Activated protein C resistance, factor V Leiden, and venous thromboembolism

Factor V Leiden mutation is the most common inherited defect of coagulation currently known, with a prevalence between 3% and 6% in Caucasian populations. The result of a single adenine-for-guanine point mutation in the gene coding for coagulation factor V, factor V Leiden leads to a hypercoagulable state in part by rendering a key binding site on coagulation factor Va partially resistant to the anticoagulant effects of activated protein C. Clinically, this state is referred to as activated protein C resistance. Individuals affected by factor V Leiden appear to be at significantly increased risks of first and recurrent venous thrombosis, particularly those events not associated with cancer, surgery, or trauma. Moreover, risks of venous thrombosis among carriers of factor V Leiden dramatically increase in the presence of other acquired coagulation defects including hyperhomocysteinemia and oral contraceptive use. Screening programs for factor V Leiden must carefully consider the prevalence of mutation in a given population, the absolute as well as relative risks imparted by the mutation, and the benefit-to-risk ratio associated with any therapeutic intervention based upon a positive test finding. Ongoing clinical studies such as the Prevention of Recurrent Venous Thromboembolism (PREVENT) trial will help to determine whether individuals who carry factor V Leiden and have had a first venous thrombosis should be considered for chronic, low-dose anticoagulation therapy.