Question 1

Give a differential diagnosis for a FVIII:C of 0.15 iu/ml

  • Mild haemophilia A

  • Haemophilia A on factor concentrate prophylaxis

  • Von Willebrand Disease

    • Type 1 or 2

  • Combined FV + FVIII deficiency

  • Discrepant 1-stage / 2-stage assays


Question 2a

A pregnant woman tells you she has a family history of ‘haemophilia’. How would you proceed?

  • Explore pedigree

    • Who is the index case and are they still alive / contactable?

  • Patient’s bleeding history (Score >7 significant in women)

  • Bloods

    • Check VIII, IX, XI, VWF & others based on ethnicity

    • Genetic sequencing – only takes 2 weeks


Question 2b

You find nothing from the above, what possibilities remain?

  • Rare coag disorder

  • Platelet function disorder

  • 3-5% of Haemophilia A families do not have a detectable mutation


Question 3a

In an asymptomatic woman, whose father has severe haemophila A and mother is normal, what is the risk that her daughter is a carrier of severe haemophilia A?

  • Superficially the daughter will be an obligate carrier, having taken X from father

  • But the quoted non-paternity rate in the UK is 1%


Question 3b

The daughter is a carrier (FVIII 0.68 iu/ml). She goes on to have two twin girls of her own. One twin has a FVIII of 0.69 iu/ml. What would you predict the levels to be in the other twin?

  • Could be the same

  • Or could be very low due to mirror image lyonisation between the twins


Question 4

In which situations can you be sure someone is an obligate carrier?

  • If they are a daughter of an affected mother

  • If they are the mother of two affected children

  • (not if they are the daughter of an affected father for reasons of non-paternity)