Presentation: Patient with abnormal antenatal haemoglobinopathy screening results

A pregnant 30-year-old woman and her husband request an appointment to discuss her “blood problem”. Her shared record shows that she has seen the midwife and had blood taken for haemoglobinopathy screening. The results reveal a mild microcytic anaemia and an interim lab report suggests that she is a carrier of thalassaemia. The patient’s family are from Thailand and her husband is of Greek Cypriot origin. The midwife has met with the couple to discuss testing the baby’s father, but he is reluctant.

• Haemoglobinopathy carriers may be clinically unaffected but have a persistent mild microcytic anaemia with normal ferritin. In these patients, oral iron supplementation may not be necessary or beneficial.
• The NHS screening programme is administered differently depending on whether the local NHS trust has a high prevalence of haemoglobinopathies (greater than or equal to 2% of booking bloods screening positive) or a low prevalence (less than 1% of booking bloods screening positive). The NHS and Public Health England screening programme handbook includes a list of high- and low-prevalence trusts.
  • In high-prevalence trusts, haemoglobin variant and thalassaemia testing is offered to all pregnant women regardless of family origin.
  • In low-prevalence Trusts, an examination of the red blood cell indices for indications of thalassaemia is performed for all consenting women, and a family origin questionnaire (FOQ) is completed. Maternal testing for haemoglobin variants is offered if the FOQ suggests that either parent has high-risk ancestry.
• Flags for an underlying genetic diagnosis include:
  • Mediterranean, Arabic, Asian or African ancestry (although haemoglobinopathies can occur in all ethnic groups);
  • family history of haemoglobinopathy; and
  • persistent microcytic anaemia with normal ferritin and iron studies.

• Further testing and referral for genomic counselling and prenatal diagnosis are usually arranged by the midwife and the maternity services team; however, this may differ in different geographical centres.
• Diagnosis of newly identified carrier status needs explaining, with reassurance that in most cases there will be no impact on the patient’s health.
• If the mother is a significant carrier (that is, she is a carrier of a gene for a major haemoglobin disorder rather than a benign variant, as defined in the screening programme guidelines) or is diagnosed with a haemoglobin disorder (whether benign or clinically significant), the father should be offered testing to allow determination of the risk of them having an affected baby.
• DNA testing of both the mother and the father may be necessary, as individuals may carry more than one genetic variant (multiple variants can combine to modify symptoms and disease).
• Haematology referral is recommended for those with a new diagnosis of a benign haemoglobin disorder (such as haemoglobin C disease), but local referral criteria may vary. Most of these women continue with routine antenatal care. Testing of the father is recommended as co-inheritance of two or more different haemoglobinopathy genes can lead to disease.
• In rare cases, antenatal screening may lead to the first diagnosis of a significant maternal haemoglobin disorder (such as sickle cell disease or beta thalassaemia). These women require urgent referral to haematology and obstetrics services.
• For information about how to arrange testing in Wales, Scotland or Northern Ireland, see our dedicated Knowledge Hub resource.
• Information about patient eligibility and test indications were correct at the time of writing. When requesting a test, please refer to the National Genomic Test Directory to confirm the right test for your patient.

For clinicians

• Antenatal Results and Choices
• NHS sickle cell and thalassaemia screening programme: Family origin questionnaire (PDF, two pages)
• Public Health England: NHS sickle cell and thalassaemia screening programme handbook (PDF, 89 pages)

References:

• Ryan K, Bain BJ, Worthington D and others. ‘Significant haemoglobinopathies: Guidelines for screening and diagnosis’ British Society of Haematology 2010: volume 149, issue 1, pages 35–49. DOI: 10.1111/j.1365-2141.2009.08054.x

For patients

• Antenatal Results and Choices
• NHS pregnancy: Screening for sickle cell and thalassaemia
• Sickle Cell Society
• UK Thalassaemia Society