Beta thalassaemia

Question 1

Outline postpartum mx

Answer 1

Remember (for general PP mx):

• VTE
• BF
• Baby
• F/u

VTE prophylaxis (high risk for VTE)

Encourage breastfeeding (desferrioxamine secreted in breastmilk, though not orally absorbed, therefore safe for the infant)

If possibility neonate may have inherited the condition, discuss with Paeds/genetics re: testing

Haematology follow-up

Question 2

Outline antenatal mx

Answer 2

MDT - diabetologist/obstetric physician if DM/GDM, cardiologist, haematologist, obstetrician (MFM), midwife experienced in high risk care, anaesthetist, +/- Paeds

Ideally will have undergone pre-pregnancy counselling, partner testing, +/- PIGD or gamete donation. If not, discuss prenatal testing (CVS/amniocentesis)

Discontinue iron chelators at least 3 months prior to pregnancy (may need to be restarted in pregnany depending on iron load).

Folic acid 5mg, iodine

VTE - Tendency to thrombosis due to presence of abnormal red cell fragments (esp. if previous splenectomy). Hence, women who have undergone splenectomy or have a platelet count >600 should commence low-dose aspirin. If they have both, offer LMWH thromboprophylaxis + low dose aspirin.

Question 3

Outline investigations you would perform pre-pregnancy or early pregnancy in a woman with beta thalassaemia

Answer 3

Investigation

Justification

FBC – Hb and MCV

Establish baseline

If Hb < 100 will require RBC transfusions

If platelets > 600 need low dose aspirin (and if previous splenectomy add LMWH)

Blood group and antibody screen

Will have received multiple blood transfusions – risk of developing RBC antibodies

• May delay provision of RBC
• May have implications for fetal anaemia/haemolytic disease of the newborn i.e. anti-D, anti-Kell, anti-c

B12/folate levels

Another preventable cause of anaemia

At risk of low B12/folate as increased erythropoiesis increases demands

Should receive 5 mg folic acid daily throughout pregnancy

Ferritin and iron studies

Transfusion-dependent patients develop iron overload because no physiologic process to remove excess iron from multiple transfusions

Review chelation agents - aim to stop prior to pregnancy

ECHO, ECG and cardiac MRI

Assess for cardiac complications of iron overload i.e iron overload cardiomyopathy and associated arrhythmias

LFTs, coagulation profile, hepatitis screen, hepatic USS

Iron overload can lead to hepatic damage or liver failure

At risk for hepatitis after multiple RBC transfusions

Thyroid function tests

Iron overload can cause hypothyroidism (anterior pituitary dysfunction)

Diabetes screening - fructosamine

Iron overload can cause diabetes

HbA1c limited usefulness as diluted out from multiple transfusions

Paternal thalassaemia status and genotype

To determine risk to fetus of being beta-thalassaemia homozygous (will inherit one copy of defective gene from homozygous mother)

If paternal genotype is heterozygous for beta-thalassaemia, consider CVS or amniocentesis for fetal genetic analysis, as 50% chance of fetus having beta-thalassaemia major

If paternal genotype homozygous, then 100% chance of fetal beta-thalassaemia major

Question 4

Pathophysiology of beta thalassaemia

Answer 4

Result of deficient or absent synthesis of beta globin chains - regulated by one gene on each chromosome 11.

• One-gene defect = beta thalassaemia trait (minor) - asymptomatic, microcytosis, mild anaemia
• If synthesis from both genes severely reduced or absent - beta thalassaemia major - not symptomatic at birth (have HbF), symptoms develop at ~ 6 months of age

If synthesis of beta chains less severely reduced = beta thalassaemia intermedia - sx are less severe, do not require lifelong transfusions to survive past age 20 yrs

Question 5

How is beta thalassaemia diagnosed?

Answer 5

Most patients with trait are found incidentally - CBC showing mild microcytic anaemia. DDx for microcytic anaemia = TAILS (thalassaemia, anaemia of chronic disease, IDA, lead poisoning, sideroblastic anaemia)

Ix for diagnosis:

• Ferritin
• Blood film (for sideroblastic anaemia)
• Hb-electrophoresis - usually has reduced or absent HbA, elevated levels of HbA2, and increased HbF
• Serum lead level

Question 6

Outline pre-pregnancy counselling for a woman with beta thalassaemia

Answer 6

Usual proforma:

• general advice (diet, GWG, exercise, healthy eating etc)
• Hx: MSPF, meds (stop chelators - though may need aggressive chelation pre-pregnancy if iron load is high), start folic acid 5mg, iodine 150 mcg), review transfusion requirements
• Ex: BMI, BP, urinalysis
• Ix: FBC, ferritin, cardiac MRI (iron loading), echo, liver USS/MRI (iron loading), LFTs, TSH (pituitary failure secondary to iron load), HbA1c (DM due to pancreatic damage)
• Genetics: genetic counselling, partner carrier testing, +/- PIGD/gamete donation/prenatal diagnosis
• MDT: haematologist, MFM/high risk obstetrician

Counsel:

• Risk of condition on the pregnancy: early pregnancy loss (offer USS at 7 - 9 weeks), IUGR (if severe anaemia), affected fetus, increased risk GDM (hence screen), hypothyroidism (screen)
• Risk of the pregnancy on the condition: may need iron chelation during pregnancy (avoid in first trimester as all chelation agents teratogenic) with desferrioxamine if iron load is high, need intrapartum ECG + IV desferrioxamine due to increased free radicals due to unbound iron (cardiotoxic), increased risk of VTE (discussed in another card)