RESULTS OF COAGULATION - FIBRINOLYSIS ANALYSES IN 386 PATIENTS WITH ACUTE MYOCARDIAL INFARCTION TREATED WITH RECOMBINANT TISSUE-TYPE PLASMINOGEN ACTIVATOR (rt-PA) (TAMI TRIAL)
Three hundred eighty-six patients with acute myocardial infarction received up to 150 mg rt-PA (single chain) IV either over 8 h (60mg over 1 h, 20 mg/h for 2 h,10 mg/h for 5 h)(173 pts) or over"5h(1 mg/kg over 1 h, remainder over 4 h) (213 pts),before randomization to early or late angioplasty. Blood was collected on a lyophilized mixture of citrate and the t-PA inhibitor D-Phe-Pro-Arg-CH2C1 (PPACK), to maximally prevent in vitro fibrinolytic activation and concomitant fibrinogen degradation. The plasma rt-PA level increased to 2.4±2.0 /μg/ml(mean +SD)and 1.7 ±1.3 /μg/ml after 3h and to 1.0 ±1.8 and 1.0 ±0.9 /μg/ml at the end of the infusion.Fibrinogen levels (coagulation rate assay) fell to 5 ± 28 and 52 ± 27% at 3 h and to53 ± 28 and 47 μ 26% at the endof infusion.Fibrinogen degradation productsincreased to 32 /μg/ml (median, with 10 and 90 percentile values of 2 and 512 /μg/ml) after 3h and to3 2 /μg/1 (median, with 10 and 90 percentile values of 2and 512 ug/ml) at the end of infusion. The fibrinogen decreased to below 1 g/1 in 23% of patients and b e low 0-5 g/1 in 11% after 3 h infusion with corresponding values of 33% and 12%at the end of infusion.Thus, at the infusion rates required for rapid coronary artery reperfusion in man, rt-PA remains relatively fibrin-specific. The cause of the extensive fibrinogen depletion occurring in some patients remains to be further investigated.