Abstract
Venous thromboembolism constitutes a major medical problem afflicting millions of
individuals worldwide each year. Its pathogenesis is multifactorial, involving both
environmental and genetic risk factors. The most common genetic risk factor known
to date is a mutation in the factor V (FV) gene (R506Q or FV Leiden), which impairs
the normal regulation of FV by activated protein C (APC). APC is an important regulator
of blood coagulation, cleaving and inactivating not only FV/FVa but also activated
factor VIII (FVIIIa). In FVa, APC cleaves several sites, Arg506 (R506) being one of
them. The R506Q mutation results in the APC resistance phenotype and a lifelong hypercoagulable
state. A prothrombin gene mutation is another relatively frequent thrombosis risk
factor, whereas deficiencies of the anticoagulant proteins antithrombin, protein C,
or protein S are less common. As a result of the high prevalence of FV and prothrombin
mutations in the general population, combinations of genetic defects are relatively
common. Such individuals have highly increased risk of thrombosis.
Keywords
APC resistance - FV Leiden - TFPI
