EDITORIALS

Platelet Aggregation and Thrombotic Vascular Disease THROMBOSIS, frequently the final event in coronary or cerebral arterial occlusion, is a result of the interplay of abnormalities of the vessel wall, hemodynamic forces, plasma coagulant proteins, and platelets. Platelets are thought to initiate a series of intricate reactions by adhering to the injured arterial lining, aggregating irreversibly to form a platelet plug, and releasing vasoactive metabolites and hydrolytic enzymes that might in turn alter both the function and structure of the vessel. Heightened platelet function thus might not only participate in the formation of thrombi but also may play a role in the development or progression of some forms of atherosclerosis. The paper in this issue by Sagel and associates (p. 733) reports on the finding that 39 prediabetic, latent, or frankly diabetic subjects had increased platelet aggregation to the aggregating agents ADP, epinephrine, and collagen. The more advanced the diabetic involvement, the greater was the degree of platelet response. The enhanced second wave of aggregation was reversed with acetylsalicylic acid, tolbutamide, or glucose ingestion. The authors, in reviewing their own data and those of earlier workers, postulate that this abnormal sensitivity may predispose to thrombotic occlusion of small vessels. Other types of thrombotic vascular disease associated with enhanced platelet aggregation have also been documented. In the acute stages but not convalescent periods of both myocardial infarction and stroke, an eightfold decrease in ADP concentration needed for microscopic platelet aggregation was demonstrated in 12 patients (1) compared with age-matched controls. Other investigators have found an increased extent of platelet aggregation in response to a suboptimal dose of A D P in patients with previous myocardial infarction 2 or more months after the acute episode ( 2 ) . The end point used for ADP response or patient selection might account for the differences in these two studies. Recently, similar findings have been documented in patients with angina pectoris but without recent myocardial infarction, diabetes, or lipid abnormalities ( 3 ) . The mean concentration for a full (biphasic) ADP-induced platelet aggregation in patients with angina was less than half that of matched normal controls. Administration of propranolol at a dose that increased the exercise performance of these subjects returned the sensitivity to normal levels. The relation, if any, between the diminished aggregability of the platelets and the increased exercise performance after propranolol is not known. Patients with familial hyperbetaliproprotenemia

(type

I l a ) , a condition known to predispose to premature and excessive morbidity and mortality from atherosclerosis and its thrombotic complication, show increased platelet sensitivity ( 4 ) . Compared with normal subjects, platelets from these subjects gave a full response to 1/25 the mean concentration of epinephrine and 1/3 the concentration of ADP or collagen. Furthermore, nucleotide and serotonin release were increased in type-II patients. These findings are probably not related to the presence of young, larger, and therefore hyperactive platelets because platelet turnover is normal in type-II patients. This lack of correlation is emphasized by the observation that type-IV hyperlipoprotenemic patients with shortened platelet survival have normal platelet sensitivity. Clofibrate appears in epidemiologic studies to have a beneficial effect on morbidity in type-II patients without effect on lipid levels. This interesting observation may be explained by the recent report (5) that clofibrate in vitro or in vivo can diminish platelet sensitivity in type-II and normal subjects. Thus, four groups of patients, each with accelerated thrombotic vascular disease, appear to have associated platelet hypersensitivity. Although at least three classes of drugs can reverse this in-vitro abnormality, correlation with in-vivo platelet behavior and clinical response to therapy must be established before guidelines for pharmacologic intervention can be recommended. (ROBERT W. COLMAN,

M.D., F.A.C.P., Coagulation Unit, Hematology-Oncology Section, Department of Medicine, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania)

References 1. SANO T, BOXER MGJ, BOXER LA, et al: Platelet sensitivity to

aggregation in normal and diseased groups. A method for assessment of platelet aggregability. Thromb Diath Haemorrh 25:524531, 1971 2. GOLDENFARB PB, CATHEY MH, ZUCKER S, et al: Changes in the

hemostatis mechanism after myocardial infarction. Circulation 43:538-546, 1971 3. FRISHMAN WH, WEKSLER B, CHRISTODOULOU JP, et al: Reversal

of abnormal platelet aggregability and change in exercise tolerance in patients with angina pectoris following oral propranolol. Circulation 50:887-896, 1974 4. CARVALHO ACA, COLMAN RW, LEES RS: Platelet function in

hyperlipoproteinemia. N Engl J Med 290:434-438, 1974 5. CARVALHO ACA, COLMAN RW, LEES RS: Clofibrate reversal of

platelet hypersensitivity in hyperbetalipoproteinemia. Circulation 50:570-574, 1974 Editorials

Downloaded from https://annals.org by Tulane University user on 01/12/2019

839

Editorial: Platelet aggregation and thrombotic vascular disease.

EDITORIALS Platelet Aggregation and Thrombotic Vascular Disease THROMBOSIS, frequently the final event in coronary or cerebral arterial occlusion, is...
232KB Sizes 0 Downloads 0 Views