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
A pregnant woman tells you she has a family history of ‘haemophilia’. How would you proceed?
Who is the index case and are they still alive / contactable?
Patient’s bleeding history (Score >7 significant in women)
Check VIII, IX, XI, VWF & others based on ethnicity
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)