Prevention of fibrinogenolysis without impairment of thrombolysis: Combination of A Plasminogen Activator with a2-antiplasmin

The thrombolytic therapy is usually associated with bleeding risks due to a systemic fibrinogenolysis. We investigated whether it is possible to block fibrinogenolysis without impairing the lytic activity of fibrin-bound plasmin molecules. The present data show that at increased a2-antiplasmin levels as high as 6-fold the normal concentration fibrinolysis was not impaired, while the haemostatic parameters as aPTT, TT and the fibrinogen concentration remained normal. Essentially similar results were observed with all plasminogen activators (streptokinase, urokinase and a t-PA mutant) assayed. The use of a2-macroglobulin leads to identical observations. With aprotinin, however, a complete inhibition of the lysis was observed. The data presented here show that it is possible with the combined use of a plasminogen activator and a2-antiplasmin to reach at least in vitro a normal fibrinolysis without impairment of the haemostatic parameters.