Pathophysiology and Natural History Coronary Artery Disease

Platelets have been implicated in the pathogenesis of coronary artery disease, and a number of studies have examined platelet function and coagulation parameters in such patients. We have examined platelet coagulant activities, volumes, and aggregate ratios in 23 patients with chest pain, seven of whom had normal coronary angiograms (group I) and 16 of whom had angiographically proven coronary artery disease (group II). There were no significant differences in the mean values for platelet volume or platelet aggregate ratios between the two groups. The platelet coagulant activities concerned with initiation and the early stages of intrinsic coagulation were significantly increased in patients in group II as compared with those in group I. No significant differences were noted between the two groups with respect to prothrombin time, partial thromboplastin time, and plasma levels of fibrinogen and coagulation factors V and VIII. However, the mean activity in plasma of antithrombin III (but not the level of antithrombin III antigen) was significantly lower in patients of group II compared with group I. Overall, our observations provide evidence for an enhanced contribution of platelets to the intrinsic coagulation system in patients with coronary artery disease. The platelet coagulant hyperactivity noted in these patients may reflect a role of platelets in the pathogenesis of coronary artery disease or may be secondary to the underlying arterial disease. Circulation 69, No. 1, 15-21, 1984. PLATELETS have been implicated in the pathogenesis of coronary artery disease, and a number of studies have been carried out to examine various aspects of platelet function in this disorder. These have included the study of platelet responses such as adhesion, aggregation, and the formation of vasoactive prostaglandin derivatives, the quantitation of platelet aggregate ratio and plasma levels of platelet-specific proteins (,Bthromboglobulin and platelet factor 4), and the estimation of the survival of platelets in patients with coronary artery disease.IA Previous studies carried out in our laboratory and those of other investigators have shown that human platelets participate in intrinsic coagulation at several stages, including the initiation of intrinsic coagulation From the Thrombosis Research Center, and the Cardiology Section, Department of Medicine, Temple University Health Sciences Center, Philadelphia. Supported by grants from the Ciba-Geigy Corporation, Summit, NJ, from the Council for Tobacco Research Inc., and by grants HL 14217 and HL 25661 from the Department of Health and Human Services. Address for correspondence: A. Koneti Rao, M.D., Thrombosis Research Center, Temple University Health Sciences Center, 3400 North Broad St., Philadelphia, PA 19140. Received May 16, 1983; revision accepted Sept. 22, 1982. This work was presented at the 53rd Scientific Sessions of the American Heart Association, Miami, FL, 1980 and was previously published in abstract form in Circulation 62 (suppl III): 111-275, 1980. Vol. 69, No. 1, January 1984 by two alternative pathways,5'the activation of factor X,8 and the activation of prothrombin.9 Assays for platelet coagulant activities have been developed in our laboratory and applied to the study of a variety of patients with thrombotic disorders.'s'4 We have suggested that platelet coagulant activities during the initiation and early stages of intrinsic coagulation are important determinants of normal hemostasis and that they may also play a part in the development of thromboembolic disease.'5 However, this role of platelets has not received attention in studies of platelets in coronary artery disease. Extensive studies have been carried out in patients with coronary artery disease defining the changes in plasma coagulation factors and platelets, but the interaction of platelets and the coagulation system has not been adequately examined. To assess the possible role of platelets in the pathogenesis of coronary artery disease, we have examined platelet coagulant activities, platelet volume, and platelet aggregate ratio in 23 patients who were evaluated for chest pain by coronary angiography; in 16 of these there was angiographic evidence of coronary artery disease. In addition, we have studied plasma coagulation and levels of antithrombin III in these patients. Our studies provide evidence of an enhanced contribu15 by gest on July 6, 2017 http://ciajournals.org/ D ow nladed from