Presentation: Pregnancy at risk of haemophilia A

A woman attends her booking appointment with her community midwife at her local GP surgery. She is six weeks pregnant with her first baby and is a known carrier of haemophilia A.

• Prenatal testing can be considered if the father is diagnosed with haemophilia A or the mother is a carrier.
• Carrier testing should be discussed with women who have a family history of haemophilia A and a familial pathogenic variant has been identified.

• Collect a detailed family and personal history from the couple.
• Refer the woman to clinical genetics for review by a clinical geneticist or a genetic counsellor.
• If seen pre-conceptually, refer the woman to an adult haemostasis consultant based in a haemophilia comprehensive care centre for genetic counselling, consideration of preimplantation genetic testing and ongoing shared pregnancy care with the woman’s local maternity provider.
• Haemostasis consultants with expertise in bleeding conditions will review the NHS England National Genomic Test Directory eligibility criteria to determine which test is the most relevant.
  • For information about how to arrange testing in Wales, Scotland or Northern Ireland, see Genomic testing in the devolved nations.
• Testing options may include the below.
  • Carrier screening:
    • R244 Carrier testing where there is a known familial variant(s). This is carrier screening for women who have a family history of haemophilia A with an identified genetic cause (pathogenic variant). Refer to local protocols, which may involve clinical genetics or haematology teams arranging testing.
  • Prenatal testing in a pregnancy in which one or both parents has a known familial disease-causing variant:
    • R251 Non-invasive prenatal diagnosis (NIPD) for fetal sexing. This can be performed after seven weeks of pregnancy. Contact your local Genomic Laboratory Hub (GLH) in advance to determine local processes.
      • Fetal sexing can inform management in pregnancy by determining risk of the pregnancy being affected. This is because haemophilia A is an X-linked condition, which means that:
        • affected fathers cannot pass the condition to their sons but their daughters will be carriers; and
        • for carrier mothers, each son is at 50% risk of being affected, and each daughter is at 50% risk of being a carrier.
      • Invasive testing is available for pregnancies in which the fetus is male and at risk of being affected:
        • R448 Prenatal testing with amniocentesis or chorionic villus sampling may be offered to test a male pregnancy for haemophilia A; and
        • R320 Invasive prenatal diagnosis requiring fetal sexing is available if NIPD to determine the fetal sex has not been possible.
  • If a patient presents prior to conception, preimplantation genetic testing may be available. Referral via clinical genetics is required.
• None of the tests outlined above use whole genome sequencing, so you should use your local GLH test order form and consent (record of discussion) form.
• Parental samples may be needed for interpretation of the proband’s result. Parental samples can be taken alongside that of the proband, and their DNA stored, or can be requested at a later date if needed.
• For fetal sexing NIPD, a blood sample in a Streck tube 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. Please refer to your local GLH for details of test request forms and where to send samples. For more information about different sample types, see Samples for genomic testing in rare disease.
• If you are discussing genomics concepts with your patients, you may find it helpful to use the visual communication aids for genomics conversations.
• 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

• NHS England: National Genomic Test Directory
• Royal College of Obstetricians & Gynaecologists: Management of inherited bleeding disorders in pregnancy (Green Top Guideline no. 71)
• West Midlands Regional Genomics Laboratory: NIPD for prenatal sex determination – R251 (PDF, 1 page)

For patients

• Haemophilia Society: Understanding haemophilia (PDF, 44 pages)
• NHS Health A to Z: Haemophilia