FIBRINOGEN BREAKDOWN, LONG-LASTING SYSTEMIC FIBRINOLYSIS, AND PROCOAGULANT ACTIVATION DURING ALTEPLASE DOUBLE-BOLUS REGIMEN IN ACUTE MYOCARDIAL-INFARCTION

Recent clinical studies comparing accelerated versus bolus administrat ion of alteplase tissue plasminogen activator (t-PA) suggest similar t hrombolytic efficacy, but reveal higher bleeding complications among o lder patients during the double-bolus regimen. The objective of the pr esent study was to characterize the hemostatic profile of t-PA adminis tered as double-bolus doses of 50 mg, at intervals of 30 minutes. Amon g 50 patients with acute myocardial infarction treated by double-bolus t-PA thrombolysis, coagulation and fibrinolysis parameters, as well a s t-PA levels, were monitored. Monitored t-PA levels peaked at 5 and 3 5 minutes and were detectable within the therapeutic range even after 90 minutes. Marked systemic fibrinolytic activation was indicated by 7 5% depletion of both plasminogen and of fibrin degradation and fibrino gen degradation products. Plasminogen-activator inhibitor activity was completely suppressed. Pronounced procoagulant activation was reflect ed by a 3.4-fold increase of both factor XIIa and prothrombin fragment 1+2, and by a threefold increase of thrombin-antithrombin complex. In dependent of t-PA weight dosage, fibrinolytic activation was more pron ounced among older patients (greater than or equal to 63 years). We co nclude that t-PA after bolus administration has a long half-life. Doub le-bolus regimen leads to a long-lasting systemic fibrinolytic state, which is even more remarkable among older patients-a fact that may exp lain the higher bleeding complications reported for this age group. (C ) 1998 by Excerpta Medica, Inc.