RELATIONSHIP BETWEEN BLEEDING EVENTS AND CHANGES IN PLASMA IN PATIENTS TREATED WITH RECOMBINANT TISSUE PLASMINOGEN ACTIVATOR AND STREPTOKINASE IN TIMI STUDY-PHASE I

In Thrombolysis in Myocardial Infarction (TIMI) trial (Phase I) patients were randomized to receive intravenously either 80 mg of predominantly double~chain (G11021) recombinanttissue plasminogen activator(rt-PA) over 3 hrsor 1.5 million units of streptokinase (SK) over 60 min. All patients received an intravenous heparin bolus (5000 units) prior to angiography and a continuous infusion (1000 units/hr) starting 3 hr later.Bleeding occurred in 33% (rt-PA) and 31% (SK)of patients; over 70% of episodes were at vascular puncture sites. We report here the relationship between bleeding events and changes in plasma fibrinogen (FBG), plasminogen (PMG),and fibrin(ogen) degradation products (FDP) at 5 hr after initiation of drug infusion.Shown are number of patients with hemorrhage, total number of patients,and correlation coefficients (r) for occurrence of bleeding versus the changes in plasm proteins in each group.

The data indicate a relationship between bleeding events and changes in plasma proteins,with higher frequency of bleeding in patients with greater changes. FDP levels in both groups show a correlation with bleeding unlikely due to chance alone. While the hemorrhage may be due to multiple factors such as vigorous anticoagulation, arterial punctures, and platelet inhibition, the above findings suggestthat the plasma changes contribute to the hemorrhagic events.