In vitro and In vivo Studies with Trasylol, an Anticoagulant and a Fibrinolytic Inhibitor

Abstract

Summary Trasylol is a competitive inhibitor of plasminogen activation by streptokinase and urokinase. The proteolytic activity of plasmin and trypsin is inhibited non‐competitively and the esterolytic activity of urokinase is inhibited in a mixed competitive and non‐competitive manner. These inhibitory effects are observed at high substrate concentrations. At low substrate concentrations, the inhibitory effects of Trasylol are relatively increascd. Trasylol is considerably more effective in vitro as an inhibitor of fibrinolytic activity than tranexamic acid and EACA: and in contrast to these amino acid inhibitors, Trasylol is more effective as an inhibitor of formed plasmin than of plasminogen activation.Trasylol possesses anticoagulant effects probably due to inhibition of prothrombin conversion and of intrinsic thromboplastin formation. Irt vivo in high dosage Trasylol imparts antifibrinolytic, anticoagulant and anti‐tryptic effects to plasma. It may accelerate platelet aggregation in vivo.In one patient with hypofibrinogenaemia, its administration was associated with a fall in the platelet count. In another patient there was evidence of a rise in fibrinogen Factor V, antihaeinophilic globulin (Factor VIII) and in the platelet count.An initial dosage of 100,000 units as a single injection or as an infusion given over 1 hour followed by maintenance dosage of 50,000 units/hr. seems appropriate in the treatment of pathological fibrinolysis. For the therapy of intravascular coagulation, higher dosage may be required, possibly 100,000 units/hr. This latter dosage would also be required in the treatment of systemic proteolysis due to trypsin.