The Pathogenetic Role of Apoptosis in Hypercoagulable States

Hypercoagulable states are common disorders with high risk of thrombosis associated with cardiovascular and malignant diseases. The pathogenesis of hypercoagulability is multifactorial. The basic physiological mechanism is the imbalance between anticoagulant activities and procoagulant activities in hemostatic system. In this review, we discuss the correlation between apoptosis and thrombogenesis in hypercoagulable states. Some cell-associated cofactors in coagulation system, including phosphatidylserine, tissue factor, thrombomodulin and cancer procoagulant, are regulated during apoptosis of various cell types. Vascular endothelial cells may act as one of the most important aspects affecting the balance of anticoagulant and procoagulant activities. When endothelial cells are activated or induced to undergo apoptosis by a number of physiological factors, such as inflammatory cytokines and bacterial lipopolysaccharide, the procoagulant activities of endothelial cells are enhanced. Other cell types such as apoptotic vascular smooth muscle cells, monocytes and macrophages may also contribute to the pathogenesis in atherosclerosis. Apoptotic tumor cells, which express high level of procoagulant activities, may act as a direct trigger for coagulation activation.