old one as it were from a fountain of life, and all his weakness
will be dispelled.”
The first recorded man-man transfusion transfusion was carried out by James Blundell, an
English obstetrician who saved the life of a lady who was having severe post partum hemorrhage
by transfusing the husband's blood at a time(1818) when even blood groups were yet to be
discovered by Karl Landsteiner(1900).
However, today we can no longer rely only on spirituality for safe blood, nor is husband's blood
considered appropriate for the wife to avoid sensitization with paternal antigens. However,
husband's can receive wife's blood since they don't give birth to babies!
Blood safety has three elements.
1>Safe donor (Altruistic Voluntary blood donor)
2>Safe blood ( Good testing methodology-ELISA/NAT )
3>Safe Transfusion by clinicians-the end users of blood.
Why do women need blood ?
According to a nationwide Indian study carried out by Tim Bray etal
Adult recipients account for 87% of transfusions, and amongst the age group of 25–34, 73% of
transfusions were for women. Anaemia was listed as a reason for 60% of transfusions, surgery for
42%, acute haemorrhage for 26% and pregnancy for 16%. Seventy-four per cent of adult
transfusions were inappropriate.
According to another study in Bangalore (due for publication) 3 out of 4 deaths that took place in
Bangalore as a consequence of Post Transfusion GVHD in 2005-2006 were caused by
encouragement / acceptance of relatives' blood by Obstetrician / gynaecologists.
Anemia among Indian women is a very common entity. According to a survey 52 % women have
anemia and 17 % have moderate to severe anemia. MMR in India continues to be high. While the
113
IMR has declined significantly over the years a proportionate drop in MMR is yet to be seen.
Anemia is responsible for 14-24% of the maternal deaths, while bleeding during pregnancy is
responsible for 16-26% of maternal deaths. Access to good quality blood / blood components
coupled with its rational use can significantly contribute to reducing MMR in India.
Comparison with rest of the world:
The need for transfusion of red blood cells (RBC) during pregnancy and the peripartum period is
fairly significant occurrence seen in 1% to 2% of all pregnancies in the developed countries. It has
been estimated that RBC transfusions are given in 0.3% to 1.7% of vaginal deliveries, between
0.7% and 6.8% of cesarean deliveries, and in as much as 8.6% of cases of ruptured ectopic
pregnancies.(Obstetrics & Gynecology 2004;104:1000-1004 ) Although no Indian data is
forthcoming on this, blood usage especially whole blood usage in pregnancy / peripartum
period is very common in India. Use of whole blood to reach that magical figure of 10 g% is
probably unnecessary in majority of cases.
As a general rule, only RBC transfusions should be given that too, only when absolutely
necessary. This will minimize the risks of exposure to allogeneic blood products and risk of
exposure to infections. Use of whole blood in pregnancy to correct anemia overburdens the
already burdened heart. Use of whole blood for massive blood loss corrects anemia but leads to
dilution of platelets and coagulation factors leading to complications of massive transfusion like
coagulopathy, acute DIC.
FRESH WHOLE BLOOD:
Use of fresh blood to correct platelet deficiency and clotting factor deficiency (result of massive
transfusion with whole blood) is not practically possible due to the volumes involved. Further,
use of fresh blood necessitates screening by the less accurate Rapid/spot tests as opposed to the
more accurate ELISA tests. Further, infectious agents like T.Pallidum can survive in fresh blood.
Fresh blood upto 3 days old is more likely to have viable white cells and has been to shown to have
greater chances of inducing Graft Versus Host Disease-a life threatening complication of blood
transfusion. Fresh whole blood is a vestige of past transfusion practices when appropriate
components were not available. American association of Blood banks has no indication for
whole blood transfusion in modern medical practice.
Causes of anemia
1> Increased red cell loss
v Acute: trauma / surgical / obstetric haemorrhage
v Chronic blood loss: GIT / urinary tract / reproductive tract / parasitic infestation /
malignancy / inflammatory / hemolytic disorders
2> Decreased production of red cells
v Nutritional deficiency – iron / B12 / folic acid / malnutrition
114
v Bone marrow failure
v Renal failure (decreased erythropoietin production)
v Chronic illness
v Lead poisoning
v Increased destruction of red cells
v Infections – bacterial / viral / parasitic
v Hemoglobinopathies
v Drugs-dapsone
v HDN
Acute Anemia
It is the result of acute blood loss – surgical / traumatic
v Acute Blood Loss
v Blood Vol decreased
v Total Hb is decreased
v O2 storage / transport / delivery decreased
Decreased Hb X Decreased O2 saturation X Decreased Cardiac output = Diminished O2
supply to tissues in acute anemia.
v Compensatory mechanism activated:
v Restoration of plasma Volume
v Restoration of Cardiac out put.
v Stimulation of ventilation
Chronic anemia
v Continued blood loss - small quantities.
v Nutritional deficiency
v Hemoglobinopathies
v Increased demand for red cells
v Pregnancy / Lactation
COMPENSATION
v Cardiac output increased
v O2 dissociation curve of Hb shifts to increase O2 release
v Fluid retention
Decreased Hb X Increased Saturation X Increased Cardiac Output =Maintains O2 supply to
tissues.
115
Management of Acute Anemia
v Treat underlying cause(Iron/B12 etc)
v Assess degree of oxygenation
v Improve O2 supply if needed.
v Transfuse ONLY RED CELLS, not whole blood, when O2 supply is inadequate.
v Transfusion in megaloblastic anemia: Dangerous because of the co-existent poor
myocardial function which could precipitate heart failure.
v Immune anemias: Antibodies in patient's serum may hemolyse not only transfused red
cells but patient's own remaining red cells.
Management of Chronic Anemia
v Exclude hemoglobinopathy
v Identify & correct blood loss: Local bleeding / helminthic infestation.
v Oral iron / B12 / folic acid
v Consider and treat malaria
v Review drug history – NSAIDS / Dapsone / anticoagulants / marrow suppressive
drugs
Treatment of Severe decompensated Anemia
v Treat infections
v Give O2 by mask
v Correct fluid balance
v Transfuse red cells in the right dose along with a diuretic like frusemide.
v It is not necessary to restore the normal Hb.
v Raise it just enough to relieve the clinical symptoms (usually 8g/dL is sufficient).
RED CELLS: When to Transfuse
ACUTE BLOOD LOSS
The primary treatment of acute blood loss is not blood. It is crystalloids / colloids.
Upto 20% Blood loss
v Give Crystalloids - Normal Saline / Ringer Lactate.
v Volume needed for replacement is 2-3 times the volume lost.
v Anticipate risk of fluid overload.
Continued loss
v Add colloids - 5% Albumin or hydroxyethyl starch.
v Replace colloids volume for volume
v 30 % Blood loss:
116
v Use red cell concentrate (packed red cells) to correct volume & oxygenation.
v If there is uncontrolled bleeding and laboratory evidence of coagulopathy – add fresh
frozen plasma.
v If bleeding continues - consider platelets after investigations.
v Use appropriate blood group switches when same group is not available.
THRESHOLD FOR RED CELL TRANSFUSION:
Historical Facts
v MAYO CLINIC in 1900 proposed a target value of 8-10 g/dL.
v CURRENT PRACTICE (NIH Consensus) is 7g/dL in the absence of disease 8-10g/dL in
the presence of disease (cardiovascular disease / risk factors / elderly).
Rate of fall of Hb is more important than the actual Hb value
Healthy individuals tolerate Hb levels as low as 5g / dL
RELATIVE EFFICACY
Whole Blood Red cells
v Volume 350 ml 250 ( 350ml with Additive solution)
v Haematocrit 40% 75%
v Red cell volume 160ml 190 ml
v Increase in Hb% 1g/dl 1. 3g/dl
v Unwanted plasma Plenty Minimal
v Platelets None None
v Complications More likely Less likely
v Cost More Less
LEUKO-DEPLETED RED CELLS : Why to use ?
v Avoids treatment of multiple febrile transfusion reactions.
v Prevention of CMV transmission
v Prevention of allo-immunisation to leukocytes and platelets
LEUKO-DEPLETED RED CELLS: When to use ?
v Multiply transfused patients.
v Multiparous women
v Intrauterine transfusions
v Exchange transfusions in newborn
v Haemoglobinopathies-Thalassemia
117
v Bone Marrow Transplantation
v Leukemias,Solid tumours, other immunodeficiency states
MASSIVE TRANSFUSION
v Replacement of patient's blood volume in 24 hrs.
v Transfusion of >20 units of red cells in 24 hrs.
v Replacement of >50% of patient's blood volume in 3 hrs.
v Replacement for blood loss >150ml/min in an adult.
POTENTIAL COMPLICATIONS:
v Thrombocytopenia
v Coagulopathy
v DIC
v Hypocalcemia
v Hyperkalemia
v Metabolic acidosis
v Hypothermia
THERAPY: Correct thrombocytopenia with platelets and coagulopathy with FFP.
Cryoprecipitate may be used to replace fibrinigen or factor VIII. Warming of blood is indicated
only in case of massive red cell transfusions.
Modifications of routine practice can minimise the need to transfuse red cells,
v Checking for and correcting anaemia before planned surgery.
v Stopping anti-coagulants and antiplatelet drugs before planned surgery
v Minimising the amount of blood taken for laboratory samples.
Current Transfusion Trigger for Red cells
v Local guidelines are important; local factors must be taken into account.
v Large randomised clinical trial ( Level I evidence) in critically ill patients demonstrated that a
restrictive transfusion policy : aimed at 70-90 g/l is at least equivalent, and possibly superior,
to a liberal policy maintaining Hb at 100-120g/l.
v In patients without cardiovascular disease, esp. younger patients, maintain haemoglobin
levels in the range 70-90 g/l.
v In patients known to have or likely to have cardiovascular disease, (hypertension / diabetes
/ elderly), maintain haemoglobin in the range 90-100g/l.
118
GENERAL GUIDE: In normal healthy individuals, a transfusion threshold of 70g/l is
appropriate. (critical level of 40-50g/l)
Transfusion In Obstetric Hemorrhage
v Monitor CVP and arterial pressure.
v Take samples for transfusion and coagulation screen. Order at least 6 units of red cells.
v Do not insist on cross matched blood if transfusion is urgently needed.
v Warm the resuscitation fluids.
v Transfuse red cells as soon as possible. Until then: - crystalloid, maximum of 2 litres -
colloid, maximum of 1.5 litres
v Restore normovolaemia as priority, monitor red cell replacement with haematocrit or
Hemoglobin. Note that the correct increment can be obtained only 24 hours post transfusion
in case of red cell transfusion and 1 hour post transfusion in case of platelets.
v Use coagulation screens to guide and monitor use of blood components
v If massive bleeding continues, give FFP 1 litre, cryoprecipitate 10 units while awaiting
coagulation results. Cryoprecipitate will need to be repeated twice a day till bleeding is
under complete control.
Appropriate use of Blood components in bleeding patient
FFP: indications and dose for haemorrhage
v More than 1 blood volume replaced or Prothrombin time prolonged with INR >1.5
and/or continued blood loss
Dose: 15 ml/kg or 1 Litre (4 packs) for adult of 60 kg
Platelets: Indications and dose for haemorrhage
v Platelet count below 50 × 109/l (<50,000/ul or cmm), in the presence of bleeding.
v In the absence of bleeding and or fever and if there is no planned invasive procedure a
platelet count of 10,000/ul or cmm is acceptable. Drop in Platelet below this level necessitates
transfusion with platelet concentrates.
v Dose: 4-6 platelet concentrates or one unit of single donor(apheresis) platelets.
Cryoprecipitate: Indications and dose for haemorrhage
v Useful only if the fibrinogen is particularly low(<1g/l) or <100mg/dl.
v Early use of FFP may avoid the need for cryoprecipitate
v Give 10 units initially and repeat based on fibrinogen estimation
v Note: Cryoprecipitate is not available from all blood centres. 5 units of FFP (1000-1250 ml)
contains, typically, the same quantity of fibrinogen as 10 units of cryoprecipitate
(approximately 150-250 ml)
v Dose: one unit/5 kg body weight or 10 units in the adult.
119
Intrauterine Transfusion for correction of pre-natal anemia Foetal distress is diagnosed by
diminished middle cerebral artery blood flow detected by ultrasonography. Rising atypical(anti-
D) titres coupled with foetal distress also constitute an ominous sign.
Management :
Transfuse red cell concentrate of group O Negative to achieve the desired target Hb level.
Red cells used for transfusion must have a hematocrit, as high as possible, preferably 90%,
although in practice, blood banks can seldom concentrate red cells beyond a hematocrit of 80%.
Red cells must be sickle cell negative and also negative for CMV infection.
CMV negative blood is difficult to find in our country where majority are exposed to CMV
infection, at some point in their lifetime. An alternative is to use Leukofiltered red cells. Red cells
must be filtered using a “leukodepletion filter for red cells”, which is able to remove more than
99.99% of leukocytes and the CMV within them. Filters are expensive costing about Rs1200/-but
well worth preventing CMV infection in the foetus.
Red cells used for IUT must also be irradiated with Gamma rays (Dose 25 Gy or 2500 rads) to
prevent post transfusion GVHD. Use of buffy coat removed or washed red cells is an inexpensive,
but much less effective alternative to leuko filtration. It is only effective in prevention of febrile
transfusion reactions, not in prevention of CMV infection.
It is desirable to use red cells less than 7 days for prevention of hyperkalemia and acidosis in case
of IUT and neonatal exchange transfusion. This is perhaps the only genuine exception for using
fresh blood in transfusion practice.
Time limits for infusing blood components :
All blood components must be transfused as soon as they are received from the blood bank
without warming them. All blood and blood components must be transfused at the same
temperature at which they are issued without warming. Warming of blood using water baths,
pillows, leaving at room temperature for 30 minutes are all equally erroneous.
Massive transfusion in the adult and exchange transfusion in the newborn are the only exceptions.
Blood is warmed using a blood warmer in these conditions.
Ordinarily one unit of red cells / whole blood must be transfused in 2 hours, never beyond 4
hours. Fresh Frozen Plasma being more fluid, may be transfused over 20-30 minutes after
thawing at 37 C in a sterile water bath. Likewise, cryoprecipitate and Platelet concentrates may be
transfused quickly over 20-30 minutes. It is important to use a new standard blood filter (clot
screen filter) with a pore size of 170 microns for transfusion of red cells / whole blood. The same
filter needs to be used for platelets, FFP and cryoprecipitate as well. Transfusions must be
documented and monitored at start of transfusion, 15 minutes post transfusion and finally at the
completion of transfusion.
More frequent monitoring may be necessary in case of sick patients.
120
In emergencies, the following may be used:
v Uncrossmatched group specific blood
v Cells - group “O” of appropriate Rh type
v Plasma – group “AB” (which lacks antibodies)
Conclusion: Anemia and blood loss are very common in women. Transfusion trigger for red cells
in the absence of cardiovascular risk factors (hyperetension / diabetes / elderly) is 7g/dl. In
presence of this, transfuse to maintain a higher level 8-9g/dl.
Platelets need to be given only when the count falls below 10,000/ul in asymptomatic patients.
However, in the presence of bleeding or planned invasive procedure, a count of 50,000/ul is
desirable. Use of FFP in coagulopathy in the absence of bleeding is guided by prothrombin time
and use of cryoprecipitate by fibrinogen levels. Fresh whole blood is not a substitute for blood
components. Avoid fresh blood and relative's blood to prevent GVHD. Transfuse blood without
warming using a filter within a maximum time of 4 hours. Even tested blood is not safe. Rational
use of blood is therefore recommended. Consent for transfusion of blood / refusal of transfusion
along with alternatives offered needs to be documented.
References:
1. Transfusion Medicine ,Volume 13 Issue 1 Page 17 - January 2003 T. J. Bray, P. Salil, H. A.
Weiss, J. D. H. Porter (2003). Transfusion medicine in India: a survey of current practice
2. Policy Barriers Preventing Access to Emergency Obstetric Care In Rural India
Dr Dileep V Mavalankar.,Public Systems Group,Indian Institute of Management, Ahmed)
3. Obstetrics & Gynecology 2004;104:1000-1004
4. Modern Blood Banking and Transfusion Practices, Denis M harmening
5. Transfusion Medicine, Jeffrey McCullough.
6. Technical Manual, AABB
7. BCSH guidelines for transfusion triggers.
8. Shivaram C, Guha's Textbook of Neonatology.
1 12
CONSENT FOR DIRECTED DONATION
1. I have been informed that transfusion between first degree relatives carries with it the risk of
a fatal (life threatening) complication called Post Transfusion -Graft Versus Host Disease.
2. I am also told that although rare (incidence 0.1 % or one in 1000 transfusions) this
complication is more likely to occur with relatives' blood, and is almost always fatal and
treatment for this is almost non-existent.
3. In light of this, I have been counseled by the blood bank staff named below, NOT to use
relatives blood. I have fully understood the risk of GVHD.
4. Further, I have weighed the risks of contracting HIV/ Hepatitis from an unknown donor in
the window phase/incubation period versus Post-Transfusion GVHD from a relative donor.
I understand PT-GVHD is more likely to be fatal than HIV/Hepatitis resulting from blood
transfusion.
5. Despite knowing all this, I still prefer that I / my patient receive blood from our relative only.
This has been explained to me in (language)________________________
I shall not hold the Blood bank/consultants/hospital responsible in the event of my/ my patient's
death due to post transfusion Graft Versus Host disease.
Signature: Sign of Blood bank Staff
Relation to patient Name of staff:
122
Anaemia in Pregnancy-A teaching hospital experience
Dr. K . V. MaliniM.D., D.G.O., MICOG, PGDMLE,
Professor, Dept of Obstetrics and Gynaecology,Bangalore Medical College, BANGALORE.
Anaemia is the most neglected and the commonest medical disorder seen in pregnancy. It has a
varied prevalence, etiology and degrees of severity in different populations, being more common
in developing countries. This nutritional problem keeps the woman in high risk category as she is
prone for many complications like PIH, sepsis, prematurity & low birth weight babies( Tyagi et
al1985). Several studies have reported association of anaemia with maternal and foetal morbidity.
This study is undertaken to assess the magnitude of the problem and its impact on maternal and
foetal outcome.
Material and Methods
A retrospective cohort study was conducted in Vani Vilas Hospital attached to Bangalore
Medical College, a premiere teaching institute. It is a 450 bedded referral maternity hospital
catering to the needs of population comprising mainly of low socio-economic group. The study
was undertaken for a period of three months from October – December 2006 and comprised of
retrospective analysis of 1380 singleton pregnant women admitted in labor with anaemia.
Women with multiple pregnancies and antepartum haemorrhage were excluded from the study.
The information regarding age, parity, level of Haemoglobin were collected from the records.
Haemoglobin was estimated by Sahli's method in our institute. Whenever complete haemogram
and stool examination were done, the reports were noted down.
Women were categorized into mild, moderate, severe and very severe group depending on Hb
percentage as per ICMR guidelines, i.e., mild – 10.9 to 10gm, moderate – 10 to 7 gm, severe - < 7gm
and very severe - < 4gm. Various maternal and foetal complication were studied under these four
groups. Standard Normal Variate test (Z Test) and Chi-square test were applied to the
complication observed under these groups.
Observations
The prevalence of anemia among obstetric admissions in our study was 52% (1380 / 2654). Out of
1380 women with anaemia, only 423 were booked and 957(69.4%) were unbooked. Most of the
women belonged to low socio-economic status. The commonest type of amaemia was Iron
deficiency anaemia as evidenced by the peripheral smear.
123
Most of the women belonged to moderate group as shown in the graph below.
Anaemia was more common in multi parous women as compared to primis.
Most of them were in the age group of 20 – 29 years
Various complications noted were :
Mild (426)
Moderate (810)
Severe (132)
Very Severe (12)
Distribution of casesn =1380
10% 1%
30%
59%
Parity n = 1380
Primi (588)
Multi (782)
57%
43%
Age distribution
Age in years
< 19 174
Number of cases Percentage
13%
20 - 29 1125 82%
30 and above 81 5%
Complications Mild Moderate SevereVery
SevereTotal
PTD 114 21 135
IUGR 45 12 279222
Birth Asphyxia 3 126 3
MSAF 3 6030 27
IUD 3018 12 1
PIH 129111 126
PPH 31 2
Forceps delivery 241212
CCF 1 1
Sepsis 1 1
Maternal Death 1 21
124
Foetal complications like low birth weight (< 2.5kg) babies, preterm deliveries, MSAF, birth
asphyxia, intrauterine deaths and maternal complications like pregnancy induced hypertension
were all seen more in severe and very sever anaemia group as shown in the graphs below.
0%
5%
10%
15%
20%
25%
30%
35%
Mild (80)
Moderate (149)
Severe (46)
Very Severe (4)
Low Birth Weight Babiesn =279
0.00%
5.00%
10.00%
15.00%
20.00%
Mild (31)
Moderate (86)
Severe (16)
Very Severe (2)
PreTerm Deliveriesn = 135
0%
1%
2%
3%
Mild (3)
Moderate (6)
Severe (3)
Very Severe (Nil)
Birth Asphyxian = 12
1%
2%
0%
2%
6%
8%
10%
12%
14%
16%
Mild (5)Moderate (40)Severe (13)Very Severe (2)
MSAFn = 60
18%
4%
0%
2%
6%
8%
10%
12%
14%
16%
Mild (3)Moderate (20)Severe (5)
Very Severe (2)
Intra Uterine Deathn = 30
18%
4%
0%
2%
6%
8%
10%
12%
14%
16%
Mild (25)Moderate (80)Severe (23)Very Severe (1)
PIHn = 129
18%
4%
125
There were three cases of atonic PPH, seen in severe and very severe anaemia group. Number of
forceps deliveries were also more in severe anaemia group. There were two maternal deaths, one
as a result of CCF and the second due to sepsis.
Discussion
From our study, it is evident that anaemia is still widely prevalent and is the commonest
preventable medical disorder found in pregnancy. The global prevalence in non-industrialized
countries varies between 35-75%, average being 56% (WHO in 1997). In our study, the prevalence
was 52%. The relative prevalence of moderate and severe anaemia in our study was almost
comparable with ICMR data. But, the number of mild anaemia cases were more in our study and
the number of very severe anaemia cases were more in ICMR study.
Quite a significant number of women were 19 years and below (13%).
Most of the women belonged to low socio-economic status and were unbooked. Nutritional
deficiency was the commonest cause. There were no haemolytic anaemia or
haemoglobinopathies in our study during this study period.
Though severe and very severe anaemia cases formed a small group, most of the maternal and
foetal complications were seen in this group. Since complications were many and each patient
had more than one complication, Standard Normal Variate test (Z Test) and Chi-square test were
applied to all the complications seen in mild and moderate anemia groups and sever and very
severe anaemia groups. It if found that all the complications were higher in the latter group. (Here
p = 0.708)
SE of p = (√pq)/n = (√0.7 x 0.3)/1380 = 0.0123
i.e., Z = (p – P)/((√pq)/n) = (0.708 – 0.5)/0.0123 = 16.26
0%
1%
3%
4%
5%
6%
7%
8%
Mild (6)Moderate (14)Severe (3)Very Severe (1)
Forceps Deliveryn = 24
9%
2%
Groups
Mild 13 %
ICMR Our Study
30 %
Moderate 57 % 59 %
Severe 12 % 10 %
Very Severe 18 % 1 %
126
which is much more greater than 3. hence, it can be firmly stated that all the complications were
dependant on severity of anaemia and more in women in severe or very severe anaemia group.
There were total of 10 maternal deaths during study period, out of which two were due to
anaemia. One patient died as a result of CCF secondary to severe anaemia and other died due to
sepsis with very severe anaemia. One of our patients had severe infection of episiotomy wound.
Her Hb% at admission was 4.2gm. She also had term IUD. Surprisingly in our study, there were
no wound infections following LSCS. May be because of blood transfusion before and after
surgery.
ConclusionIn spite of the advances in medicine, and development of modern technologies, nutritional
deficiency anaemia continues to be the major health problem looming large over pregnant
women in developing countries like India.
The fact that most of the women were unbooked proves that either our women are ignorant about
antenatal care or not having access to it.
The incidence of anaemia can be decreased by maternal health education. Importance of
antenatal care should be adequately stressed even if this means campaigning on a door-to-door
basis. 'Catch them Young' i.e., efforts to identify and treat anaemia in the adolescent age group
through school health programmes would be a better idea. Training and motivation of health
workers could go a long way in early detection and treatment of this preventable, social malady at
the grass root level.
Acknowledgement
Dr. Parvathi, Dr. Nirmala, Dr. Saraswathi for assisting in collecting the material.Mr. Joshi – Statistician, Community Medicine Department, BMC Bangalore.
References
v Kishore singh et al-j obst.Gynaec.India.569:45:1995
v Koen MC et al – J obst.Gyanec .India.569:45:1995
v Preety pandya-j.Obst .Gynaec. India.569:45:1993
v Rangnekar AG - J.Obst .Gynaec. India.172.43.1993
v Rathnam.S.S. – Bhaskar Rao, S.Arul kumar -obst gynaec. for P.G.Vol.1 ii edition 1999
v Samir.A.R. International journal -obst .Gynaec. 1995
v Samir Roy – J .Obst .Gynaec. India.743.42.92
v Sharma J B – Nutritional Anaemia during pregnancy in non-industrialized countries,
Progress in Obstetrics and Gynaecology, Studd Vol 15, 2003
v Suresh Deshpande - J .Obst .Gynaec. India. 37:49:1999
v WHO 1997
127
Blood Banks
Dr. Swetha Arasu Dr. Teena Thomas
Church of South India Hospital
Bangalore
About blood donation:
1. Person above 18 years of age and over 45kgs. in weight can donate blood once in three
months.
2. A normal adult has five to six liters of blood in his/her body of which only 300 ml is used
during blood donation. This blood is replaced by the body within 24 to 48 hours.
3. No special diet, rest or medicine is required after blood donation.
4. The donor should not have taken any medicine in the last 48 hours.
5. The donor should not have contacted jaundice in the previous three years.
6. Every donor is given a medical checkup prior to donation to see if he/she is medically fit and
doesn't suffer from anemia, high blood pressure etc.
7. The donor cannot contract AIDS or any other disease by donating blood.
128
For information about negative blood group donors visit http://www.negativegroups.com
BLOOD BANK
M S Ramaiah Medical Hospital
PHONE NO WHOLE BLOOD
PACKED CELLS
FFP PLATELETS CRYOPRECIPITATE
23606545 / 23606524
Rs. 700/- Rs. 650/- Rs. 650/- Rs. 650/- Rs. 650/-
Narayana Hrudyalaya
27835000 / 27835001
Rs. 500/- Rs. 500/- Rs. 500/- Rs. 500/- Rs. 500/-
NIMHANS 26995000 / 26568121
Rs.300/- Rs.300/- Rs.300/- Rs.300/- Rs.300/-
TTK Blood Bank 25293486 / 25287903
Rs.700/- Rs.600/- Rs.600/- Rs.600/- Rs.600/-
Sagar Apollo Hospital 26536700 / 26536701
Rs.940/- Rs.600/- Rs.600/- Rs.600/- Rs.600/-
Victoria Hospital 26701150 Rs.500/- Rs.500/- Rs.500/- Rs.500/- Rs.500/-
KIMS 26673056 Rs.500/- with replacement
Rs.500/- Rs.500/- NARs.500/- with replacement
Manipal Hospital 25024224 Rs.850/- Rs.650/- Rs.650/- Rs.650/- Rs.650/-
Dr.Shivaji Rao's Blood Bank 22224044 Rs.800/- NA NA NA NA
Jeeva Voluntary Blood Centre 26707755 Rs.700/- NA
AB+ve: Rs.750/-
Negative grp: Rs.900/-
Rs.700/-
Rs.750/-
Rs.900/-
Rs.700/-
Rs.750/-
Rs.900/-
Rs.700/-
Rs.750/-
Rs.900/-
NA
NA
Grace Blood Bank 23336608 Rs.700/- NA NA NARs.700/-
Rs.500/- with replacement
Rs.500/- with replacement
B'lore Lions Service Blood Bank
22266807 Rs.505/- Rs.605/- Rs.605/- Rs.605/- Rs.605/-
Hosmat Hospital 25593796 Rs.850/- NA NA NA NA
Unique Blood Bank Centre 26709970 Rs.700/-
AB+ve: Rs.750/-
Negative grp: Rs.900/-
Rs.700/-
Karnataka Red Cross Blood Bank
22268435 Rs.500/- NA NA NA NA
Navarang Blood Bank & Diag Lab
23521233 Rs.700/- NA NA NA NA
Minerva Blood Bank 26574830 Rs.700/- NA NA NA NA
Life Care Voluntary Blood Bank
25567392 Rs.700/- NA
Akshaya Blood Bank 23523987 Rs.700/-
Rs.700/- Rs.700/- Rs.700/-
Rs.700/- Rs.700/- Rs.700/-
129
Transfusions for Anemia – Tread with Caution
Dr. Tanya, Dr. Srividya, Dr. Prakash K. Mehta
Bhagwan Mahaveer Jain Hospital, Bangalore.
Introduction : Anemia contributes to significant morbidity and mortality in India. Up to 80% of
Indian women are anemic. Factors contributing to anemia include nutritional deficiency in pre-
pubertal and pubertal age group, frequent child birth in reproductive age group and
menorrhagia in peri-menopausal age group .Among the management options blood transfusion
plays an important role. However, transfusions need to be given with care and caution. Here is a
case report of a patient who underwent hysterectomy for DUB.
Case : Mrs. X, a 35 year multipara was referred to Bhagwan Mahaveer Jain Hospital for tertiary
care with history of undergoing TAH for DUB four days prior to admission. Patient apparently
had no pre-operative or intraoperative complications. Postoperatively patient was transfused 1
pint O positive whole blood, following which she developed vomiting, breathlessness and
decreased urine output. Post transfusion a fall in Hemoglobin levels was noted and hence she was
transfused 2 more units or O positive whole blood. Patient's condition continued to deteriorate.
She became hypoxic and had renal failure following which patient was referred to our centre.
Patient is P2L2 with last delivery 15 years back and underwent tubectomy .She had menorrhagia
since 2 years. Her past and family history were not significant
On Examination : :General condition : poor, Afebrile, Pallor++, Heart Rate - 60/min ,Blood
Pressure - 140/90 mmHg, RR - 38/min SP02 84%, CVS : S1S2,RS : scattered b/l crepitations +,
P/A Soft wound healthy BS+ , PV - vault healthy, no bleeding PV. Catheter in situ – no urine
draining.
Patient was admitted to ICU. Investigations showed Hb 5.9gm%; PCV 18.4%; Peripheral smear –
features of Hemolysis, Blood urea 167 mg %; Serum Creatinine 2.6 mg%; Na 137 meq/l; K+ 3.4
meq/l; RBS 105 mg%, USG done revealed Normal study. A diagnosis of ARF and hemolysis due
to? transfusion reaction? sepsis considered. A search was made for the precipitating factor Based
on history & investigation reports, mismatched transfusion was considered to be a greater
probability. Samples were sent to blood bank for blood group investigations. On direct matching
the blood group was revealed as O positive. However, on reverse cross matching, she was found
to have Bombay blood group. In view of anuria and rising creatinine, patient was started on
hemodialysis. In view of extreme rarity of Bombay blood group, extreme difficulty encountered
in obtaining cross matched blood. Only 3 pints of blood could be arranged – one from BMJH
blood bank, one from Manipal and one from Mumbai. We could arrange only 3 pints of Bombay
Blood group for the patient. Patient was also given erythropoietin injections in view of limited
availability of blood and with a hope that if the patient survives for a week, then this could take
care of anemia. In spite of all measures, patient's condition continued to deteriorate; she
130
developed ARDS and needed ventilatory support. Patient developed Generalized Tonic Clonic
convulsions. CT scan revealed multiple hypodense lesions with hyperdense lesions in Left
Frontoparietal and right parietal region and gross edema -suggestive of venous infracts. Patient
was started on steroids & epsolin. 24 hours later patient arrested and in spite of following all
ACLS protocol, she could not be revived.
Discussion: Individuals with the rare Bombay phenotype (hh) do not express substance H (the
antigen that defines blood group O) on their red blood cells, and therefore do not agglutinate
(bind with) A or B antigens of the ABO blood group system. Instead, they produce antibodies to H
substance (which is present on all red cells except those of hh genotype) as well as to both A and B
antigens, and are therefore compatible only with other hh donors. This rare group was first
identified in Bombay and hence the name. Transfusion of 'O' group blood to these persons would
result in immediate red cell lysis because of the presence of anti H antibodies in the serum of
Bombay Blood Group patients. Therefore blood from only a Bombay Blood Group individual
should be transfused to a Bombay Blood Group recipient. Given that this condition is very rare to
begin with, any person with this blood group who needs an urgent blood transfusion will
probably be unable to get it, as no blood bank would have any in stock. In the above case
morbidity could have been prevented by avoiding blood transfusion. Adequate preoperative
correction of anemia by hematinics, avoiding blood transfusion for treatment of mild to moderate
anemia goes a long way to prevent such mishaps
References:
Handa V, Oza RM, Patel RZ, Zanzarukiya BB, Mukherjee RA. The Oh (Bombay
group)phenotype.J Indian Med Assoc. 1984 Dec;82(12):446-7.
The Bombay group
131
ANAEMIA AND PREGNANCY – CASE REPORT
Dr. Premila Phillips, Dr. Sandhya Toppo
Church of South India Hospital, Bangalore
CASE REPORT: Reporting a case of severe anaemia in a primi, 37wks and 5days gestational
age, with preeclampsia and intrauterine growth restriction in latent labour.
v Mrs. ST, a 22 year old, Primi, was referred to C.S.I. hospital, Bangalore on 24.11.06 with
complaints of amenorrhoea of 37 weeks, swelling and pain of both feet for the past 3-4
months and shortness of breath on exertion of 2 months, worsening gradually to
breathlessness even at rest. There was no history suggestive of impending eclampsia.
v She has had 4 antenatal checks at a private clinic.
v At 27 wks, she was treated for threatened preterm labour.
v At 30 wks, she was treated for UTI. BP recorded at that time was 130/90 mmHg.
v At 34 wks, she was started on Tab. Alphadopa 250 mg bd, but no record of BP available. Her
hemoglobin at 34 wks was 4.5 g/dL for which she was treated with oral iron. Her USG at 34
wks was reported as single live intrauterine pregnancy of 29 wks with moderate
oligohydramnios (AFI-6.5 cm). Placenta fundal and posterior in position. No obvious
anomalies. ? IUGR.
v At 37 wks. her BP was 180/80 mmHg. She was also pale and breathless and hence referred the
same day to our hospital.
v The patient does not give any history of menorrhagia or blood transfusions in the past.
ON EXAMINATION
She was moderately built and moderately nourished. She showed gross pallor, was breathless
and had puffiness of face and extremities. Her pulse rate was 112/min and BP 160/90 mmHg. Her
JVP and DTR were normal. Her cardiovascular systemic examination revealed a haemic systolic
murmur which was heard all over her precordium. On abdominal examination there was mild
abdominal wall edema. Uterus 32 wks size, relaxed, cephalic presentation and fetal heart sounds
were regular. On pelvic examination, cervix was 75% effaced and os 3 cms dilated with the vertex
at 0 station
INVESTIGATIONS
Hemoglobin 3.1g/dL
PCV 13.8%
Platelets normal
Peripheral smear revealed microcytic hypochromic anaemia.
Reticulocyte count was 3 %,
Total.bilirubin 1.16mg/dL suggesting mild haemolysis.
132
Serum.albumin was 1.7g/dL
S.Uric acid was 6.2mg/dL.
The renal function tests and liver enzymes were normal.
Urine showed albuminuria of 2+ and 50-55 pus cells/hpf .
Ultrasonogram: At 37 wks showed a single viable fetus corresponding to 31 wks. Total
anhydramnios with a expected fetal weight of 1550+/-135 gms.
NST – Reassuring.
MANAGEMENT
3 units of packed red cells were transfused and labor was accelerated with oxytocin. Liquor was
clear. II stage of labour cut short with outlet forceps because of poor maternal efforts and anaemia.
Prophylactic prostadin given at delivery of anterior shoulder. A male baby of 1.7kg with good
apgars was extracted. One unit of packed red cells and one unit whole blood transfused
postnatally. Post natal period was uneventful. BP was 130-150/80-100 mmHg on anti-
hypertensive medication and patient was discharged on the 5th day. Her hemoglobin was 8.7
g/dL at discharge. She was advised to continue oral iron, calcium, protein and antihypertensive
medication and return for follow-up after 3 days.
COMMENT
Anaemia as a factor in pregnancy and childbirth complication kills 585,000 women annually the
worldover. In India anaemia is the commonest medical disorder seen in pregnancy with an
incidence of 40-70%. 85% of Indian women are anaemic due to iron deficiency anaemia. It is a
major contributing factor for maternal / perinatal morbidity and mortality in our country.
Poverty, illiteracy and ignorance lead to malnutrition and in turn anaemia. Severe anaemia in
pregnancy is associated with a high incidence of pregnancy induced hypertension, intrauterine
growth retardation, intrauterine death and preterm labour. Education and elimination of poverty
would go a long way in eradicating this preventable disorder. Women in the reproductive age
should be advised regular antenatal checks, prophylactic haematinics and proper balanced diet
rich in bioavailable Iron.
133
PUBERTY MENORRHAGIA – A CASE REPORT
Dr. Arpitha Deepak Singh, Dr. Nita Vasisht,
Church of South India Hospital, Bangalore
CASE
v 19yr old, Miss Poornima has had her primary education and is a tele-caller by occupation
belongs to middle socio-economic status. She has two siblings aged 16 and 13yrs (sisters,
both studying). Her father is a driver by occupation and her mother is a housewife.
HISTORY OF PRESENTING ILLNESS
v Poornima presented to our hospital on 30-10-2006 with complaints of continuous
bleeding P/V since 30.09.2006. This was the first episode of abnormal menstrual
bleeding. For this, she sought medical help at a local clinic, where she was prescribed
hematinics only. Patient also gave history of loss of weight since one month, and related
the same to the excessive bleeding P/V. She had no H/O amenorrhoea prior to the
current menorrhagia cycle. She gave no history of giddiness / nausea / vomiting /
chronic cough / fever / loss of appetite / bleeding per rectum.
MENSTRUAL HISTORY
v Patient attained menarche at 13yrs of age. Her cycles initially were irregular and of the
pattern 1wk/5-6months, with a normal flow. Following this, she has been having regular
cycles, 4days/28-30days, with a normal flow, with no clots / dysmenorrhoea. Her last
menstrual period was on 30-09-2006.
PERSONAL HISTORY
v Patient is unmarried and not sexually active. Patient is a poor-eater as per her mother's
history. She had not been dewormed in the recent past. No history of previous surgeries
/ blood transfusion / tuberculosis / drug intake / bleeding disorders.
FAMILY HISTORY
v No similar history in the family. Her mother and the older of her two sisters have regular
and normal cycles. There is no history of bleeding disorders in the family.
ON EXAMINATION
Patient was moderately built, poorly nourished with a Height of 153cm, weight of 33kg, with a
BMI of 14.6. Her vitals recorded were, Temp: 98.6°F, Pulse rate: 100/min and BP: 120/80mm Hg.
Clinically breasts and thyroid were normal. No bruises / petechiae / pedal edema were found on
examination
134
v Pallor: +++ (Conjunctiva / tongue-pale)
v RS: Clear CVS: Flow murmur + JVP: Raised
v PA: Soft, no tenderness / organomegaly
v PV: Bleeding +
v PR: NAD
CLINICAL DIAGNOSIS
v 19ry old poorly nourished girl with severe anaemia (secondary to menorrhagia) in early
failure
INVESTIGATIONS
v Blood groping/typing: “O” Positive
v Hemoglobin: 3.4g/dl
v PCV: 12.1%
v TC: 5,600cells/cmm
v DC: P75%L24%E01%
v Platelets: 2.2L/cmm
v TSH: 1.75mcIU/ml
v BT: 2'30" CT: 12'
v Urine R/M: WNL
v Stool: No ova
v Ultrasonography: Uterus AV, measures 71 x 29 x 48mm, ET: 4mm
Myometrim-N
B/L ovaries N
PERIPHERAL SMAEAR
v Very pale smear showing a marked paucity of erythrocytes,
adequate platelets & somewhat scanty leucocytes
v RBC's are very anisocytic, anisochromic and mildly poikilocytic
with no visible hemoparasites
v A few, single Howel Jolly bodies are seen
v Macrocytes, microcytes, elliptocytes and abnormal shapes are
seen
v WBC's and platelets are morphologically unremarkable
v IMPRESSION: ANAEMIA, VERY SEVERE, CONSISTANT WITH SEVERE IRON
DEFICIENCY OR CHRONIC DISEASE, MILD LEUCOPENIA
135
FINAL DIAGNOSIS
v 19ry old malnourished girl with severe iron deficiency anemia, in early failure
TREATMENT GIVEN
v Tab. Tranexaemic acid 500mg 8th hourly x 3days
v Tab. Norethisterone 12th hourly x 21days
v Three units compatible packed cells transfused
v Oral iron x 3months
v Deworming done
v Patient counseling regarding condition and modality of treatment
v Health education regarding diet, general health measures
AT DISCHARGE
v Sense of well-being expressed by patient
v Repeat Hemoglobin: 9.6g/dl
LESSONS LEARNT
v Anaemia is the most common and treatable condition affecting all age groups, more so
the adolescents and pregnant women in our country
v Education and awareness regarding the condition and its prevention, a key factor in
changing the current scenario
v Regular health camps, regular ANC's to detect/investigate the condition early and treat
adequately, a must
v Golden rule to be remembered and to be reinforced…“PREVENTION IS BETTER THAN
CURE!”
136
Obstetric Catastrophe leading to anemia
Dr.Bhavana Mishra, Dr.Shah Prarthana, Dr. Prakash K. Mehta
Bhagwan Mahaveer Jain Hospital, Bangalore.
Introduction: Antepartum hemorrhage is still an important cause of maternal death in the
developing countries. The major risk of placenta previa is severe vaginal bleeding and
consequent morbidity related to hemorrhagic shock and prolonged hypotension. Placenta previa
is overwhelmingly a problem of parous women. While it occurs only once in 250 nullipara, it is
more frequent in grand multipara and women with previous cesarean delivery. Here is an
interesting case of BOH, previous LSCS with twin gestation and placenta previa.
Case : Mrs .Y , a 25 yr old G3P2L0D2, was referred to Jain Hospital at 26+5 wks with twin
gestation & APH. She presented to us on 15.12.06 with heavy bleeding per vaginum since that
morning associated with passing of clots and mild abdominal pain. She appreciated fetal
movements well.
Obstetric history: ML: 6 years, non consanguineous, G3P2L0D2 - G! : 4 yrs back, had jaundice
antenataly, vaginal delivery at term, baby died 2 hrs later, cause not known.
G2: 2 yrs back, H/O placenta previa & LSCS for IUD at 7th month. She had PPH and was
transfused 5 units of blood. G3: LMP: 12/6/06 EDD: 19/3/07. H/O spotting twice in the 2d
trimester, diagnosed as placenta previa. When she had the third episode, she was admitted to a
near by hospital where she was transfused one unit of whole blood and discharged.
On examination: Pallor ++, Tachycardia (HR- 110/min), BP 100/60 mmHg.
P/A examination vertical scar+, uterus 32 wks size, with multiple fetal parts, no scar tenderness.
FHR +/+. PS: Bleeding ++ Clots +.
NST: Reactive for both fetuses. Scan done to confirm diagnosis of placenta previa and estimation
of fetal weight. Hemoglobin: 7.2gm%. Patient underwent emergency LSCS in view of BOH,
previous LSCS, placenta previa with twin gestation after rescue steroiding and arranging for
blood. Lower segment thinned out and vascular. Placenta cut through and two male babies
weighing 870 and 850 grams extracted. Both babies shifted to NICU. The first twin had TEF Type
II and expired on fourth post natal day. The second twin was ventilated stabilized and finally
discharged at the end of 6 weeks.
Patient transfused 2 units of whole blood and repeat hemoglobin was 8.4gm% hence no further
transfusion given. She was discharged on day 6 with advice to continue haematinics.
Discussion: The dilemma we faced while managing this case was about the decision to go ahead
and deliver the babies. There were no records available regarding patient's previous pregnancies.
Considering her H/O previous neonatal death and IUD, a decision had to be made, especially in
137
face of bleeding placenta previa, twin gestation and anemia.
Adequate support from blood bank is pivotal in management of patients with late pregnancy
bleeding to avert maternal morbidity and mortality. Facilities for immediate cesarean section,
neonatal resuscitation and intensive care are critical for the management of such patients. Early
transfer of patients to a tertiary centre results in a better maternal and neonatal outcome.
Bibliography: Archibong EI, Ahmed el SM. Risk factors, maternal and neonatal outcome in
major placenta previa: A prospective study. Ann Saudi Med. 2001 May-Jul;21(3-4):245-7.
138
A CASE OF ANAEMIA DUE TO THYROID DEFICIENCY
Dr. Parimala Devi
CASE HISTORY:
Patient aged 32 yrs., P2 with 2 LSCS was often treated for anemia.
She underwent Cesarean Section for 1st pregnancy with preterm PROM as indication. She did
well in the postnatal period. However, she would always have excessive menstrual bleeding
lasting for 5 to 7 days and was treated symptomatically. Soon she dropped her hemoglobin and
was given iron supplements.
She got an IUCD inserted but got it removed within a few months due to menorrhagia.
She was pregnant again and underwent repeat LSCS. Post operative period was uneventful.
Soon she resumed periods. She again had menorrhagia and was put on progestogens. USG
showed normal study.
She never improved with routine line of management, and she became quite pale and blood
transfusion was given to correct hemoglobin.
Detailed biochemical test revealed THYROID DEFICIENCY and correction of the same
controlled the menorrhagia.
Patient improved dramatically.
KEY POINTS:
Anemia secondary to hypothyroidism is common.
About 10 – 12% of DUB is due to hypothyroidism.
It is therefore important to investigate a case of resistant anemia, for thyroid deficiency too.
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