Persistent generation of thrombin after acute myocardial infarction.

Abstract

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 had 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 a^-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.

Failure of Thrombin Generation Markers to Triage Patients Presenting with Chest Pain

“…, 11, 12, 13]. The ability to predict the occurrence of acute coronary syndromes by serial measurements of TG markers has also been proposed [14, 15], but never proven in a prospective trial.…”

Thrombolytic Therapy in Acute Myocardial Infarction

“…This increase is still detectable 6 hours after the beginning of therapy, as reported by others, 10 whereas the later measurements of TAT complexes are at the level of those in patients with AMI but without thrombolytic therapy. 13, 21 The effect of streptokinase is confirmed by measuring fibrinopeptide A as a marker of thrombin action. 11,22,23 Detection of marked activation of thrombin after streptokinase was reported to be associated with failure of thrombolysis or early reocclusion.…”

Concentration of Endogenous tPA Antigen in Coronary Artery Disease

“…[1][2][3][4][5][6][7][8]11,12 Due to this causal relationship between angina at rest and thrombosis, the present data suggest that intracoronary thrombus formation is a strong and independent determinant for tPA antigen concentration in patients with angiographic evidence of CAD. In fact, based on in vitro data demonstrating a reactive release of tPA from the vascular wall after increase in thrombin concentration, 38 activation of thrombin in patients with acute coronary syndromes 43,44 is a possible explanation for systemically elevated tPA antigen concentrations in this subgroup. However, increased thrombin concentrations might explain not only acutely elevated tPA antigen concentrations in patients with angina at rest but also chronically elevated tPA levels in patients with stable CAD compared with healthy control subjects, 27,30,31 since clinically undetected ("silent") thrombotic events have been shown to occur frequently in atherosclerotic arteries.…”