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
o Type 1 or 2
- Combined FV + FVIII deficiency
- Discrepant 1-stage / 2-stage assays
A pregnant woman tells you she has a family history of ‘haemophilia’. How would you proceed?
- Explore pedigree
o Who is the index case and are they still alive / contactable?
- Patient’s bleeding history (Score >7 significant in women)
o Check VIII, IX, XI, VWF & others based on ethnicity
o Genetic sequencing – only takes 2 weeks
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
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%
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
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)