USEFULNESS OF FIBRINOGENOLYTIC AND PROCOAGULANT MARKERS DURING THROMBOLYTIC THERAPY IN PREDICTING CLINICAL OUTCOMES IN ACUTE MYOCARDIAL-INFARCTION

Thrombin activity is increased in the setting of acute myocardial infa rction (AMI) and has been shown to increase further after the administ ration of thrombolytic therapy for acute infarction. This increase in thrombin activity may play an important role in the 15% to 25% rate of failure to achieve initial reperfusion and in the 5% to 15% rate of e arly reocclusion after initially successful thrombolysis. To investiga te potential mechanisms of thrombin formation in vivo, to understand b etter the balance of coagulation and fibrinolysis during treatment wit h recombinant tissue-type plasminogen activator (rt-PA), and to invest igate the role of hemostatic markers as predictors of clinical events, we measured 3 markers of procoagulant activity: fibrinopeptide A (FPA ), thrombin-antithrombin III complexes (TAT), and prothrombin fragment 1.2 (F1.2), and a marker of fibrinogenolytic activity (B beta 1-42) i n patients enrolled in the Thrombolysis in Myocardial Infarction (TIMI )-5 study. This trial was a randomized, dose-ranging, pilot trial of h irudin versus heparin as adjunctive antithrombotic therapy with rt-PA administered to patients with AMI. Correlation of markers at 1 hour wi th clinical outcomes revealed that increased FPA and TAT levels were a ssociated with increased mortality and TIMI grades 0, 1, or 2 flow at 90 minutes; increased F1.2 levels were associated with TIMI grade 0 or 1 flow at 90 minutes; and increased levels of all 3 procoagulant mark ers were associated with hemorrhagic events. Late (12 to 24 hours) inc reases in F1.2, TAT, and B beta 1-42 may be predictive of recurrent is chemia. These results suggest that selected markers of procoagulant an d fibrinogenolytic activity may be useful in predicting clinical outco mes in patients treated with thrombolytic therapy for AMI.