Question1

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

 

Question 2a

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)

-       Bloods

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

o   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)