Mechanisms of Thrombus Formation in the Onset of Cardiovascular Events

Abstract

Occlusive thrombus formation on disrupted atherosclerotic plaque is the major cause of cardiovascular events. Accumulating evidence indicates that inflammation plays a key role in plaque instability and thrombus formation. The thrombotic response to plaque disruption (rupture or erosion) is regulated by the thrombogenicity of exposed plaque constituents, local hemorheology, systemic thrombogenicity and fibrinolytic activity. Platelet adhesion and aggregation are recognized as initial steps in arterial thrombus formation under rapid flow conditions. However, tissue factor is expressed in atherosclerotic plaques, coagulation pathways are also rapidly activated at plaque disruption sites. Autopsy studies of acute myocardial infarction have revealed that thrombi on disrupted plaques are principally composed of aggregated platelets and a large amount of fibrin with many inflammatory cells. Thrombi from ruptured plaques are significantly richer in fibrin than those on eroded plaques, and more tissue factor is expressed in ruptured than eroded plaques.On the other hand, plaque disruption does not always result in total thrombotic occlusion. Although the detail mechanisms of arterial thrombus propagation in vivo remain unclear, recent studies have demonstrated that increased vascular wall thrombogenicity together with a substantial blood flow alteration is crucial for occlusive thrombus formation leading to the onset of cardiovascular events.