Studies on the production of intravascular thrombi and their treatment with fibrinolysin.

IT HAS been shown in experimental animals that the human fibrinolytic enzyme (plasminogen activated with streptokinase) will dissolve fresh intravascular thrombi." Fibrinolytic agents are also undergoing an extensive clinical trial and the preliminary reports which have appeared*" have suggested that this type of therapy will be of value in the management of thrombo-embolic disorders. Variations in the response of patients to therapy have indicated that factors related to the clot, or to the patient's general condition, may alter the lysis of intravascular thrombi. The experiments to be reported were undertaken to investigate, under controlled conditions, some of the factors which might determine the response to fibrinolytic treatment. It is hoped that the information gained will be of value in the clinical application of fibrinolytic enzymes. We sought an in vivo test system fulfilling the following 3 requirements. The experimental clot should be composed of the animal's own blood and should not contain foreign substances like bovine thrombin or bovine fibrinogen with their high profibrinolysin content. The clot should be demonstrated and its subsequent fate observed objectively. A relatively fixed end point should be established for complete dissolution. A modification of the method, reported by Wessler, was found to be satisfactory. With this method, the injection of homologous serum in combination with local vascular stasis leads to the formation of a firm nonadherent clot at the desired site. The formed clot grossly