FIBRINOGENOLYSIS AND THROMBIN GENERATION AFTER REDUCED DOSE BOLUS OR CONVENTIONAL RT-PA FOR PULMONARY-EMBOLISM

The aim of this study was to compare the effects on fibrinogenolysis a nd thrombin generation of two recombinant tissue-type plasminogen acti vator (rt-PA) regimens in patients with pulmonary embolism entering a randomised, controlled study with a 1:2 allocation ratio to rt-PA, 100 mg over 2 h (Group A) or rt-PA, 0.6 mg/kg, maximum dose 50 mg, over 1 5 min (Group B). In both groups the heparin infusion was stopped 2-4 h before starting thrombolytic treatment and resumed accordingly to the activated partial thromboplastin time (aPTT) or thrombin clotting tim e (TcT). Seventeen patients in Group A and 30 patients in Group B were evaluated before starting thrombolytic treatment and 2, 6 and 24 h af ter its end for the following parameters: aPTT; TcT, fibrinogen, fibri nogen degradation products (FDP), plasmin-alpha(2) antiplasmin (PAP) a nd thrombin-antithrombin III (TAT) complexes. The two groups had simil ar coagulation parameters at baseline. Two h after starting rt-PA, the aPTT was more prolonged in Group A than in Group B patients (P = 0.01 ). Patients in Group B showed less reduction in plasma fibrinogen leve ls at all study times after rt-PA treatment (P = 0.008). The increase in plasma FDP (P = 0.037) and PAP (P = 0.001) levels was lower at 2 an d 6 h samples in Group B compared with Group A. TcT was prolonged (P = 0.003) and TAT increased (P = 0.001) during treatment without differe nces between the two groups. AUC(0-24) of fibrinogen, FDP and PAP leve ls confirmed the statistically significant differences (P = 0.04) betw een the two groups over the entire 24 h period of the study. Three pat ients in Group A (17.6%) and three (10.0%) in Group B suffered major o r other important bleeding. Our results indicate that the administrati on of weight-adjusted reduced-dose rt-PA bolus produces less impairmen t of blood coagulation than the FDA approved regimen.