pregnancy with beta thalassemia

Pregnancy with beta thalassemia

Dr. Mamuni SultanaRegistrar

Department of Obs. & GynaeKhulna Medical College Hospital

Particulars of the patient

• Name : Mrs. Lipica• Age : 25 years• Religion : Shanaton• Occupation: Housewife• Socioeconomic condition: Middle class• Address : Pabla, Doulotpur, Khulna• Husband Name : Mahafuz Mollah• Date of admission : 10/06/15• Date of examination : 10/06/15

Chief complaints

1. Amenorrhoea for 38 weeks. 2.Less fetal movement for 1 day 3. Known case of beta thalassemia major for 9 years.

History of present illness According to the statement of the pt. she was amenorric for 38 wks. Her pregnancy was confirmed by urine test. She was in regular antenatal check up and was duly immunized . Her pregnancy was uneventful up to 16 wks. Then she developed generalised weakness and anorexia. For this reason she took 3 units of blood transfusion after getting admission in Obstertric department

During her subsequent antenatal check up she received total 10 units of blood after getting admission total 3 times in KMCH. She was non diabetic & normotensive.

History of past illnessShe had ill health, generalized weakness and

pallor since her childhood and took 3 units of blood at her 15 years of age and diagnosed as a case of beta thalassemia major in 2006. Science then she took blood transfusion several time including during and after her previous pregnancies.

Family HistoryNo history of consanguinous of marriage. Neither her family members nor her husband was investigated for thalassemia or other hemoglobinopathies.

Obs. History Married for: 12 Years Para: 2(VD)+0 Gravida: 3rd Age of last child: 5 yearsNone of them was investigated for thalassemia or other hemoglobinopathies.

Menstrual history MP/MC: Regular MF: average L.M.P: 17/09/14 E.D.D: 24/06/15

General examination•Appearance- Anxious, ill looking•Body built- Below average •Anaemia- Mild•Jaundice- Absent•Cyanosis- Absent•Oedema- Absent•Dehydration- Absent•Temperature- Normal( 98 F)•Pulse-68/min•B.P-120/70 mmHg•Height- 4 feet 8 inch

• Thyroid gland- not enlarged• Lymph node- not palpable• Breasts- shows normal pregnancy changes.• Cardiovascular system- reveals no abnormality• Other systems- Seems to be normal.

Per abdominal examination FH- 36 wksF.M- presentPresentation- CephalicLie- LongitudinalLiquor- Seems to be less than adequateF.H.R- 140 beats/min

Per vaginal examination• Cervix- Soft, posterior• Os- Parous• Station- High up• Membrane- Intact• Pelvis – Seems to be adequate

Clinical diagnosis

3rd Gravida 38 weeks pregnancy with thalassemia major with IUGR with oligohydramnios

InvestigationsIx Date Value

Hb% 03.02.15 4.9 gm/dl

11.03.15 7 gm/dl

13.04.15 6.9 gm/dl

PBF 03.02.15 Hemolytic anemia

S. ferritin level 09.02.15 260 ngm/ml

USG of pregnancy profile

08.02.1511.03.15

HepatospleeenomegalyIUGR with Oligohydramnios

Obstetric managementLUCS with BLTL done on 11.06.15 due to3rd Gravida 38 weeks pregnancy with thalassemia major with IUGR with oligohydramnios . Baby note: Sex: MaleWeight: 2 kgLiquor: LessApgar score: 18510

No visible congenital anomaly

Beta Thalassaemia

Epidemiology More than 70000 babies are born with

thalassaemia worldwide each year.100 million individuals asymptomatic thalassaemia carriers.

Previously, the community affected was principally from

• Cyprus • Mediterranean.

currently the Asian communities of

• India• Pakistan• Bangladesh account for 79% of thalassaemia births with only

7% occurring in the Cypriot population

The basic defect Reduced globin chain synthesis with the resultant

red cells having inadequate haemoglobin content.

Pathophysiology Extravascular haemolysis due to the release into the peripheral

circulation of damaged red blood cells and erythroid precursors because of a high degree of ineffective erythropoiesis.

β thalassaemia major homozygous thalassaemia results from the inheritance of a defective β globin gene from each

parent a severe transfusion-dependent anaemia. β thalassaemia trait (thalassaemia minor) heterozygous state, mild to moderate microcytic anaemia no significant detrimental effect on overall health.Thalassaemia intermedia group of patients with β thalassaemia whose disease severity varies.

Modern treatment• Splenectomy is no longer the mainstay of treatment• The cornerstones of modern treatment in β

thalassaemia are

Iron chelation therapy

stem cell transplantation The only treatment protocol that can cure

thalassemia is stem cell transplant. Transplant of blood and marrow stem cell can replace abnormal stem cells with healthy donor cells.

Experimental In-Utero Gene Therapy Researchers are striving to find new treatments

For instance gene therapy- to insert a healthy hemoglobin gene into stem cells in bone marrow. This would allow people to create their own normal red blood cells and Hb

Multi organ damage

Multiple transfusions cause iron overload resulting in dysfunction

• Hepatic

• Cardiac

Cardiac failure primary cause of death in over 50% of cases

• Endocrine

anterior pituitary • Puberty is often delayed and incomplete • Low bone mass• Subfertile due to hypogonadotrophic

hypogonadism require ovulation induction therapy with gonadotrophins to achieve a pregnancy

Risks to the mother and babyMother • Cardiomyopathy • Diabetes mellitus • Hypothyroidism • Hypoparathyroidism

Fetal • Fetal growth restriction (FGR)

• Intrauterine death

Beta Thalassaemia in Pregnancy

Preconceptual care

Genetic screening Screening for end-organ damage Optimisation of complications

Genetic screening If the partner is a carrier of a haemoglobinopathy

that may adversely interact with the woman’s genotype then genetic counselling should be offered.

In vitro fertilisation/intracytoplasmic sperm injection (IVF/ICSI) with a pre-implantation genetic diagnosis (PGD) should be considered in the presence of haemoglobinopathies in both partners

pre-implantation genetic diagnosis (PGD)

chorionic villus sampling

amniocentesis

Iron chelation therapy

prolonged period of iron chelation therapy may be required to control iron overload prior to both

• induction of ovulation• PregnancyAggressive chelation in the preconception stage

reduce and optimise body iron burden reduce end-organ damage

Pancreas• Diabetes is common in women with thalassaemia.

• Good glycaemic control is essential prepregnancy.• Women with established diabetes mellitus should

ideally have serum fructosamine concentrations < 300 nmol/l for at least 3 months prior to conception. This is equivalent to an HbA1c of 43 mmol/mol.

Thyroid

Thyroid function should be determined. The woman should be euthyroid prepregnancyHypothyroidism is frequently found Untreated hypothyroidism can result in maternal

morbidity perinatal morbidity and mortality.

Heart

• All women should be assessed by a cardiologist with expertise in thalassaemia and/or iron overload prior to embarking on a pregnancy.

Performed• Echocardiogram • ECG • T2* cardiac MRI.

Liver

Women should be assessed for liver iron concentration using a

• FerriScan® • Liver T2*.

Ideally the liver iron should be < 7 mg/g (dry weight) (dw).

Liver and gall bladder (and spleen if present) ultrasound to detect

• cholelithiasis • liver cirrhosis

due to iron overload or transfusion-related • viral hepatitis.

Bone density scanAll women should be offered a bone density scan to

document pre-existing osteoporosis. Serum vitamin D concentrations should be optimised with supplements if necessary.

Red cell antibodies

ABO and full blood group genotype and antibody titres should be measured

Medications should be reviewed preconceptually

• Iron chelators deferasirox and deferiprone ideally

discontinued 3 months before conception.

All bisphosphonates contraindicated in pregnancy and should ideally be

discontinued 3 months prior to conception

Immunisation and antibiotic prophylaxis

• Hepatitis B vaccination is recommended in HBsAg negative women who are transfused or may be transfused

• Hepatitis C status should be determined.

• All women who have undergone a splenectomy should take penicillin prophylaxis or equivalent.

• All women who have undergone a splenectomy should be vaccinated for

pneumococcus Haemophilus influenzae type b if this has not been done before

Supplements recommended• Folic acid (5 mg) is recommended

preconceptually to all women to prevent neural tube defects.

Antenatal care• Specialist input delivered for women with thalassaemia monthly until 28 weeks of gestation fortnightly thereafter • Both thalassaemia and diabetes monthly assessment of serum fructosamine • Specialist cardiac assessment at 28 weeks of gestation thereafter as appropriate.• Thyroid function should be monitored

Recommended schedule of ultrasound scanning

Viability scan at 7–9 weeks of gestation.

Routine first-trimester scan (11–14 weeks of gestation)

Detailed anomaly scan at 20 weeks of gestation.

Serial fetal biometry scans (growth scans) every 4 weeks from 24 weeks of gestation.

BPD AC FL

BPD AC FL

Transfusion regimen

• All women with thalassaemia major should be receiving blood transfusions on a regular basis aiming for a pretransfusion haemoglobin of 100 g/l.

• Transfuse every 2–5 weeks, maintaining pre-transfusion Hb above 9–10.5 g/dl, but higher levels (11–12 g/dl) may be necessary for patients with heart complications.

• Keep post-transfusion Hb not higher than 14–15 g/dl.

Antenatal thromboprophylaxis recommended

• Thalassaemia with splenectomy or platelet count greater than 600 x 109/l

Low-dose aspirin (75 mg/day).• Thalassaemia with splenectomy and platelet

count greater than 600 x 109/l Low-molecular-weight heparin as well as Low-dose aspirin (75 mg/day).

Optimum antenatal management of iron chelation therapy

Teratogenic• Deferasirox • Deferiprone

Desferrioxamine • Short half-life • Safe for infusion during ovulation induction therapy.• Should be avoided in the first trimester owing to lack of

safety data• Used safely after 20 weeks of gestation at low dose

Myocardial ironHighest risk of cardiac decompensation Low-dose subcutaneous desferrioxamine (20

mg/kg/day) on a minimum of 4–5 days a week from 20–24 weeks of gestation

Liver ironLow dose desferrioxamine iron chelation from 20

weeks.(liver iron > 15 mg/g dw as measured by MRI)

Intrapartum care

• Intravenous desferrioxamine 2 g over 24 hours should be administered for the duration of labour.

• Continuous intrapartum electronic fetal monitoring

• Thalassaemia in itself is not an indication for caesarean section.

• Active management of the third stage of labour is recommended to minimise blood loss

Postpartum care

• High risk for venous thromboembolism.low-molecular-weight heparin should be administered for 7 days post discharge following vaginal delivery6 weeks following caesarean section

• Breastfeeding is safe and should be encouraged.