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Thrombin, Inflammation, and Cardiovascular Disease: Clinical CVD

A major form of CVD is myocardial infarction (MI); in the early 1970s, it became evident, through the work of DeWood and colleagues” and others, that the proximal event in MI is commonly an occlusive blood clot in a coronary artery. The term vulnerable plaque has been used to describe a form of atherosclerosis characterized by rapid, focal lipid accumulation, with the development of a large pool of subendothelial fat covered by a thin, mechanically fragile cap. There is often little intrusion into the lumen of the vessel, with considerable remodeling into the vessel wall to accommodate the lipid build-up. As the cap ruptures, the cells and soluble factors of the coagulant system are exposed to this large pool of presumably procoagulant lipid, along with many subendo-thelial components deep into the arterial wall, which results in platelet activation and aggregation, thrombin generation, and the development of a large often occlusive thrombus. If not cleared quickly, significant myocardial damage ensues. more
Arterial clots are often so-called “white clots” (ie, platelet-rich), suggesting less of a role for fibrin formation; however, the direct role of thrombin as the ultimate clotting enzyme in this setting is obvious. As others in this supplement will illustrate in detail, thrombin is not only responsible for the cleavage of fibrinogen resulting in fibrin formation, but is also the most powerful platelet agonist, and is believed to play a critical role in the growth of platelet aggregates.
CVD encompasses more than MI. Other coronary syndromes, such as sudden coronary death, may not have a thrombotic component to the same degree or extent. For example, autopsy studies have revealed that sudden coronary death is associated with coronary thrombosis in > 70% of the cases in younger adults (when the precipitating cause is most frequently incident MI), but that this prevalence decreases to less than a third in older adults.