Perspectives Physiological Anticoagulation Resistance to Activated Protein

Venous thromboembolism is a serious, potentially lethal health problem affecting 1 per 1,000 people annually (1-3). Major surgery, fractures, complicated pregnancy, the use of oral con-traceptives, and immobilization increase the risk of thrombosis. In addition, thrombosis is often familial, suggesting that genetic risk factors are involved (3-6). Until recently, the major ge-netic defects known to predispose for thrombosis were defi-ciencies of antithrombin III, protein C, and protein S. Together these did not account for more than 5-10 % of the cases (3-5, 7). In the last year, hereditary activated protein C (APC)' resistance, has been identified as a basis for a majority of cases of familial thrombosis (8-13). In contrast to other genetic de-fects associated with thrombosis, APC resistance is highly prev-alent in the general population (8, 10). It afflicts affected indi-viduals with a life-long increased risk of thrombosis. APC resis