Pathogenesis of Arterial and Venous Thrombosis

Abstract

Three primary influences predispose to thrombus formation, the so-called Virchow’s triad: (1) endothelial injury, (2) stasis or turbulence of blood flow and (3) blood hypercoagulability. Thrombotic formation is regulated by the thrombogenicity of exposed subendothelial constituents, local hemorheology, systemic thrombogenicity and fibrinolytic activity. Arterial thrombus is generally developed at disrupted atherosclerotic plaques. Platelet adhesion and aggregation are recognized as initial steps in arterial thrombus formation under rapid flow conditions. Since tissue factor is expressed in atherosclerotic plaques, coagulation pathways are also activated at plaque disruption sites, where thrombi comprising a mixture of aggregated platelets and fibrin develop. On the other hand, plaque disruption does not always result in total thrombotic occlusion. Although the mechanisms of arterial thrombus propagation in vivo remain unclear, not only increased vascular wall thrombogenicity and blood flow alterations, but also inflammatory reactions and circulating microparticles are considered key modulators of these mechanisms. Most venous thrombi occur in the deep veins of the legs. Hypercoagulability and blood stasis have been recognized as important factors in the genesis of venous thrombosis. Since the 2 factors facilitate activation of the coagulation pathway, it is generally understood that venous thrombi are mainly composed of a large amount of fibrin and erythrocytes, with relatively few platelets, known as red thrombi. However, venous thrombi and pulmonary emboli contained significant amounts of platelets and von Willebrand factor, in addition to fibrin and erythrocytes. The findings suggest that not only coagulation pathways but platelets play a significant role in venous thrombus formation.