SEMINAR OF ANAEMIA
(PHYSIOLOGY)
By Group 3
COMPOSITION OF BLOOD
1. Cellular Portion (45% of
total blood volume)
-Erythrocytes (RBCs)
-Leukocyes (WBCs)
-Thrombocytes
2. Fluid portion (Plasma, 55%
of total blood volume)
Erythrocytes
Biconcave Disk
Flattened
Flexible
Semi-permeable
membrane
Contains Antigen
(ABO & Rh) Blood
type
Anuclear
No Mitochondria
Erythrocytes
Life Span
100-120 days
FUNCTIONS
Transport O2
to tissues
Transport CO2
from tissues
Fate
Destroyed by
macrophage cells
(liver, spleen,
bone marrow)33% of RBC cell
mass consist of
hemoglobin
Normal Erythrocytes
Normal Value
Male : 4.32 – 5.72 X 1012 cells/L
Female : 3.90 – 5.03 X 1012 cells/L
Source : myoclinic.org/test-procedures/complete-blood-count/basics/results/prc-20014088
Hemoglobin
Consist of 4 Globin
Adult (HbA) : 2α & 2β
Fetal (HbF) : 2α & 2γ
1 Heme bound to each
globin
Hemoglobin Normal Values
Adults
Male
13.5 - 17.5 g/dL
Female
12.0 - 15.5 g/dL
Source : myoclinic.org/test-procedures/complete-blood-count/basics/results/prc-20014088
Children
Newborn
14 - 24 g/dL
Infant
9.5 – 13 g/dL
Pregnancy
11 – 12 g/dL
77% HbF (Newborn)
↓
23% HbF (after 4 month)
Hemoglobin Synthesis
Source : myoclinic.org/test-procedures/complete-blood-count/basics/results/prc-20014088
a and β genes
mRNAs
a and β globins chain
Haemoglobin
Succinyl CoA+ Glycine
Protophophyrins
Heme
Fe
Erythropoiesis
Primitive Hemopoietic Stem Cell (HSC)
Proerythroblast
Early normoblast
Late normoblast
Reticulocyte
Erythrocyte
Regulators of Erythropoiesis
• Erythropoietin (EPO)
Synthesis depends on the supply of
1. Iron
2. Folic Acid
3. Vitamin B12
Binds O2 in the Hb within PBC
For Thymine synthesis DNA formation
Normal cell division/maturation
Deficiency
↓Hb Production
↓Erythropoiesis
Stimulate proliferation of erythrocytes progenitor
cells & their differentiation into mature RBCs
Required for Folic acid function DNA formation
Normal cell division, maturation
Rate of Erythropoiesis
The Pathology: ANEMIA
By Group 1
Anaemia
Definition
WHO : ANAEMIA is a condition in which the number ofred blood cells or their oxygen carrying capacity isinsufficient to meet physiologic needs, which vary byage, sex, altitude, smoking and pregnancy status.
OXFORD : ANAEMIA is defined as low heamoglobin(Hb) concentration, and may be due either to a low redcell mass or increased plasma volume.
Source : www.who.int/topics/anaemia/en/
Reduction of Hb concentration below
normal
ANAEMIA
Female Adult : <11.5 g/dL
Male Adult : < 13.5 g/dL
2 years – puberty : < 11 g/dL
Newborn infants : < 14 g/dL
Types of Anemia
Based on Mean Cell Volume (MCV)
- Normal MCV : 76-96 fL (femtolitres)
Low MCV
MICROCYTIC
ANAEMIA
Normal MCV
NORMOCYTIC
ANAEMIA
High MCV
MACROCYTIC
ANAEMIA
Varying MCV
HAEMOLYTIC ANAEMIA
Low MCV
MCV < 80fLMCH <27pg
MICROCYTIC
ANAEMIA
Normal MCV
MCV 80 – 95 Fl
MCH > 27 pg
NORMOCYTIC
ANAEMIA
High MCV
MCV > 95 fL
MACROCYTIC
ANAEMIA
1. Iron-Deficiency
Anaemia
2. Thalassemia
3. Sideroblastic
Anaemia
1. Acute blood
loss
2. Anaemia of
Chronic Disease
3. Bone marrow
failure
4. Renal failure
5. Hypothyroidism
6. Haemolysis
7. Pregnancy
1. B12 / Folate
Deficiency
2. Alcohol excess /
Liver Disease
3. Reticulocytosis
4. Cytotoxics
5. Marrow
infiltration
6. Hypothyroidism
7. Antifolate drugs
(Phenytoin)
Source : Murray Longmore, Oxford Handbook of Clinical Medicine, 9th Edition, 2014.
MCV: 80 to 100fL
MCH: 27 to 31
picograms/cell.
CLASSICAL SIGN AND SYMPTOMS
SIGNS SYMPTOMS
Pallor Shortness of breath
Tachycardia (Compensatory Mechanism) Lethargic
Cardiac failure Weakness
Palpitation
Headaches
Angina pectoris
Confusion
MICROCYTIC ANAEMIA
Iron Deficiency Anemia (IDA)
Group 3
• Most common and widespread of nutritional disorder in the world
• Affecting large number of women and children in non-industrialized
country and virtually all industrialized nations.
• Half of pregnant women in the world estimated to be anemic (52% non
industrialized, 23% industrialized.)
Prevalence
Classification
based on WHO
Malay
N=135
Chinese
N=130
Indian
N=123
All
N=388
Anemia
(Hb < 12g/L)
16.4 20.6 26.4 20.9
Depleted iron
storage (ferritin <15
22.9 25.2 53.9 33.0
IDA
(Hb<12g/L+ferritin
<15 + MCV <80 fl
4.3 9.9 18.0 10.3
The prevalence of anaemia and IDA
among urban Malaysian women
Prevalence of anaemia, depleted iron stores and IDA
(Medicine UPM 2010)
WHO regions Children
(0-4years)
Children
(5- 14 years)
Pregnant
women
All
women
(15-
59years)
Men
(15-
59years)
Elderly
Africa 45 228 85 212 10 800 57 780 41 925 13 435
America 14 220 40 633 4 500 53 787 19 443 12 617
South East Asia 111 426 207 802 24 800 214 991 184 752 60 206
Europe 12 475 12 867 2 400 27 119 13 318 18 095
Eastern
mediteranian
33 264 37 931 7 700 60 196 41 462 11 463
Western pacific 29 793 156 839 9 700 158 667 174 400 78 211
Overall 245 386 541 284 59 900 572 540 475 300 194 029
Estimated prevalence of anaemia (1990-1995) by WHO Region based on
blood haemoglobin concentration (WHO)
Mariah a 17 year old student who has recently migrated from Australia to
Malta with her parents. She comes to you complaining of general fatigue and
occasional dizziness. Mariah has no significant past medical history and is not
any regular medicine. She does not drink alcohol or smoke. Her parents are
both healthy. On examination, she has strong peripheral pulses, and her
cardiovascular system examination is normal. BP is 115/75mmHg, pulse
90/min and BMI 19.5kg/m2. Mariah has pale skin, conjunctiva and nail beds.
Scenario
Poor Diet Intake
Pathophysiology& Causes of IDA
Loss Of IRON Stores (Depletion Of Hemoglobin Recourse)
Malabsorption
Increased demands
Chronic blood loss
• GIT : peptic ulcer, esophageal varices, aspirin ingestion,
stomach/caecum/colon carcinoma, hookworm, angiodysplasia etc.
• Uterine menstrual loss (Menorrhagia)
• Prolonged hematuria, hemoglobinuria,, pulmonary haemosiderosis ,self
inflicted blood loss (rare)
Chronic blood loss
• Prematurity
• Growth
• Pregnancy
• Erythropoietin therapy
Increased demands
• Gluten-induced enteropathy
• Gastrectomy
• Autoimmune (atrophic) gastritis
Malabsoprtion
• A major factor in many developing countries but rarely the sole cause in
developed country
Poor diet intake
• Brittle nails
• Koilonychia
• Atrophy of papillae of the tongue, painless glossitis
• Angular stomatitis
• Dysphagia ( Plummer Vinson syndrome)
• Pica
Sign and Symptoms of IDA
• Blood count and film
- microcytic (MCV< 80 fl) and hypochromic (MCH < 27pg) anemia
- Poilocytosis
- Anisocytosis
Investigation
Iron deficiency anemia, severe. Blood film.
The field displays virtually all hypochromic
cells with an exaggerated pale center (arrow)
Test Findings
MCV Reduced
Serum iron Reduced
Serum TIBC Raised
Serum ferritin Reduced
Serum soluble transfer receptor Increased
Iron in marrow Absent
Iron in erythroblast Absent
Investigation cont.
• Treat the underlying causes
• Oral iron – ferrous sulphate ( 200mg three times daily, a total of 180mg
ferrous iron ) /- ferrous gluconate (300mg twice daily , only 70mg ferrous
iron)
• Parenteral iron (for high iron requirement)– ferric hydroxide sucrose (
200mg )/ iron dextran/ ferric carboxymaltose
Management
THALASSEMIA
Group 1
DEFINITION & EPIDEMIOLOGY
DEFINITION
Hereditary disease (autosomal recessive) ;
Defective in synthesis of globin chain in thalassemia -> imbalance globin
chain production-> precipitation of globin chain within red cell precursor->
ineffective erythropoiesis.
CAUSES
Thalassemia is caused by
mutations in the DNA of cells that
make hemoglobin .
The mutations associated with
thalassemia are passed from
parents to children.
The mutations that cause
thalassemia disrupt the normal
production of hemoglobin and
cause low hemoglobin levels and a
high rate of red blood cell
destruction, causing anemia.
CLASSIFICATION
thalassemia
alpha
1 gene
deletion
2 gene
deletion
3 gene deletion
4 gene deletion
beta
major minor Intermedia
CASE SCENARIO
Adriana is a 7 –years-old who lives with her parents in a suburban community.
Her parents brought Adriana to the US from their homeland in Greece when
she was 1-year-old. At the age of 3, Adriana was in the 10th percentile for
height and weight, pale, and her Hb was 5.8 g/dl. Following further diagnostic
studies, she was diagnosed with beta thalassemia major. Over the cause of the
next 4 years, Adriana was hospitalized every 1 – 2 months, so she could be
transfused with pack red blood cell.
PATHOPHYSIOLOGY• α-thalassemia
primarily to gene deletion causing reduced α-globin chain synthesis
Since all adult haemoglobin are containing, α-thalassemia produces no change in
the percentage distribution of haemoglobin A, A2 and F. In severe form of α-
thalassemia, excess β chain may form a β4 tetramere called haemoglobin H.
• β-thalassemia
Defects that result in absent β globin chain is called as βᴼ
Reduced synthesis is termed β
SIGNS AND SYMPTOMSTYPES ( ALPHA THALASSEMIA) SIGNS AND SYMPTOMS
Four-gene deletion (Hb Barts) Pale, oedematous, enormous livers and
spleen (hydrops fetalis)
Three-gene deletion Moderate anaemia and splenomegally
Two-gene deletion Mild anaemia
One-gene deletion Normal
TYPES ( BETA THALASSEMIA) SIGN AND SYMPTOM
Thalassemia minor Anaemia is mild or absent
Thalaasemia intermedia -Moderate anaemia
- May varies depending on mutation
Thalassemia major -severe anaemia
-Failure to thrive
-recurrent bacteria infection
-hepatosplenomegaly
-bone expansion
-classical thalassemic facies
-jaundice
INVESTIGATIONS (Can Be Applied To Both Alpha & Beta)
• Complete blood count
– Hb, MCV, MCH low
– RBC increased
– Red cell distribution width (RDW) – normal
• Peripheral blood film
– Microcytic, hypochromic
– Target cells, basophilic stipling, ± nucleated RBC
Blood smear showing marked microcytosis, hypochromia, target cell, and anisocytosis.
Peripheral blood smear showing basophilic stippling
CONT
• Hb analysis
– HPLC – No Hb A at all, replaced by Hb F and A2
– Hb electrophoresis – will be further explain after
this
• DNA analysis – alpha and/or beta gene
• Family screening
CONT…
•Haemoglobin (Hb) electrophoresis test
• Blood test done to check the different types of Hb in the blood.
• It uses an electrical current to separate normal and abnormal types of Hb in the
blood. Hb types have different electrical charges and move at different speeds.
The amount of each Hb type in the current is measured.
• An abnormal amount of normal Hb or an abnormal type of Hb in the blood may
mean that a disease is present.
• Typical finding : HbA decreased or absent, HbF increase, HbA2 variable
CONT…
• The most common abnormal Hb are :
– Haemoglobin S. This type of haemoglobin is present in sickle cell
disease.
– Haemoglobin C. This type of haemoglobin does not carry oxygen
well.
– Haemoglobin E. This type of haemoglobin is found in people of
Southeast Asian descent.
– Haemoglobin D. This type of haemoglobin is present in some sickle
cell disorders.
COMPLICATIONS
•Iron overload.
People with thalassemia can get too much iron in their bodies, either from the disease
itself or from frequent blood transfusions.
Too much iron can result in damage to :
•Infection.
People with thalassemia have an
increased risk of infection,
especially to those who had
splenectomy.
• In cases of severe thalassemia:
• Bone deformities. Thalassemia can make bone marrow expand, which causes bones to
widen.
This can result in abnormal bone structure, especially in face and skull.
Bone marrow expansion also makes bones thin and brittle, increasing the chance of broken bones.
•Enlarged spleen (splenomegaly). Thalassemia is often accompanied by the destruction of a large number
of red blood cells, making spleen work harder than normal, causing it to enlarge.
Splenomegaly worsen anemia as it can reduce the life of transfused red blood cells.
If spleen grows too big, it may need to be removed.
•Slowed growth rates. Anemia can cause a child's growth to slow.
Puberty also may be delayed in children with thalassemia.
•Heart problems. Heart problems, such as congestive heart failure and abnormal heart rhythms
(arrhythmias), may be associated with severe thalassemia.
Sideroblastic Anaemia
Group 4
Aetiology (Hereditary)
Structural defect of ALA-S gene
Impairment of heme synthesis
Accumulation of iron in mitochondria of erythroblasts
A ring of iron granules seen in Perls’ stain
Aetiology (Acquired)
Malignant diseases
Benign conditions
Signs & Symptoms
•Shortness of breath
•Weakness
•Lethargy
•Palpitation
•Headaches
•Visual disturbances – due to retinal
haemorrhages
•In older pt , symptoms of cardiac
failure , angina pectoris or
intermittent claudication or
confusion may be present.
•Pallor of mucous membranes
•Tachycardia
•Bounding pulse
•Systolic flow murmur at apex
SignsSymptoms
Laboratory investigations
Full blood count
Red cell indices
Peripheral blood film
Bone marrow iron
Iron studies
*Presence of 15% or more of ring sideroblasts in bone marrow
Basophilic stippling seen in lead poisoning
Sideroblastic anaemia
Hb Low
MCV Usually low in congenital type but MCV often raised in acquired type
MCH Usually low
Serum iron Raised
TIBC Normal
Serum transferrin receptor Normal
Serum ferritin Raised
Bone marrow iron stores Present
Erythroblast iron Ring forms
Haemoglobin electrophoresis Normal
Management
Pyridoxine therapy
Removal of toxic agents
Folic acid therapyBlood transfusion + iron chelating
agent
• Other factors that have been implicated:– Bone marrow toxins retained in renal failure
– BM fibrosis secondary to hyperthyroidism
– Haematinic deficiency– iron, vit B12, olate
– ↑ red cell distribution
– Abnormal red cell membranes causing ↑ osmotics fragility.
– ↑ blood loss– occult GIT bleeding, blood sampling, blood loss during haemodialysis or b’coz of platelet dysf(x).
– ACE inhibitors(by interfering w control of edogenous erythropoietin release)
11/18/2015
Macrocytic Anaemia
Megaloblastic Anaemia
Group 1
Epidemiology
• In developing countries, the deficiency of vitamin B12 is
significant in Africa, India, and South and Central America
due to low intakes of animal products.
• In western countries, severe deficiency is usually caused by
pernicious anaemia.
• B12 deficiency is more common in the elderly because B12
absorption decreases in atrophic gastritis patients which is
common in the elderly.
Case Scenario A 70-year-old woman presented with progressive weakness and fatigue.
The symptoms had begun about a month earlier, and she no longer felt well
enough to do her housework or take her daily walk. She experienced shortness
of breath on exertion. Complete blood cell count (CBC) was performed and the
results were, hemoglobin, 5.4 gm/dL; mean corpuscular volume (MCV), 103
µm3 (normal 76-96) ; red cell distribution width (RDW), 19.8% (normal, 12%-
15%),
She had no history of recent bleeding, jaundice, fever, anemia, or heart
disease. She had not been exposed to medications (other than occasional
vitamins and aspirin) or toxins.. Findings on the physical examination were
unremarkable except for mild tachycardia at rest (96 bpm), a blood pressure of
146/84 mm Hg recumbent and 142/78 mm Hg standing, pallor. Neither the liver
nor spleen were palpable. The stool was negative for occult blood. A chest x-ray
was normal, and an electrocardiogram showed only sinus tachycardia. The
blood urea nitrogen (BUN) level was 15 mg/dL; glucose, 108 mg/dL; and total
bilirubin, 1.2 mg/dL (normal, <1.2). Electrolyte levels were normal. A sickle
cell preparation was negative. Low serum B12 was notedBlood Film was
ordered
Causes of Megaloblastic Anaemias
• Vitamin B12 deficiency
• Folate deficiency
• Abnormalities of vitamin B12 or folate metabolism (eg transcobalamine deficiency , nitrous oxide, antifolate drugs)
Pathophysiology of Vitamin B12
Vitamin B12 is cofactor for:
1) Synthesis of thymidine
2) Normal methionine synthesis
In their absence:
Cause inadequate DNA synthesis
Defective nuclear maturation
(Nucleocytoplasmic Ansynchrony)
Blockade in cell division
Leads to:
• Abnormal large RBCs and erythroid precursors (megaloblasts).
• Affect granulocyte maturation.
• Neurologic complication:- attribute to abnormal myelin degradation.
Vitamin B12 Deficiency
Causes of severe vitamin B12 deficiency1. Nutritional
– Inadequate intake– Vegetarianism
2. Malabsorption– Gastric causes– Pernicious anemia– Congenital lack or abnormality of IF– Total or partial gastrectomy– Intestinal causes: chronic tropical sprue, intestinal stagnant loop
syndrome, ileal resection, Crohn’s disease, fish tapeworm
Causes of mild vitamin B12 deficiency
• Malabsorption of B12
• Elderly
• Atrophic gastritis
• Severe pancreatitis
• Gluten induced enteropathy
• HIV infection or therapy with metformin
Pathophysiology of Folate
• Folate enter plasma as methyl THF.
• Methyl THF is a required in synthesis of thymidine thus, for DNA synthesis.
• Lack of folate cause :
– Inadequate DNA synthesis thus, abnormal large RBC synthesis.
Folate Deficiency
Causes of folate deficiency• Nutritional
– Especially old age, institutions, poverty, famine, special diets
• Malabsorption– Tropical sprue, gluten induced enteropathy, partial gastrectomy, extensive jejunal resection or
Crohn’s disease
• Excess urinary folate loss– Active liver disease, CCF
• Drugs– Anticonvulsants, sulfasalazine
• Excess utilization– Physiological
• Pregnancy, lactation, prematurity
– Pathological• Haematological disease (haemolytic anaemias, myelofibrosis)• Malignant disease: carcinoma, lymphoma, myeloma• Inflammatory diseases: Crohn’s disease, tb , RA, psoriasis, malaria
• Mixed– Liver disease, alcoholism, ICU
Clinical Features
• Onset – insidious/ gradually progressive sign and symptoms of anemia
• Mildly jaundice- excess breakdown of hb due to increase ineffective erythropoiesis
• Glossitis, angular stomatitis, mild symptoms of malabsorption with loss of weight
• Neuropathy (severe B12 deficiency)
• Neural tube defect in fetus (eg : encephaly, spinabifida)
• Increased melanin pigmentation
Glossitis : beefy-red and painful tongue
Angular stomatitis
Baby with neural tube defect (spina bifida)
From : Essential Haematology , 6th Edition
Investigation
• FBC: MCV > 98fL
• FBP : Oval macrocytic rbcs, hypersegmented neutrophils, pancytopenia
• BMA : hypercellular, large erythroblast, failure of nuclear maturation, giant
metamyelocytes (BMA is not mandatory in B12/folate deficiency)
• Increased serum unconjugated bilirubin, LDH
• Reduced serum/ red cell folate and B12 (mandatory test)
Treatment of Megaloblastic AnaemiaVitamin B12 deficiency Folate deficiency
Compound Hydroxocobalamin (B12) Folic acid
Route Intramuscular Oral
Dose 1000ug 5mg
Initial dose 6x1000ug over 2-3 weeks Daily for 4 months
Maintenance 1000ug every 3 months Depend on underlying
disease; lifelong theraphy
may be needed in chronic
inherited haemolytic
anaemias, myelofibrosis,
renal dialysis
Prophylactic Treatment
Given To:
Total gastrectomy
Ileal resection
Pregnancy, severe
haemolytic anaemias,
dialysis, prematurity
From : Essential Haematology, 6th Edition
Normochromic & Normocytic
Anemia
Group 1
Acute of Chronic Disease (ACD)• Common type of anaemia among pt with chronic inflammatory and malignant dz
• Causes of ACD :
– Chronic iflammatory disease
• Infections (pulmonary abcess, tb, osteomyelitis, pneumonia)
• Non infectious (RA, SE, CTD, sarcoidosis )
– Malignant disease ( ca, lymphoma, sarcoma )
• Sign and symptoms depends on underlying causes
• Not related to bleeding, haemolysis or marrow infiltration
• EPIDEMIOLOGY
Most common anemia amongst patients with chronic inflammatory and malignant disease.
2nd commonest anemia after IDA, worldwide.
CASE SCENARIO 1
A 72 - year – old man, previously healthy, presents with fever, chills, cough
and SOB. CXR shows a right – middle – lobe infiltrate. He is diagnosed
with pneumonia and admitted for iv antibiotics. Blood cultures
eventually grow Strep. Pneumoniae. By hospital day 3, he is afebrile but his
Hb is 10.5 g/dl, down from 12.4 g/dl on admission and 13.5 g/ dl 1 month
ago. He has no evidence of GI blood loss or overt haemolysis. Red cell indices
revealed a normocytic normochromic anaemia.
CHARACTERISTIC FEATURES
Anemia in chronic disease
MCV/MCH Normochromic normocytic anaemia or mildly
hypochromic (MCV rarely <75fL)
Serum iron Reduced
TIBC Reduced
Serum ferritin Normal/ raised
Bone marrow iron stores Present
Eryhtroblast iron Absent
Hb electropheresis Normal
• Pathogenesis-Key regulatory protein – hepcidin which is produced by liver
High levels of production are encouraged by pro-inflammatory cytokines, especially IL- 6.
Hepcidin binds to ferroportin on the membrane of iron exporting cells, and thereby inhibiting the export of iron from these cells into the blood
Iron remain trapped inside the cells in the form of ferritin, levels of which are therefore normal or high in the face of significant anaemia
• Treatment- treat underlying cause (eg. 60% RA patients).• Inhibition hepcidin and inflammatory modulator → block the inhibition of iron
transfer.
EXAMPLE- ANEMIA IN CHRONIC KIDNEY DISEASE(CKD)
• Anaemia is a complication of CKD whereby erythropoietin deficiency is the most significant cause.
• Insufficient or absent erythropoietin secretion results in normochromic, normocytic anaemia.
• The anaemia becomes more severe as the glomerular filtration rate progressively decreases.
Haemolytic Anaemia
HERIDATARY ACQUIRED
Loss Of Elasticity:Sickle Cell
Anaemiao Sickle cell disease is a group of haemoglobin disorder in which the
sickle β-globin gene is inherited.
o Homozygous sickle cell anaemia (Hb SS) is the MOST COMMON
o Doubly the doubly heterozygote conditions if Hb SC and Hb
Sβthal also cause sickling disease
o The abnormal red blood cells are rigid and crescent- like shaped
that can stuck in the blood vessels resulting in blocking of the
blood flow. Hence, distribution of the blood to supply oxygen to
all parts of the body might be impaired.
Hoffbrand, A., & Moss, P. (2006). Essential haematology (5th ed., p. 85). Malden, Mass.: Blackwell Pub.
Epidemiology
o It is believed that the sickle cell abnormal hemoglobin originated in
Africa, where it is most commonly encountered, while India is
considered as an additional place of origin. HbS is prevalent in
Middle East and Mediterranean countries, while population migration
has taken the gene to almost all regions of the world, including
Western and Northern Europe.
o About 7% of the global population carry non-functional hemoglobin
gene, with more than 500 000 affected children born annually. More
than 80% of these are born and live in the developing countries in the
world.
o More than 70% of them have a sickle disorder. A number of affected
children born in developing countries might be died, misdiagnosed,
receiving treatment or left untreated.
Causes Point mutation at 6th codon of β globin (Glutamate valine)
Pathophysiology
Clinical Features
1. Vaso-occlusive crises
The earliest presentation in the first few years of life is acute pain in
hand, and feet (dactylitis) dt vaso-occlusion of the small vessels.
Severe pain in the other bones occur in older children/adult. Fever often
accompanies the pain.
2. Anaemia
Hb range from 6-8 g/dL but acute fall in Hb level can occur owing
to :
• Splenic sequestration
• Bone marrow aplasia
• Further haemolysis
Kumar, P. (n.d.). Kumar & Clark’s clinical medicine (Seventh ed., p. 409, 410)
3. Splenic Sequestration
• Vaso-occlusion causes acute painful enlargement of the spleen
• Causing splenic pooling of RBC hypovolaemia circulatory
collapse death
4. Aplastic Crises
Caused by infection with Parvovirus B19 or Folate deficiency
Clinical Features (cont)
Long-term Complications
• AFFECT GROWTH AND DEVELOPMENT OF CHILD
– Short statue in young children (regain height by adulthood)
– weight not appropriate with age (below normal weight)
– Delayed sexual maturation (boy- no increase in testicular volume
by 14 years; girl- no breast development by 13 and a half years)
• BONE
– Common site for vaso-occlusive of small vessels.
• Avascular necrosis of hips and shoulders
• Compression of vertebrae
• Shortening of bones in the hands and feet.
• Osteomyelitis (by Staphylococcus aureus, Staphylococcus
pneumoniae, Salmonella)
Kumar, P. (n.d.). Kumar & Clark’s clinical medicine (Seventh ed., p. 410)
INFECTIONS
• Tissue susceptible to vaso-occlusive (Bones , lungs, kidneys)
LEG ULCERS
• Occur spontaneously (vaso-occlusive) or following trauma. Then become infected and resistant to treatment.
CARDIAC PROBLEMS
• Cardiomegaly, arrthymias, iron overload cardiomyopathy.
• Myocardial infarction due to thrombotic episodes.
NEUROLOGICAL COMPLICATIONS
• 25% of patient
• Transient ischemic attacks, fits, cerebral infarction, cerebral haemorrhage, coma.
• Strokes occur in about 11% of patient under 20 years of age.
• Most common finding is obstrustion of a distal intracranial internal carotid artery or a proximal middle cerebral artery.
Cholelithiasis
– Pigment stone as a result of chronic haemolysis
Liver problems
– Chronic hepatomegaly and liver dysfuction caused by trapping of sickle cells.
Renal. Chronic tubulointestitial nephritis.
Priapism.
– Unwanted painful erection as a result of vaso-acclusion.
– Impotence
Eye
– Background retinopathy, proliferative retinopathy, vitreous haemorrhages and retinal
detachment all occur
Pregnancy
– Impaired placental blood flow causes
• Spontaneous abortion
• Intrauterine growth impairment
• Pre-eclampsia
• Fetal death
Investigations 1. Complete blood count (CBC)
Anaemia (Hb range 6-8 g/dL)
High reticulocyte count (10-20%)
2. Blood films (feature of hyposplenic
and sickling
Sickle cells(arrowed) and
target cells.
Post splenectomy film with Howell-Jolly
bodies(arrowed), target cells and irregular
contracted cells.
Kumar, P. (n.d.). Kumar & Clark’s clinical medicine (Seventh ed., p. 410)
Investigations (cont)
3. Sickle solubility test
A mixture of HbS in a reducing solution
(sodium dithionite) gives a turbid apperance
because of precipitation of HbS
Normal Hb gives clear solution
5. The parents of the affected child will
show features of sickle cell trait.
Normal
Sickle cell trait
Sickle cell anaemia
Hb electrophoresis
4. Hb electrophoresis to confirm
diagnosis
Results shows : no Hb A, 80-95% Hb SS,
and 2-20% Hb F
Treatment
o Prophylactic –to avoid those factors known to precipitate crises, esp dehydration,
anoxia, infections, stasis to the circulation and cooling of the cell surface
o Folic acid (5 mg once weekly)
o Pneumococcal, haemophilus, and meningococcal vaccination and Hepatitis B
vaccine if transfusion is needed.
o Regular oral penicillin (should start at dx and continue at least until puberty)
o Crises –treat by rest, warmth, rehydration by oral fluid and/or IV normal saline
(3L in 24H)
–blood transfusion is given in severe anaemia
o Hydroxyurea (15-20 mg/kg) can increase Hb F levels and have shown to improve
the clinical course children/adults who are having 3 or more painful crises each
year
o For pain –analgesia at appropriate level should be given (NSAID, opiates or
paracetamol)
Hoffbrand, A., & Moss, P. (2006). Essential haematology (5th ed., p. 89). Malden, Mass.: Blackwell Pub.
1. Membrane defects : Hereditary
Spherocytosis• Most common in northern Europeans
Pathogenesis :-
• Vertical interactions between the membrane skeleton and the lipid bilayer of the red cell
• Loss of membrane because release of parts of the lipid bilayer that are not supported by the skeleton
• Normal biconcave red cell but become increasingly spherical as loss of surface area relative to volume as they circulate through spleen and the rest of RE system
• Unable to pass through splenic microcirculation where they die prematurely
Blood film of HS
Membrane defects : Hereditary
SpherocytosisMolecular basis :-
• Ankyrin deficiency/ abnormalities
• Alpha or beta – spectrin deficiency / abnormalities
• Band 3 abnormalities
• Pallidin (protein 4.2) abnormalities
Clinical features :-
• Autosomal dominant rarely recessive
• Anemia can be present at any age
• Fluctuating jaundice (particularly marked if a/w Gilbert’s disease (a defect
of hepatic conjugation of bilirubin) ; splenomegaly occurs in most patients
• Frequent pigment gallstones
Membrane defects : Hereditary Spherocytosis
Investigation :-
• A rapid fluorescent flow analysis of eosin-maleimide bound to red cells
• Treatment :-
• Splenectomy : preferably laparoscopic but only if clinically indicated
;symptomatic anemia/gallstones/leg ulcers/growth retardation – risk of
post-splenectomy sepsis particularly in early childhood
• Cholecystectomy should be performed with splenectomy if symptomatic
gallstones are present
Membrane defects : Hereditary
Spherocytosis
2. Defective red cell metabolism : Glucose-
6-phosphate dehydrogenase deficiency
Epidemiology :-
• 400 million people worldwide are deficient in enzyme activity
• Sex-linked
• Affecting males
• Carried by females (advantage resitance to Falciparum Malaria
• Main races :- West Africa, the Mediterranean, the Middle East and SE Asia
• Mildly in black Africans, more severe in Orientals and most severe in Mediterranean
• Severe deficiency occurs occasionally in white people
Agents that may cause HA in G6PD deficiency (Things that induce
OXIDATIVE STRESS) :-
• Infections and other acute illnesses eg DKA
• Drugs – antimalarials eg primaquine, sulphonamides eg cotrimoxazole,
analgesics eg aspirin, antihelminths eg beta-napthol
• Fava beans or other vegetables
• Miscellaneous eg vit K analogues
Defective red cell metabolism : Glucose-6-
phosphate dehydrogenase deficiency
Defective red cell metabolism : Glucose-6-
phosphate dehydrogenase deficiency
Pathogenesis :-
• Function of G6PD is to reduce nicotinamide adenine dinucleotide
phosphate (NADP)
• The only source of NADPH for production of glutathione
• Defieciency of G6PD renders the red cell susceptible to oxidant stress
• Most common types are B (Western) and type A in Africans
Clinical features :-
• Usually asymptomatic
• Main syndromes :-
1. Acute HA in response to oxidant stress eg drugs, fava beans or infections –
caused by rapidly developing intravascular haemolysis with
haemoglobinuria, the anemia maybe self limiting as new young red cells
are made with near normal enzyme levels
2. Neonatal jaundice
3. Rarely, a congenital non-spherocytic haemolytic anemia
These syndromes may result from different types of severe enzyme deficiency
Defective red cell metabolism : Glucose-6-phosphate dehydrogenase deficiency
Diagnosis :-
• Between crises the blood count is normal
• By screening test or direct enzyme assay on red cells
• During crises – ‘bite’ cells/ ‘blister’ cells / contracted and fragmented cells which have had Heinz bodies removed by the spleen. Heinz bodies are oxidized, denatured Hb
• Higher enzyme level in young red cells, red cell enzyme assay may give a ‘false’ normal level in the phase of acute hemolysis with a reticulocyte response
• Subsequent assay after the acute phase reveals the low G6PD level when the red cell population is of normal age distribution
Defective red cell metabolism : Glucose-6-
phosphate dehydrogenase deficiency
Treatment :-
• Stop offending drugs
• Treat underlying infection
• Maintain high urine output
• Blood transfusion for severe anemia when necessary
• Photography and exchange transfusion might be needed in severe cases for neonates as they are prone to neonatal jaundice. The jaundice is usually not caused by excess haemolysis but by deficiency of G6PD affecting neonatal liver function
Defective red cell metabolism :
Glucose-6-phosphate dehydrogenase
deficiency
Haemolytic Anaemia
HERIDATARY ACQUIRED
Group 4
Autoimmune Hemolytic anemia
A 32-year-old man gradually noticed that he had yellow eyes and dark urine, felt continually tired, and was short of breath when climbing stairs.
He had no other symptoms; in particular there was no itching, fever or bleeding, and he was not taking any drugs. On examination, he was anaemic and jaundiced.
He was afebrile and had no palpable lymphadenopathy, but evident of splenomegaly
Possible Diagnosis?
Possible causes Points
Liver disease JaundiceDark urineSplenomegaly
Hemolytic anemia JaundiceDark urineShortness of breathTired Splenomegaly
INVESTIGATION
FBC
• Haemoglobin 54g/l (130- 180 g/l)
• WBC 9.4 x 109/L
• Platelets 192 x 109/L
• MCV 120 fl (76-96 fl)
• Reticulocyte count 9% (<2%)
• The blood film shows gross polychromasia and spherocytes; Suspected :Hereditary spherocytosis
AIHA
FURTHER INVESTIGATION
• LFTs
Serum bilirubin 47 umol/L ( 3-17umol/L)
• LDH 5721 iu/L (105-333iu/L)
• DAT 3+ positive with IgG
.
PROVISIONAL DIAGNOSIS
Warm AIHA +ve DAT with IgG
Autoimmune hemolytic anemia
• Acquired disorder resulting from increased red cell destruction d/t red cell autoantibodies.
• Classification :• Warm AIHA
• Cold AIHA
• Paroxysmal cold haemoglobinuria (PNH)
Warm AIHA
• Autoantibodies predominantly IgG
• Possess relatively high affinity for RBCs at 37ºc
• Clinical Features• Occur at any age either sex
• Short episode of anemia and jaundice.
• Generalised symptoms –fatigue, weakness, malaise, fever
• Splenomegaly & hepatomegaly common
Cold AIHA
Autoimmune predominantly IgM
Antibody attach to red cells and cause agglutination – at lower temperature <4◦C
• Infection related : Mycoplasma. pneumonia, EBV
• Clinical Features
• Exacerbation in winter
• Cold, painful, often blue fingers, toes, ears or nose (Acrocynosis)
Paroxysmal cold haemoglobinuria (PNH)
• Due to a biphase IgG antibodyAttaches with complement to RCs in the cold extremities
• Causes lysis when the cell is warmed later from the complement which remains attached
• Post-viral phenomenon
• Typically an acute self-limiting disease
Clinical features PCH
• Presents acutely with leg and back pain, abdominal pain with cramps, nausea/vomiting/diarrhoea and
• dark urine (haemoglobinuria)
• following exposure to the cold
Investigation for suspected AIHA
• FBC and reticulocyte count
• Blood film
• DAT (Direct Agglutination Test)
• Donath Landsteiner Ab (test for PNH)
• Blood group specificity
• Cold agglutinin titre
• Tests for associated infection or disease
Treatment
• Corticosteroid (induced remission)
• Splenectomy (if fail to respond well to corticosteroid)
• Immunosuppressive drugs ( rituximab)
• Blood transfusion (if necessary)
• Avoidance of Cold ( Cold AIHA & PNH)
• Folic acid – as active hemolysis consume folate
Alloimmune Haemolytic
Anaemia
Classification(source : Essential Haematology Hoffbrand Moss)
Induced by red cell antigens
• Haemolytictransfusion reactions
• Haemolytic disease of the newborn
• Post stem cell grafts
Drug-induced
• Drug-red cell membrane complex
• Immune complex
Haemolytic transfusion reactions(source : Essential Haematology Hoffbrand Moss)
Immediate Delayed
Clinical features of a major haemolytictransfusion reaction
(source : Essential Haematology Hoffbrand Moss)
Haemolyticshock phase
Oliguric phaseDiuretic phase
Investigations (source : Essential Haematology Hoffbrand Moss)
Check for blood compatibility and
bacterial contamination of
the blood
Management(source : Essential Haematology Hoffbrand Moss)
To maintain blood
pressure and renal
perfusion
IV dextran, plasma or saline &
frusemide
IV hydrocortisone
& antihistamine
IV adrenaline
Compatibletransfusion
Drug-induced immune haemolytic anemia
Drug-induced immune haemolyticanemia
• Drug-induced immune hemolytic anemia is a blood disorder that occurs when a medicine triggers the body's defense (immune) system to attack its own red blood cells.
• Drugs can cause HA by 3 mechanisms.1)Antibody directed against a drug red-red cell membrane
complex – Penicillin, ampicillin2)Deposition of complement via a drug protein(antigen)-
antibody complex onto the red cell surface – Quinidine, Rifampicin
3)A true autoimmune hemolytic anemia with unclear role of the drug – methyldopa
Symptoms
• Dark urine
• Fatigue
• Pale skin color
• Rapid heart rate
• Shortness of breath
• Yellow skin color (jaundice)
InvestigationsPhysical examination : enlarged spleenTests : blood/ urine test- Absolute reticulocyte count- Direct or indirect Coombs test- Indirect bilirubin levels- Red blood cell count- Serum haptoglobin
Treatment
- Stop taking the drugs
-Take a prednisone to suppress
the immune response against
the red blood cells. Special
blood transfusions may be
needed to treat severe
symptoms.
Red Cell Fragmentation syndromes.
DEFINITION
• Form of haemolytic anaemia caused by intravascular mechanical trauma resulting in destruction of red cells, related to cardiovascular defects and haemolytic anaemia.
• Caused by red blood cells passing through abnormal small vessels with also fibrin deposition.
• Also known as microangiopathic hemolytic anemia.
• Also associated with disseminated intravascular coagulation or platelet adherence.
Infection-induced hemolytic anemia
Microorganisms may cause injury to red cells through different
mechanisms such as:
(1) physical invasion of red cells (e.g. malaria)
(2) hemolysin secretions(alpha toxin) to damage the red cells directly
(e.g. Clostridium perfringen)
(3) infection that triggers formation of antibody (anti-I) against red
cells (e.g. mycoplasma)
(4) microangiopathic hemolysis caused by disseminated intravascular
coagulation associated with infection.
(5) may precipitate haemolytic crisis in G6PD deficiency.
Anaemia in
infant & children
PAEDIATRICS TEAM:
Muhammad Faiz Bin Nordin
Bibi Afzarina Binti Mohamed Hanafee
Hanis Zahirah Binti Baharudin
Definition
Anaemia is defined as an Hb level below the normal range.
The normal range varies with age, so anemia can be defined as:
• Neonate : Hb < 14 g/dl
• 1-12 months : Hb < 10 g/dl
• 1-12 years : Hb < 11 g/dl
Causes of anaemia in infant & children
• Impaired red cell production
• Increased red cell destruction (haemolysis)
• Blood loss
• Anaemia of prematurity
Impaired red cell production
May be due to
Infective erythropoiesis- iron deficiency
red cell aplasia- Fanconi anemia
Infective erythropoiesis:Iron deficiency
• Main cause
- inadequate intake
- malabsorption
- blood loss
• Common in infants because additional iron is required for ↑ blood volume accompanying growth & to build up
• Diagnostic clue for infective erythropoiesis
- normal reticulocyte count
- abnormal MCV of RBC :
*low in iron deficiency
*raised in folic acid deficiency
• Iron may come from
- breast milk
*low iron content but 50% of iron is absorbed
- infant formula: supplement
- cow’s milk
*higher iron content than breast milk but only
10% is absorbed.
- solid introduced at weaning
Dietary sources of iron
Iron requirement during childhood
• Clinical feature- most infant & children are asymptomaticuntil Hb drop below 6-7 g/dl
- When it become worsen, children tire easily& young infant feed more slowly than usual.
- appear pale but pallor is an unreliable signunless confirmed by pallor of conjuctiva, tongueor palmar creases.
- children have ‘pica’
• Management- dietary advice and supplementation with oral
iron.*except for malabsorption (celiac disease) & chronic
blood loss patient (Meckel diverticulum)- should be continue until Hb is normal and then
for a minimum of a further 3 months toreplenish the iron stores.
- Blood transfusion should never be necessary fordietary IDA
Red cell aplasia
• Causes
- congenital red cell aplasia
*Fanconi anaemia
- transient erythroblastopenia of childhood
- parvovirus B19
• Diagnostic clue
- low reticulocyte count despite low Hb
- normal bilirubin
- negative direct antiglobulin test
(Coombs test)
- absent red cell precursors on bone marrow
examination.
Aplastic anaemia: Fanconi anemia
• Most common inherited type
• Autosomal recessive diorder due to genetic defect DNA repair.
• Usually oocur among 5 to 10 years old children.
• 10% developed acute myeloblastic anemia
• Clinical feature
- Growth retardation & congenital effect of
skeleton
- short stature, abnormal thumb and radii,
microcephaly, micropthalmia, café au lait &
hypopigmented spot, renal structural
abnormality
• Management
- bone marrow transplantation using normal
donor bone marrow from unaffected siblings
or matched unrelated marrow donor.
Causes of anaemia in infant & children
• Impaired red cell production
• Increased red cell destruction (haemolysis)
• Blood loss
• Anaemia of prematurity
Increased red cell destruction(haemolytic anemia)
• Causes
- red cell membrane disorders
*Hereditary spherocytosis
- red cell enzyme disorder
*G6PD deficiency
- haemoglobinopathies
*Sickle cell disease, B-thalassaemia major
red cell membrane disorders:Hereditary spherocytosis
• Autosomal dominant inheritance but 25% of cases there is no family history
• May cause early, severe jaundice in newborn infants.
• Clinical feature- usually asymptomatic- jaundice, anemia, mild to moderatesplnomegaly, aplastic crisis & gallstones
• Management - oral folic acid, splenectomy if symptomatic
red cell enzyme disorder:G6PD deficiency
• Commonest red cell enzymopathy
• Is x-linked recessive (predominantly affect male)
• May present with neonatal jaundice
• Causes acute intermittent hemolysis precipatated by infection, certain drugs, fava bean & naphthalene.
• Associated with jaundice, dark urine, fever, malaise
• Management
- parents should be given advice about the sign of acute
hemolysis and give a list of drugs, chemicals and food
to avoid.
Haemoglobinopathies:Sickle cell disease
• Autosomal recessive• SCD result in ischemia in organ• Clinical feature- anemia, infection, painful crises, squestration crises,
splenomegaly, growth failure, gallstone- Serious complication are bacterial infection, acute chest
syndrome, stroke and priapism.• Management - Treatment of acute crisis- oral or IV analgesia and good
hydration- Treatment of chronic problem- hydroxyurea to increase
HbF, bone marrow transplant
haemoglobinopathies:B-thalassaemia major
• Mutation of B-globin gene result in an inability to prodece HbA
• Clinical feature
- severe anemia, growth failure, pallor,
jaundice, bossing of skull, maxillary
overgrowth, splenomegaly, hepatomegaly,
need for repeated blood transfusion
• Management
- life long blood transfusion
• Complication of long rem-blood transfusion in children
- iron deposition
- antibody formation
- infection
Anaemia in the newborn
• Reduced RBC production
• Increased RBC destruction
• Blood loss
• Anaemia of prematurity
Blood loss
• Main causes
- feto-maternal haemorrhage
- twin-to-twin transfussion
- blood loss around the time of delivery
• Main diagnostic clue
- severe anemia with a raised reticulocyte
count and normal bilirubin
Anaemia of prematurity
• Main causes
- inadequate erythropoietin production
- reduced red cell lifespan
- frequent blood sampling whilst in hospital
- iron and folic acid deficiency (after 2-3
months)
Thank You
PHYSIOLOGICAL CHANGES IN PREGNANCY
ESSENTIAL FOR:
Support and protection to developing fetus
To prepare the mother for labour and delivery
CHANGES ARE DUE TO:
Hormonal alteration
Increased metabolic
Mechanical factor of gravid uterus
WHY STUDY THE CHANGES???
To differentiate normal from abnormal
To make the process of delivery smooth
To anticipate and manage complications
HEMATOLOGICAL SYSTEM
1) Plasma volume
o Begin to ↑ to 10% at 7 weeks and increasing rapidly, then plateauing at 40-50% by 32 weeks.
o At the same time,red cell volume also ↑ by 15-20% → help to improve utero-placental perfusion
2) Red cell mass
Red cell mass expansion < blood volume expansion
Total net of blood conc./viscosity ↓ by 20% (condition known as hemodilution)
Dilutional anemia(physiological anemia)
Oedema in pregnancy d/t drop colloid oncotic
pressure
3) Blood component
o ↑ total vol. RBC up to 25% d/t elevated level erythropoeitin →provide extra O₂ demand
o WBC can go up to 15,000-16,000/mm3
o Platelet slightly fall d/t dilutional effect
o ↑ clotting factors(VII,VIII,IX,X) and fibrinogen→protect from hemorrhage at delivery
• Severe anemia may weaken the uterine muscle strength which leads to uterine atony, that leads to post partum hemorrhage
• Anemia can also lower resistance to infectious disease
• However, the impact of anaemia on the extent of blood lost at childbirth and postpartum is not well-understood.
How ‘anemia’ cause increased risk of PPH ?
• Check ferritin in early pregnancy: give iron supplements only if iron deficient
• Folic acid 5mg daily is required.
• Parenteral iron should be avoided
• The aim during pregnancy is to maintain pre-transfusion Hb concentration level above 10g/dL
How do you manage a patient with thalassemia during pregnancy ?
• Thalassemia screening of the partner; If both positive, the couple need counselling on the risk of pregnancy with thalassemia major.
• Evaluation of cardiac function by ECHO, and of liver and thyroid functions, in each trimester (Main risk to the mother is cardiac complications).
• Iron chelation therapy is complex and should be tailored to the needs of the individual woman.
Others
Anemia in Pregnancy
Contents
Definition of anaemia in pregnancy
Prevalence of anaemia in pregnancy
Causes of anaemia in pregnancy
Iron-deficiency anaemia
- factors affecting Iron absorption
- types (Prepartum anaemia, IDA during Pregnancy, Anemia + Post partum hemorrhage)
- signs & symptoms of IDA
- advice on how to take Iron tablet
Definition of anaemia in pregnancy
During Pregnancy
Haemoglobin(g/dL)
WHO < 11
CDC < 11 (1ST trimester)
< 10.5 (2nd trimester)
< 11 (3rd trimester)
Post partum
Haemoglobin (g/dL) <10
Prevalence of anemia in pregnancy
World 47% 42% 30%
Malaysia 32% 38% 30%
Pre-school children Pregnant women
Non-pregnant women during
child bearing age
WHO Global Database on Anemia
Prevalence (contd.)
• Developing countries
– Africa 35% to 56%
– Asia 37% to 75%
– Latin America 37% to 52%
• Industralised countries- mean prevalence 18%
• HSNZ- 70.8%
Insufficient intake/insufficient production : nutrition, blood disease
Increase loss : bleeding, renal disease, infestation of parasites
Increase demand : placenta, fetus, red blood cells expansion
Causes of anaemia in pregnancy
Iron-deficiency Anaemia (commonest cause)
The most frequent nutritional disorder
How many suffer from iron deficiency anemia?
2 billion peoples
1/3rd of the world’s population
Factors affecting Iron absorption
Iron Absorption Enhancers
- Vitamin C; citrus fruit and juice, kiwi, strawberries, tomatoes, etc
Iron Absorption Inhibitors- Iron binding polyphenol: red wine- Coffee & tea- Eggs- Milk
Prepartum anemia
• Among fertile, non-pregnant women, ∼40% have ferritin of ≤30 μg/L(low iron status)
• Prepartum IDA predisposes to postpartum IDA- some amt blood loss during labour, lactation, dilutional effect of pregnancy
Test Level Remarks
Serum Ferritin (ug/L) < 30 Low iron status
< 15 Iron deficiency
IDA During pregnancy
Iron requirement in pregnancy
100mg/day iron for all
women*
9x higher
Iron requirement during pregnancy
Anemia and Post Partum Hemorrhage
• Anaemia increase the risk of PPH
• Unability of uterus to contract
• Risk of DIVC higher
• Risk of post partum hysterectomy higher
Post-partum Anemia
“More than 80 percent of maternal deaths are caused by haemorrhage,…… Most of these deaths are preventable when there is access to adequate reproductive health service”
Post partum anemia
• Severe postpartum anemia is a complication of 5% of deliveries
• Following delivery, women lose some amount of iron through breastfeeding and lactation
• IDA has been associated with impaired cognitive function and behavioral disturbances in postpartum women
• Mother’s iron status should be evaluated prior to discharge to monitor postpartum anemia
Post partum anemia
• Iron deficiency persists beyond the 4-6 weeks postpartum period
– 12% of women are iron deficient up to 12 months after delivery
– 8% of women are iron deficient 13-24 months after delivery
• Iron supplementation should continue after delivery if iron status remains low or while the mother is breastfeeding
Sign & Symptoms of IDA
HEADACHESCOLD HANDS
& FEET
WEAKNESS, FATIGUE,
SHORTNESS OF BREATH
DIZZINESSPALE SKIN
PALLOR
KOilonychia
ANGULAR STOMATITIS
ATROPHIC GLOSSITIS
CHEALITIS
Clinical sign of anaemia
Management of Anemia in pregnancy
Method Pros Cons
Oral Iron Cheap, Easy to take, Hardly any serious side effects
Slow to act, Compliance issue
Parenteral Iron Faster action, ensure compliance
Cause anaphylactic reaction, Pain and skin discoloration at injection.
Blood Transfusion Treat anemia almost instantly
Mismatch, Blood reaction, Disease(Hepatitis, HIV), Fluid Overload
• IDA is treated mainly with iron supplements
• Iron supplements have 2 forms, oral and parenteral. Oral iron is most commonly used
• Use of iron supplements helps in improving the iron status of the mother during pregnancy and during the postpartum period, even in women who enter pregnancy with reasonable iron stores
Iron Supplements
• Oral Iron (200 – 300 mg of elemental iron) with folic acid (500 microgram) prescribed in divided dose
• Type of oral supplement available :- Ferrous fumarate- Ferrous gluconate (If the above is not tolerated)- Ferrous glycine sulphate- Ferrous sulphate (dry)- Iron polysaccharide• Why Ferrous fumarate ?- Least expensive and best absorbed form of iron- Newer drugs ? Not proven yet
Oral Iron Supplements
• Anorexia
• Diarrhea
• Epigastric Discomfort (Combination with Vit C supplements)
• Nausea, Vomiting
• Constipation and Dark colored stool
• Temporary staining of teeth
*Oral Iron therapy must be continued for at least 12 months after the anemia has been corrected in order to replenish the depleted iron stores
Side Effects
• Start with one tablet daily first, then increase gradually until three times daily dosing
• Avoid use of high-dose Vit C supplements
• Taking with meals (But can also reduced iron absorption) – One hour before meal
• Administer at bed time
Methods of reducing side effects
• Daily oral iron and folic acid supplementation is recommended as part of the antenatal care to reduce the risk of low birth weight, maternal anaemia and iron deficiency (strong recommendation)
WHO Recommendation
• a 30 mg of elemental iron equals 150 mg of ferrous sulfate heptahydrate, 90 mg of ferrous fumarate or 250 mg of ferrous gluconate.
Suggested scheme Supplement composition Iron: 30–60 mg of elemental
ironFolic acid: 400 μg (0.4 mg)
Frequency One supplement daily
Duration Throughout pregnancy. Iron and folic acid supplementation should begin as early as possible
Target group All pregnant adolescents and adult women
Settings All settings
• An agent that increase the hemoglobin level and the number of erythrocytes in the blood
• Drug to stimulate RBC formation
• Primarily used in treatment of anemia
• Example –
- Iron (Oral, Parenteral)
- Folic Acid
- Vit B12
What is ‘hematinic’
According to period of gestation :
Less than 30 Weeks – Oral iron with folic acid
30 – 36 weeks – Parenteral Iron Therapy
Greater than 36 weeks – Blood Transfusion
Management of IDA in pregnancy
Advice on how to take iron tablet:
take several times a day on an empty stomach.
best to be taken at;
-bedtime
-or about an hour before a meal and at the same time drink juice that's rich in vitamin C, such as a glass of orange juice for optimum absorption of iron.
• Increased in reticulocytes- Increased 2 – 16%, by 4 – 6 days (earliest), pekas at 9 –
12 days.• Increased in hemoglobin levels (Rising at rate of 2 g/dl
after 3 weeks)• Total Plasma Iron will gradually increase and TIBC will
return to normal in about a month• Blood ferritin levels return to normal in about 4 – 6
months• Epithelial Changes (eg. Tongue and nails) revert to
normal
Increased in Hb in oral therapy
*Given over 6 – 8 hours under constant observation
Parenteral forms of IronIron preparation Route Elemental Iron Content
Iron Dextran(Imferon)
IM or IV 1ml = 50 mg FerricHydroxide +
Dextran
Iron sorbitolcitrate complex (Jectofer)
IV 1ml = 50mg Ferric Iron, sorbitol and
citric acid
Iron sucrose IV 1ml = 2mg Iron-ferrichydroxide in
sucrose
• Intolerance to oral form of iron• When iron deficiency is not correctable with oral
treatment• Non-compliance on part of the patient (Repeatly
fails to heed instructions/incapable of following them)
• Patient suffering from Inflammatory Bowel Disease (Aggravated by oral iron therapy)
• Patient is unable to absorb iron orally• Patients near term (32 – 36 weeks of pregnancy)
Indication of use of parenteral iron therapy
• IM - Pain and staining of the skin at the site of injection + Development of fever, chills, myalgia, athralgia, injection abscess
• IV - Serious side effect like anaphylaxis reactions (0.7%)
• Both – Systemic reactions
Immediate : Hypotension, headache, malaise
Delayed : Lymphadenopathy, myalgia, athralgia
Side Effects
• There is not enough time to achieve a reasonable Hb level before delivery. (For example, patient presents with severe anemia beyond 36 weeks)
• There is acute blood loss or associated infections
• Anemia is refractory to iron therapy
Indication for blood transfusion