Effect of reteplase on hemostasis variables: analysis of fibrin specifity, relation to bleeding complications and coronary patency

Abstract 

The first aim of the present study was to characterize the systemic and fibrin-specific lytic effect of reteplase in the treatment of patients with acute myocardial infarction. The second aim was to investigate the relation of hemostasis variables to risk of bleeding complications and to coronary patency. The present study is a hemostatic substudy of the German Recombinant Activator Study. Forty two patients have been treated with 10 MU of reteplase (Group A) and 100 patients with 15 MU of reteplase (Group B), given as a single bolus. Blood samples for assessment of fibrinogen, plasminogen, alpha-2-antiplasmin, fibrinogen degradation products (FDP) and D-dimers were obtained before and at 2, 4, 8, and 24 h after thrombolytic therapy. The median fibrinogen concentration was decreased from 279 to 169 mg/dl in Group A and from 254 to 92 mg/dl in Group B four hours after administration of reteplase. The decrease in fibrinogen was significantly more pronounced in Group B (P=0.0004). The median plasminogen concentration was decreased to 53% in Group A and to 33% in Group B two hours after administration of reteplase (P=0.0001). Alpha-2-antiplasmin was reduced to 27% and 17,5%, respectively (P=0.0007). D-Dimer levels were increased to 5.2 μg/ml in Group A and 11,6 μg/ml in Group B (P=0.02) and FDP levels to 3.0 μg/ml in Group A and 12,6 μg/ml in Group B (P=0.04). Patients with bleeding complications revealed significant lower nadir levels of fibrinogen than patients without bleeding complications (54 mg/dl versus 125.5 mg/dl, P=0.02). There was no significant difference in any hemostatic parameter between patients with patent and nonpatent infarct related arteries. Conclusions: Reteplase causes a moderate systemic lytic effect comparable with other relative fibrin specific thrombolytic agents. An increase in the dose from 10 to 15 MU is associated with a marked increase in both fibrin specific and systemic lytic effect. Patients with bleeding complications reveal significant lower nadir levels of fibrinogen than patients without bleeding complications. Determination of any hemostatic parameter seems to be no useful method to predict efficacy of thrombolysis in terms of coronary patency in the individual patient.

Keywords:  Reteplase, Hemostatic variables, Thrombolytic therapy, Coronary patency, Bleeding complications