PERSISTENT GENERATION OF THROMBIN AFTER ACUTE MYOCARDIAL-INFARCTION

During the acute phase of myocardial infarction, the generation of thrombin is reflected in the sudden rise of fibrinopeptide A (FPA) and the thrombin-antithrombin III (TAT) complex in blood. We have systematically determined the FPA and TAT plasma concentrations over a period of 14 days after acute myocardial infarction in 100 patients. Mean levels of both thrombin markers were the highest on admission, remained elevated over the following few days, and then gradually declined after day 5. Still, by the end of the first week two thirds of the patients had distinctly elevated TAT and FPA levels, and by the end of the second week such an abnormality was present in half of them. Continuous intravenous heparin infusion at a dose of 20,000 units/day, administered for 1 week to patients who bad either received (n = 21) or not received (n = 17) streptokinase, led to a significant depression (p < 0.05) of thrombin markers over the first 48 hours, an effect that did not persist over the subsequent days of treatment. In patients not assigned to heparin treatment, those in heart failure had significantly (p < 0.05) higher mean TAT and FPA values on days 3, 5, and 7 compared with patients in whom heart failure was absent. Infarct extension, pulmonary embolism, and death were also associated with a rise in one or both thrombin markers, often preceding the onset of clinical symptoms. Thrombinogenesis was not accompanied by changes in mean plasma concentrations of prothrombin, antithrombin III, or alpha-2-macroglobulin. It is suggested that thrombin was continuously released to the plasma from coronary or extracoronary thrombi undergoing lysis and subsequent rebuilding. Thus, thrombin generation that extends beyond the acute phase of myocardial infarction indicates an increased risk to the patients and might call for more anticoagulation, angioplasty, or the use of new antithrombotic agents.