Thrombin Generation in Myocardial Infarction and Hypercholesterolemia: Effects of Aspirin

Abstract

Over the last few years methods have been developed to assess appearance of thrombin during blood clotting in a clinical setting. This can be achieved either by measurement of the specific thrombin markers or by analysis of the thrombin generation kinetics. Thrombin markers rise following coronary occlusion and, surprisingly, their plasma levels become further increased during and after thrombolytic treatment with streptokinase or tissue-plasminogen activator. In myocardial infarction enhanced thrombin generation extends over the weeks, well beyond the acute phase of the disease. It indicates increased risk to a patient and might call for more anticoagulation or angioplasty. The benefit of aspirin as conjunctive treatment for thrombolysis has been clearly demonstrated. The well-founded concept is that aspirin exerts its anti-thrombotic action through inhibition of platelet cyclooxygenase. Recent evidence indicates that antithrombotic effects of aspirin might be explained, partly at least, by its inhibition of thrombin formation. Indeed, in both healthy subjects and survivors of myocardial infarction, aspirin, either at a single dose of 500 mg or at a dose of 300 mg per day administered over two weeks, effectively inhibits thrombinogenesis. Such response to aspirin is blunted in hypercholesterolemia. Subjects with high serum cholesterol levels might profit less than others from the anti-thrombotic action of aspirin.