Coagulation and thrombosis in cardiovascular disease: plausible contributions of infectious agents.

An occlusive thrombus in the coronary arteries is the critical pathological event that immediately precedes most cases of myocardial infarction. Often the thrombus originates with a bleed from a fissured atheroma. Atheroma formation, therefore, creates risk of thrombosis; asymptomatic episodes of thrombosis and healing contribute to the pathogenesis of atherosclerosis and the development of atherosclerotic plaques. Based largely on in vitro and animal model evidence, infectious agents and their products can activate the coagulation cascade enzymatically or by up-regulating tissue factor. By initiating a procoagulant response, infectious agents can indirectly trigger a prothrombotic response. Alternatively, some microbes can directly trigger platelet aggregation in vitro and in animal models, suggesting direct prothrombotic potential in human cardiovascular disease. Activation of coagulation and thrombosis characterizes the pathological response to infectious agents in human disseminated intravascular coagulation and infective endocarditis. Given the underlying biological plausibility, the cumulative lifetime burden of chronic pathogens may be expected to create risk of atherosclerosis and thrombosis, and, indirectly, signs of cardiovascular disease.