What is Thalassaemia
Green-top Guideline No. 66 March 2014
Thalassaemia major women are those who require more than seven transfusion episodes per year
and
thalassaemia intermedia women are those needing seven or fewer transfusion episodes per year
or those who are not transfused.
Haemoglobinopathies are one of the most common inherited disorders.
Thalassaemia major (homozygous β thalassaemia) results from the inheritance of a defective β
globin gene from each parent.
This results in a severe transfusion-dependent anaemia.
The heterozygous state, β thalassaemia trait (thalassaemia minor) causes mild to moderate
microcytic anaemia with no significant detrimental effect on overall health.
Thalassaemia intermedia is defined as a group of patients with β thalassaemia whose disease
severity varies.
At the severe end of the clinical spectrum of thalassaemia intermedia, patients are usually diagnosed
between the ages of two and six years and, although they survive without regular blood transfusions,
growth and development are impaired.
At the other end of the spectrum, there are patients who are completely asymptomatic until
adulthood, when they present with mild anaemia and splenomegaly often found by chance during
haematological examinations or family studies.
The cornerstones of modern treatment in β thalassaemia are blood transfusion and iron chelation
therapy.
Multiple transfusions cause iron overload resulting in hepatic, cardiac and endocrine dysfunction.
The anterior pituitary is very sensitive to iron overload and evidence of dysfunction is common.
Puberty is often delayed and incomplete, resulting in low bone mass.
Most of these women are subfertile due to hypogonadotrophic hypogonadism and
therefore require ovulation induction therapy with gonadotrophins to achieve a
pregnancy.
Cardiac failure is the primary cause of death in over 50% of cases.
Improved transfusion techniques and effective chelation protocols have improved the quality of life
and survival of individuals with thalassaemia.
1) What are the additional risks to the woman and baby?
cardiomyopathy in the mother due to iron overload and the increased risk of fetal growth
restriction (FGR) with around 9 months of little or no chelation, women with thalassaemia major may develop new endocrinopathies.
in particular, diabetes mellitus, hypothyroidism and hypoparathyroidism due to the
increasing iron burden.
2) What is the optimum preconceptual care for women with thalassaemia?
screening for end-organ damage and
optimisation of complications prior to embarking on any pregnancy.
There is no contraindication to the use of hormonal methods of contraception such as the
combined oral contraceptive pill, the progestogen-only pill, the Nexplanon implant and the Mirena, intrauterine system in women with thalassaemia
2) Are there any interventions which are beneficial at the preconceptual stage?
Aggressive chelation in the preconception stage can reduce and optimise body iron burden
and reduce end-organ damage.
There is evidence from clinical trials that optimising body iron reduces end-organ damage
and can reverse cardiac iron loading.
Due to lack of safety data, all chelation therapy should be regarded as potentially teratogenic
in the first trimester.
Desferrioxamine is the only chelation agent with a body of evidence for use in the second
and third trimester.
Women with diabetes should be referred to a diabetologist.
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.
Diabetes mellitus is common in adults with thalassaemia.
Diabetes is multifactorial, due to insulin resistance, iron-induced islet cell insufficiency, genetic factors and autoimmunity.
Similar to women with diabetes without thalassaemia, an HbA1c of less than 43 mmol/mol
is associated with a reduced risk of congenital abnormalities.
HbA1c is not a reliable marker of glycaemic control as this is diluted by transfused blood
and results in underestimation, so serum fructosamine is preferred for monitoring.
Thyroid function should be determined. The woman should be euthyroid pre pregnancy.
Hypothyroidism is frequently found in patients with thalassaemia.
Untreated hypothyroidism can result in maternal morbidity, as well as perinatal morbidity
and mortality
All women should be assessed by a cardiologist with expertise in thalassaemia and/or iron
overload prior to embarking on a pregnancy.
An echocardiogram and an electrocardiogram (ECG) should be performed as well as T2*
cardiac MRI
Women should be assessed for liver iron concentration using a FerriScan or liver T2*.
Ideally the liver iron should be < 7 mg/g (dry weight) (dw).
Liver and gall bladder (and spleen if present) ultrasound should be used to detect
cholelithiasis and evidence of liver cirrhosis due to iron overload or transfusion-related viral
hepatitis.
All women should be offered a bone density scan to document pre-existing osteoporosis.
Serum vitamin D concentrations should be optimised with supplements if necessary.
ABO and full blood group genotype and antibody titres should be measured.
Alloimmunity occurs in 16.5% of individuals with thalassaemia.
3) What medications should be reviewed preconceptually?
Iron chelators should be reviewed and deferasirox and deferiprone ideally discontinued 3
months before conception.
Desferrioxamine has a short half-life and is safe for infusion during ovulation induction
therapy.
Desferrioxamine should be avoided in the first trimester owing to lack of safety data.
It has been used safely after 20 weeks of gestation at low doses.
All bisphosphonates are contraindicated in pregnancy and should ideally be discontinued 3 months prior to conception.
4) What is the importance of genetic screening and what procedure(s) are involved for
women with thalassaemia?
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 so >>>that a homozygous or compound heterozygous pregnancy can be avoided.
Egg and sperm donors considering IVF should be screened for haemoglobinopathies.
4) What is the importance of immunisation and antibiotic prophylaxis in women who are at
risk of transfusion-related viral infections or have had a previous splenectomy?
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.
allergic to penicillin should be recommended erythromycin.
All women who have undergone a splenectomy should be vaccinated
for pneumococcus and
Haemophilus influenzae type b if this has not been done before.
If a woman has a positive hepatitis C test, RNA titres should be determined with referral to
a hepatologist.
The pneumococcal vaccine (such as PneumovaxII, Sanofi Pasteur MSD Limited,
Maidenhead, UK) should be given every 5 years.
women should be given Haemophilus influenzae type b and the conjugated
meningococcal C vaccine as a single dose if they have not received it as part of primary
vaccination.
5) What vitamin supplements should be recommended?
Folic acid (5 mg) is recommended preconceptually to all women to prevent neural tube defects.
should be commenced 3 months prior to conception.
6) How is specialist input delivered for women with thalassaemia?
Women with thalassaemia should be reviewed monthly until 28 weeks of gestation and fortnightly
thereafter.
The multidisciplinary team should provide routine as well as specialist antenatal care.
Women with both thalassaemia and diabetes should have monthly assessment of serum
fructosamine concentrations and review in the specialist diabetic pregnancy clinic.
All women with thalassaemia major should undergo specialist cardiac assessment at 28 weeks of
gestation and thereafter as appropriate.
Thyroid function should be monitored during pregnancy in hypothyroid patients.
7) What is the recommended schedule of ultrasound scanning during pregnancy?
Women should be offered an early scan at 7–9 weeks of gestation.
In addition to the routine first trimester scan (11–14 weeks of gestation) and a detailed anomaly scan
at 18–20+6 weeks of gestation, serial fetal biometry scans every 4 weeks from 24 weeks of gestation.
early scan is indicated to determine viability as well as the presence of a multiple pregnancy.
8) How should the transfusion regimen be managed during pregnancy in women with
thalassaemia major?
All women with thalassaemia major should be receiving blood transfusions on a regular basis
aiming for a pretransfusion haemoglobin of 10 g/dl.
9) How should the transfusion regimen be managed during pregnancy in women with
thalassaemia intermedia?
If there is worsening maternal anaemia or evidence of FGR, regular transfusions should be
considered.
If a woman with thalassaemia intermedia starts transfusion, haemoglobin targets are
managed as for thalassaemia major.
Women with thalassaemia intermedia who are asymptomatic with normal fetal growth and
low haemoglobin should have a formal plan outlined in the notes with regard to blood
transfusion in late pregnancy.
Generally, in nontransfused patients,
if the haemoglobin is above 80 g/l at 36 weeks of
gestation, transfusion can be avoided prior to delivery.
Postnatal transfusion can be provided as necessary.
If the haemoglobin is less than 80 g/l then aim for a top-up transfusion of 2 units at 37–38 weeks of
gestation.
10) What antenatal thromboprophylaxis is recommended?
undergone splenectomy or have a platelet count greater than
600 x 109 /l should commence or continue taking low-dose aspirin (75 mg/day).
splenectomy and have a platelet count above
600 x 109 /l should be offered low-molecular-weight heparin thromboprophylaxis as well as low-dose
aspirin (75 mg/day).
Women with thalassaemia who are not already using prophylactic low-molecular-weight heparin should be advised to use it during antenatal hospital admissions.
11) What is the optimum antenatal management of iron chelation therapy?
Iron chelation therapy is complex and should be tailored to the needs of the individual woman.
The chelation should be managed by a haematologist with experience in iron chelation therapy
particularly during pregnancy.
12) Management of women with myocardial iron
Women with myocardial iron loading should undergo regular cardiology review with careful
monitoring of ejection fraction during the pregnancy as signs of cardiac decompensation are the
primary indications for intervention with chelation therapy.
Those women at highest risk of cardiac decompensation should commence low-dose subcutaneous
desferrioxamine (20 mg/kg/day) on a minimum of 4–5 days a week under joint haematology and cardiology guidance from 20–24 weeks of gestation.
As the cardiac T2* value falls below 20 ms there is an increasing risk of cardiac decompensation.
Those women at highest risk are those where the value is below 10 ms.
Women with myocardial iron loading and T2* > 20 ms do not require desferrioxamine chelation
during pregnancy unless there is severe hepatic iron overload.
If the woman complains of palpitations then a detailed history, ECG
and 24 hour ECG monitor assessment are needed to confirm a pathological cause.
In either circumstance desferrioxamine infusions may be indicated if there are concerns.
13) Management of women with liver iron
Women with severe hepatic iron loading should be carefully reviewed and consideration
given to low dose desferrioxamine iron chelation from 20 weeks.
the therapeutic aim is to achieve a liver iron concentration below 15 mg/g dw to reduce the risk of
myocardial iron overload
14) What is the best intrapartum management for women with thalassaemia major or
intermedia?
Timing of delivery should be in line with national guidance.
Senior midwifery, obstetric, anaesthetic and haematology staff should be informed as soon as the
woman is admitted to the delivery suite.
In the presence of red cell antibodies, blood should be cross-matched for delivery since this may
delay the availability of blood.
Otherwise a group and save will suffice.
In women with thalassaemia major intravenous desferrioxamine 2 g over 24 hours should be
administered for the duration of labour.
Continuous intrapartum electronic fetal monitoring should be instituted.
Thalassaemia in itself is not an indication for caesarean section.
Active management of the third stage of labour is recommended to minimise blood loss
15) What should be the optimum care post delivery?
Women with thalassaemia should be considered at high risk for venous thromboembolism.
Breastfeeding is safe and should be encouraged.
There is a high risk of venous thromboembolism due to the presence of abnormal red cells in the
circulation. Women should receive low-molecular-weight heparin prophylaxis while in hospital.
In addition, low-molecular-weight heparin should be administered for 7 days post discharge following vaginal delivery or for 6 weeks following caesarean section
Women with thalassaemia major who plan to breastfeed should restart desferrioxamine as soon as
the initial 24-hour infusion of intravenous desferrioxamine finishes after delivery.
Desferrioxamine is secreted in breast milk but is not orally absorbed and therefore not harmful to the newborn.
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