Hereditary thrombophilia and venous thromboembolism

Abstract

The hereditary thrombophilias are a group of inherited conditions that predispose to thrombosis. Heritable deficiencies of the endogenous anticoagulants protein C, protein S, and antithrombin have been recognized for some years, but their prevalence, even among patients with familial thrombosis, is low. The recent discoveries of two relatively common thrombophilias, resistance to activated protein C associated with an abnormal factor V gene (factor V Leiden), and prothrombin gene variant 20210A, have substantially increased the likelihood of identifying a heritable predisposing factor in patients with thromboembolism. Modestly elevated levels of plasma homocysteine, which are in part genetically determined, have also recently been associated with an increased risk for venous thromboembolism. A predisposition to thrombosis can now be identified in a substantial minority of patients with venous thromboembolism, and in the majority of patients with familial thrombosis, and there is accumulating evidence that multiple coexisting defects are present in persons with the most marked tendency to thrombosis. The most common causes of hereditary thrombophilia are reviewed with an emphasis on resistance to activated protein C, prothrombin variant 20210A, and hyperhomocystinemia, and the current status of laboratory testing for thrombophilia is discussed.