PRACTICE POINT
General practitioners (GPs) play an important role in identifying potential of haemoglobinopathies. They also play an important role in identifying couples who are at risk of having a child with a haemoglobinopathy.
should be offered to all couples who are planning pregnancy or in the first trimester of pregnancy.
To enable timely reproductive choices during early pregnancy, carrier screening should be offered to couples at the same time (ie both partners should be tested as early as possible).
What do I need to know?
The term ‘haemoglobinopathies’ covers a range of conditions with an pattern that affect haemoglobin, including α-thalassaemia and β-thalassaemia, sickle cell disease and other abnormal haemoglobins, such as haemoglobin E (HbE).
Individuals with thalassaemia produce insufficient haemoglobin, while those with sickle cell disease produce structurally abnormal haemoglobin. The clinical implications range from mild through to death in utero.
Collectively, haemoglobinopathies are the most common single gene disorders in humans, and around 7% of the world’s population are carriers. Haemoglobinopathies are becoming more prevalent in Australia given immigration from endemic regions.
While carriers are often asymptomatic, carrier status becomes clinically significant in women who are carriers and planning a pregnancy, where the biological male partner is also a carrier.1 Screening for haemoglobinopathies is not part of newborn screening programs in Australia.
Carrier screening should be discussed as part of pre-pregnancy and prenatal care with all individuals: Those at particular risk are listed below but these should not be relied upon to identify carriers of a haemoglobinopathy:
- Those with family history of anaemia or haemoglobinopathy
- Those from the following ethnic backgrounds (have increased carrier frequency)
- southern European
- African
- Middle Eastern
- Chinese
- Indian subcontinent
- central and south-east Asian
- Pacific Islander
- New Zealand Maori
- South American
- Caribbean
- some northern Western Australian and Northern Territory Aboriginal and Torres Strait Islander communities
- Those with a mean corpuscular volume (MCV) <80 fL or mean corpuscular haemoglobin (MCH) <27 pg.
Genetic testing
Order a haemoglobinopathy screen to include:
- full blood examination (FBE) for MCV and MCH
- ferritin to exclude iron deficiency
- haemoglobin electrophoresis
- DNA testing if indicated (Table 1).
There is an urgency to test the biological male partner concurrently when an at-risk woman who is a carrier is pregnant. DNA testing is required when α-thalassaemia cannot be excluded and the partner is a known carrier of two-gene deletion α-thalassaemia (Table 1).
Table 1. Interpretation of haemoglobinopathy carrier testing results
MCH (pg)/MCV (fL)
|
Ferritin
|
Haemoglobin electrophoresis
|
Interpretation
|
MCH <27 and/or
MCV <80
|
Normal
|
HbA2 increased
|
β-thalassaemia carrier
|
|
|
HbA2 normal
HbH present
|
α-thalassaemia carrier
|
|
|
HbA2 normal
HbH high
|
Possible HbH α-thalassaemia
|
|
|
HbA2 normal
HbE present
|
HbE carrier or homozygote
|
|
|
Normal
|
Possible α-thalassaemia carrier; DNA testing indicated
|
|
Low
|
Normal
|
Iron deficiency
|
|
|
|
Thalassaemia may co-exist (treat iron deficiency then retest)
|
|
|
|
If woman is pregnant, seek advice about further tests
|
MCH ≥27 and/or MCV ≥80
|
Normal
|
Normal
|
Thalassaemia unlikely but one-gene deletion α-thalassaemia not excluded; DNA testing indicated only if partner is carrier of 2-gene deletion α-thalassaemia
|
|
Normal
|
HbS present
|
Carrier for sickle cell disease
|
|
Low
|
Normal
|
Reduced iron stores or iron deficiency, thalassaemia unlikely but one-gene deletion α-thalassaemia not excluded. Treat iron deficiency then retest
|
HbA2, normal variant of haemoglobin with two α-globin and two β-globin chains; HbE, abnormal variant of haemoglobin, due to abnormal β-globin; HbH, abnormal variant of haemoglobin, due to excess β-globin chains relative to β-globin chains, a type of α-thalassaemia; HbS, abnormal variant of haemoglobin, due to abnormal β-globin; MCH, mean corpuscular haemoglobin; MCV, mean corpuscular volume
Adapted from Metcalfe SA, Barlow-Stewart K, Campbell J, Emery J. Genetics and blood – Haemoglobinopathies and clotting disorders. Aust Fam Physician 2007;36(10):812–19.
When should I refer?
Urgent referral should be made to genetics and/or haematology services when carrier couples are identified during pregnancy in order to allow for timely reproductive decisions, or when a pregnant woman is identified as a carrier and testing of the biological male partner has not been done.
Urgent referral should be made to haematology services if a pregnant woman is found to have abnormal variant of haemoglobin (HbH) α-thalassaemia.
Other considerations
Do not assume low MCV or MCH is due to iron deficiency alone, especially in at-risk individuals. If the patient is not pregnant, treat for the iron deficiency then retest. If MCV or MCH remain low, the individual is possibly a carrier of a haemoglobinopathy. If the patient is pregnant, DNA testing for α-thalassaemia is indicated.
A woman only needs to have haemoglobinopathy screening once – if MCV or MCH is low but was previously normal, it is most likely due to iron deficiency.
Further reading
- Tan YL, Kidson-Gerber G. Antenatal haemoglobinopathy screening in Australia. Med J Aust 2016;204(6):226–30.
- The Royal Australian and New Zealand College of Obstetricians and Gynaecologists. Genetic carrier screening. 2019. https://ranzcog.edu.au/statements-guidelines Accessed 1 March 2022.
- The Royal Australian College of General Practitioners Guidelines for preventive activities in general practice. 9th edn. Melbourne: RACGP, 2016. [Accessed 6 September 2022].
- Norita Hussein , Lidewij Henneman , Joe Kai, Nadeem Qureshi. Preconception risk assessment for thalassaemia, sickle cell disease, cystic fibrosis and Tay-Sachs disease. Cochrane Database Syst Rev. 2021 Oct 11;10:CD010849. doi: 10.1002/14651858.CD010849.pub4.
Resource for general practitioners