Thalassaemia

Question 1

Define beta thalassaemia intermedia

Answer 1

Defined by RCOG as 7 or less transfusions per year or no transfusions per year

Question 2

Define beta thalassaemia major

Answer 2

Homozygous beta thalassaemia trait - RCOG defines as more than 7 transfusions per year

Question 3

Define haemoglobin H

Answer 3

3 alpha globin chains affected - haemoglobin consists of tetrameric beta and gamma chains - results in anaemia and splenomegaly

Question 4

Define haemoglobin Barts

Answer 4

4 alpha globin chains affected - tetrameric gamma chains - incompatible to life - leads to fetal hydrops or early neonatal death (hb has a high affinity for oxygen)

Question 5

Consequence of 1 defective alpha globin chain

Answer 5

Silent trait

Question 6

Consequence of 2 defective alpha globin chains

Answer 6

alpha thalassaemia trait - mild anaemia

Question 7

Consequence of beta thalassaemia major on pregnancy

Answer 7

Mild to moderate anaemia - folic acid 5mg recommended, iron replacement can be given if deficient, if symptomatic of anaemia, transfusion can be considered, risk of transmission to fetus

Question 8

Pre-conception considerations of beta thal major and intermedia

Answer 8

Pituitary - hypogonadotrophic hypogonadism (ovulation induction with gonadotrophins, consider preimplantation genetic diagnosis)
Thyroid - low thyroid
Liver - iron, cirrhosis, gall stones
Pancreas - diabetes (test with fructosamine)
Heart - iron, cardiomegaly, heart failure, dysrhythmia
Blood - risk of VTE, infection risk (hep B/C), alloimmunisation
Infection - hepB/C, if splenectomy (risk of encapsulated infections)
Bone - osteoporosis

Question 9

How is iron tissue deposition assessed in beta thal major and intermedia pre-conception

Answer 9

T2* cardiac MRI >20ms = low risk, <10ms high risk
T2* liver MRI or ferriscan - aim for 7mg/g dry weight pre conception, if >15mg/g high risk of cardiac iron - offer chelation 20-24 weeks

Question 10

How is iron chelation managed pre-conception?

Answer 10

Aggressively.
Oral regimes should be stopped 3 month prior to conception (teratogenic)
IV desferrioxamine (short half life) can be used during ovulation induction

Question 11

How often should beta thal intermedia and major be seen in pregnancy?

Answer 11

early scan 7-9 weeks, dating and anomaly scan, 4 weekly scans from 24 weeks
Monthly until 28 weeks then every 2 weeks in clinic
joint haem/mat med MDT involvement
Cardiac review at 28/40

Question 12

What is the implication for beta thal major/intermedia on developing fetus?

Answer 12

Alloantibodies secondary to multiple transfusions = risk of fetal and neonatal haemolysis
Fetal growth restriction

Question 13

What are the implications for beta thal major/intermedia on pregnant woman?

Answer 13

Co-morbidities - hypothyroid, diabetes
Cardiac decompensation and dysrhythmia in labour
Iron deposition as no longer using chelating agents
VTE risk

Question 14

How should VTE risk be managed in beta thal major and intermedia?

Answer 14

Splenectomy or plt >600 = aspirin
Splenectomy AND plt >600 = aspirin and LMWH
Antenatal admission = LMWH
Postpartum LMWH

Question 15

How should patients with beta thal major and intermedia be assessed for diabetes?

Answer 15

Hba1c is inaccurate - serum fructosamine should be used

Aim for <300 pre conception

Question 16

What is the intrapartum management of beta thal major and intermedia?

Answer 16

If alloantibodies - crossmatch 2 units
Mode and timing is obstetric decision
Beta thal major - desforoxamine, 2g 24 hour infusion in labour 
Continuous CTG monitoring
Active management of 3rd stage

Question 17

What is the postpartum management of beta thal major and intermedia?

Answer 17

Encourage to breast feed
Can restart oral chelating agents
LMWH prophylaxis

Question 18

What is the indication for transfusion in pregnancy for beta thal major and intermedia?

Answer 18

FGR or worsening maternal anaemia (e.g. <100)

If <80 at 37-38 weeks - transfuse, if >80 and not previously transfused at 36 weeks - don’t transfuse

Question 19

What is the indication for iron chelation in pregnancy for beta thal major and intermedia?

Answer 19

iron chelation is done with low dose desferioxamine at 20-24 weeks for patients with either evidence of high risk cardiac decompensation T2*MRI <10ms, hepatic iron overload >15mg/g dry weight

Question 20

What is the frequency of alloimmunisation in beta thal major patients?

Answer 20

16.5%

Question 21

What is the frequency of alloimmnisation in sickle cell disease patients?

Answer 21

18-36%