Introduction to Thrombophilia

Question 1

What is thrombophilia? How is it recognised?

Answer 1

An increased tendency to thrombosis

Recurrent thrombosis, thrombosis at young age, Family Hx of thrombosis, Thrombosis whilst anticoagulated

Question 2

What are the factors that increase VTE risk?

Answer 2

Can be genetic, acquired or circumstantial

Virchows triad

Question 3

What is the importance in genetic factors in causing thrombosis?

Answer 3

Factor V Leiden - resistance to activated protein C

Increased thrombotic risk as there is less “past” partial inactivation of FVa

Question 4

Which mutation can increase risk of thrombosis?

Answer 4

Prothrombin gene polymorphism - PTG20210A, increases risk of thrombosis
heterozygotes show increase plasma prothrombin whilst homozygotes die in utero

Question 5

What is the molecular basis of FVleiden?

Answer 5

First cleavage partially inactivates FV, second completely inactivates
In the variant the cleavage site 506 is lost due to SNP
no initial cleaving therefore second cleavage can’t arise