ACTIVATED PROTEIN-C RESISTANCE DUE TO A COMMON FACTOR-V GENE MUTATIONIS A MAJOR RISK FACTOR FOR VENOUS THROMBOSIS

Inherited resistance to activated protein C (APC) was recently discove red to be a cause of familial thrombophilia and is now known to be the most common genetic risk factor for venous thrombosis. It is caused b y a single point mutation in the gene for factor V, which predicts sub stitution of arginine (R) at position 506 with a glutamine (Q). Accord ingly, the activated form of mutated factor V (FVa:Q(506)) is more slo wly degraded by activated protein C than normal FVa (FVa:R(506)) is, r esulting in hypercoagulability and a lifelong 5- to 10-fold increased risk of venous thrombosis. Previously known inherited hypercoagulable states, i.e. deficiencies of the anticoagulant proteins antithrombin I II, protein S, and protein C, are found in fewer than 10-15% of thromb osis patients in western countries, whereas inherited APC resistance i s present in 20-60% of such patients. The FV mutation is common in pop ulations of Caucasian origin, with prevalences ranging from 1-15%, whe reas it is not found in certain other ethnic groups such as Japanese a nd Chinese. The high prevalence of APC resistance, in combination with the availability of simple laboratory tests, will have a profound inf luence on the development of therapeutic and prophylactic regimens for thrombosis and will, it is hoped, result in a decreased incidence of thromboembolic events.