Resistance to activated protein C as pathogenic factor of venous thromboembolism

Venous thromboembolism is a serious health problem and a significant cause of morbidity and mortality. It is associated with certain situations such as surgery, trauma, immobilization, obesity, the use of oral contraceptives, pregnancy and puerperium. In addition, genetic factors have been found to be important in the pathogenesis of venous thrombosis and pulmonary embolism. Until recently, the main genetic defects known to be associated with thromboembolism were antithrombin III, protein C and protein S deficiency accounting together for about 10% of the cases. In 1993 Dahlbäck et al. reported a familial thrombophilia due to a previously unrecognized mechanism characterized by an increased resistance to anticoagulant action of activated protein C (APC). APC-resistance is highly prevalent in general population (2-7%) and in its heterozygous form leads to a life-long hypercoagulable state and 5-10 fold increased risk of thrombosis. It is a major basis for venous thromboembolism and is found in 17 to 64% of patients with inherited thrombophilia.