Genotype of proband and thrombophilia screening

Abstract

In this issue of Blood, Bucciarelli et al1 report on the risk for venous thrombosis (VT) among family members of heterozygous and homozygous carriers of 2 common polymorphisms, F5 rs6025 and F2 rs1799963, commonly known as the factor V Leiden (FVL) and the prothrombin (FII) gene G20210A (PT20210A) polymorphisms, respectively. F5 rs6025 yields an arginine to glutamine shift at position 506 of the mature factor V molecule, an important cleavage site for its inactivation by activated protein C, leading to slower inactivation of factor V and prolonged activation of coagulation,2 whereas F2 rs1799963 occurs in a regulatory region of the prothrombin gene that results in higher levels of prothrombin in plasma.3 As they lead to increased clotting factor activity or level, both are labeled "gain-of-function" polymorphisms to differentiate them from the mutations or polymorphisms that occur in the coagulation inhibitor genes, such as the antithrombin, protein C, and protein S genes, resulting in reduced activity or deficiency or "loss-of- function". © 2013 by The American Society of Hematology.