Pathology and Pathophysiology of Atherothrombosis: Virchow's Triad Revisited

Abstract

In 1856, Rudolf Virchow published “Cellular pathology” based on macroscopic and microscopic observation of diseases, and described a triad of factors on thrombosis. The three components were vascular change, blood flow alteration, and abnormalities of blood constituents. Although Virchow originally referred to venous thrombosis, the theory can also be applied to arterial thrombosis, and it is considered that atherothrombus formation is regulated by the thrombogenicity of exposed plaque contents, local hemorheology, and blood factors. Thrombus formation on a disrupted atherosclerotic plaque is a critical event that leads to atherothrombosis. However, it does not always result in complete thrombotic occlusion with subsequent acute symptomatic events (Sato et al., 2009). Therefore, thrombus growth is also critical to the onset of clinical events. In spite of intensive investigation on the mechanisms of thrombus formation, little is known about the mechanisms involved in thrombogenesis or thrombus growth after plaque disruption, because thrombus is assessed with chemical or physical injury of “normal” arteries in most animal models of thrombosis.