Studies on the Production of Intravascular Thrombi and Their Treatment with Fibrinolysin

IT HAS been shown in experimental animalsthat the human fibrinolytic enzyme (plas-minogen activated with streptokinase) will dissolve fresh intravascular thrombi.1"4 Fi-brinolytic agents are also undergoing an ex-tensive clinical trial and the preliminary re-ports which have appeared*"9 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 ther-apy 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 under-taken to investigate, under controlled condi-tions, some of the factors which might de-termine the response to fibrinolytic treatment. It is hoped that the information gained will be of value in the clinical application of fi-brinolytic enzymes. We sought an in vivo test system fulfilling the following 3 requirements. The experimen-tal 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 con-tent.10 The clot should be demonstrated and its subsequent fate observed objectively. A relatively fixed end point should be estab-lished for complete dissolution. A modification of the method, reported by Wessler,11 was found to be satisfactory. With this method, the injection of homologous se-rum in combination with local vascular stasis leads to the formation of a firm nonadherent clot at the desired site. The formed clot grossl