Role of platelets and thrombosis in mechanisms of acute occlusion and restenosis after angioplasty

Abstract

The vascular disruption produced by angioplasty initiates platelet deposition through the processes of platelet adhesion and recruitment of circulating platelets to form an enlarging mural platelet thrombus. Thrombin produced by simultaneous activation of the coagulation cascade by subendothelial connective tissue structures enhances platelet deposition and stabilizes the forming thrombus with enmeshing fibrin. Platelet recruitment involves the expression of the glycoprotein II b III a a receptor for fibrinogen and other cytoadhesive proteins including fibronectin, thrombospondin and von Willebrand factor. Platelet deposition and thrombus formation caused by angioplasty appear to be important in the development of 2 complications: acute thrombotic occlusion and restenosis. Experimental mechanical vascular injury produces a predictable, although rather variable, amount of vascular narrowing due to transient smooth muscle cell proliferative initimal lesion formation. This intimal thickening by proliferating smooth muscle cells is in part mediated by platelet mitogens, particularly platelet-derived growth factor, which are released into the damaged vessel from platelets at the time of angioplasty. Platelet-derived growth factor may also be released from other associated vascular and blood cells in response to mechanical injury, e.g., endothelium, monocyte/macrophage and smooth muscle cells themselves. The actual mitogens, and their cells of origin, that mediate restenosis after therapeutic angioplasty remain to be established. Various oral antiplatelet agents have been shown to reduce arterial thrombotic occlusion in a number of controlled clinical trials, e.g., aspirin in transient ischemic attacks and unstable angina, aspirin and dipyridamole in saphenous vein coronary artery bypass and progression of peripheral vascular disease and dipyridamole in artificial heart valves. Acute arterial thrombosis may require more potent, immediate and transient intervention, e.g., monoclonal antibody to platelet receptor expression. Properly controlled trials using various antiplatelet regimens are indicated in angioplasty patients to evaluate their capacity to prevent restenosis.