Dynamics of coronary thrombolysis and reocclusion

The dynamics of coronary thrombosis and reocclusion may seem straightforward, but in actuality they are complex and incompletely understood. The pathobiology of coronary thrombosis begins with the development of the atherosclerotic plaque. The initial step in the process, endothelial cell dysfunction, alters vascular thromboresistance. Plaque erosion or overt disruption is followed by platelet adherence, aggregation, and thrombin generation that stimulates the conversion of soluble fibrinogen to fibrin. Thrombolytic therapy, although able to dissolve a high proportion of occlusive thrombi, creates a procoagulant environment by generating plasmin which, in turn, activates platelets and generates thrombin, increasing the likelihood of vessel reocclusion. Thrombin is therefore considered an important target for research, and several thrombin inhibitors have been developed. Antiplatelet agents such as aspirin are currently employed to prevent reocclusion following thrombolytic therapy; however, several new and more potent platelet antagonists are being investigated with considerable enthusiasm.