Fibrinolysis. V. The thrombolytic and anticoagulant activity of mold fibrinolysin (Aspergillin O) in vivo.

Abstract

Abstract Detailed studies were carried out on the fibrinolytic and clot-delaying activity of Aspergillin O in 70 dogs. There was no evidence of toxicity or antigenicity with an average dose of 10 mg. per kilogram of weight and with repeated administrations at various intervals of time. The effect of Aspergillin O in vivo lasted approximately one hour after the administration of the drug. There appeared fibrinolytic activity in whole blood and plasma without evidence of activation of profibrinolysin (plasminogen). There were also delayed formation and decreased yield of thrombin, moderate fibrinogenopenia, and some deficiency of clot accelerators. There was no significant acceleration of the clotting process with the dose employed. Venograms demonstrated the recanalization of venous vessels thrombosed for 24 to 48 hours, but Aspergillin O was unable to destroy thrombi older than 72 hours. The addition of heparin (0.2 mg. per Kiloweight) enhanced the anticoagulant and fibrinolytic activity of the drug. In dogs, Aspergillin O destroyed intravenous thrombi experimentally produced, while it delayed and interfered with the normal coagulation mechanism without hemostatic breakdown or acceleration of intravasoular clotting. Its complex mechanism of activity suggested the potential use of the drug in the management of thromboembolic disease in man.