Presentation: Patient diagnosed with haemoglobinopathy disease or carrier status during pregnancy

A woman attends clinic concerned because results of a blood test completed at her recent antenatal booking appointment have shown that she is a carrier of an atypical haemoglobin. This was previously unknown to her.

• Partner testing should be offered when the mother is a carrier of sickle cell or thalassemia, has one of the conditions, or has an inconclusive result.
  • Testing may be haematological – that is, a blood film review and/or genomic testing.
  • Assessing for sickle cell carrier status usually does not require genomic testing because it is possible to diagnose using routine haematological investigations.
  • In thalassaemia conditions, it is possible to inherit one of a large range of genetic variants. Parental blood should be sent for molecular confirmation of carrier status.
  • If a woman has an inconclusive result, further maternal testing may be required depending on the variant suspected.
• If both parents are carriers of a significant haemoglobin variant or are affected by sickle cell disease or thalassaemia, or if the father’s status cannot be obtained, the woman should be referred to an appropriate fetal medicine service to discuss testing options.

• Collect a detailed family and personal history from the couple.
• If seen pre-conceptually, refer the case to clinical genetics for pre-conception counselling and to discuss options.
• If seen with an ongoing pregnancy, follow local protocols and refer the case to your local screening team.
• The relevant team will refer to the NHS England National Genomic Test Directory eligibility criteria to determine which tests are available to your patient. The directory itself provides a list of all available tests.
  • For those working within NHS Wales, please consult the All Wales Medical Genomics Service website for information on how to arrange testing.
• Genomic testing options depend on the specific condition but may include:
  • Carrier screening for patient and partner:
    • R361 Haemoglobinopathy trait or carrier testing: For parents whose carrier status has been confirmed by a haematology screening (excluding sickle cell disease) and whose carried genetic variants need to be confirmed in order to inform genomic testing on the invasive test sample.
    • R362 Carrier testing for sickle cell disease: For parents whose carrier status has been confirmed by a haematology screening and whose carried genetic variants need to be confirmed in order to inform genomic testing on the invasive test sample.
    • Both the above tests require an EDTA sample. Please refer to your local Genomic Laboratory Hub (GLH) for details of test request forms and where to send samples.
    • Public Health England has published comprehensive guidelines on when to refer for molecular testing (see the sickle cell and thalassaemia antenatal laboratory handbook). This process is designed to identify couples at risk of severe haemoglobinopathies so that prenatal diagnosis can be performed in a timely fashion.
  • Prenatal testing in a pregnancy with a known familial disease-causing variant:
    • Invasive testing.
  • If the patient presents pre-conceptually, pre-implantation genomic testing for monogenic disorders may be available. Referral via clinical genetics is required.
• For invasive tests, an amniocentesis or chorionic villus sample, or fetal blood sample (in an EDTA tube) is required, as well as a sample from the mother to test for maternal cell contamination. For many of the tests, parental samples are also needed or are helpful. Please refer to your local GLH for details of test request forms and where to send samples. It is important to contact the GLH in advance of any testing.
• A record of discussion form, or another appropriate local consent form, is required for testing.
• Information about patient eligibility and test indications was 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

• NICE: Antenatal care guidelines
• NHS England: National Genomic Test Directory
• NHS England: Referral of antenatal samples for molecular analysis
• NHS England: Sickle cell and thalassaemia screening programme: Standards

For patients

• NHS: Screening for sickle cell and thalassaemia
• NHS England: Sickle cell and thalassaemia information
• NHS England: Sickle cell and thalassaemia screening: Information for fathers
• Sickle Cell Society: Sickle cell disease information and support
• UK Thalassaemia Society: Thalassaemia information and support