Intravenous Trypsin: Its Anticoagulant, Fibrinolytic and Thrombolytic Effects 1

Abstract

Fibrinogenolysis and prolonged blood coagulation have been observed following large intravenous doses of crystalline trypsin ( 1 ) .2 The present study was undertaken to evaluate further the effects of intravenous crystalline trypsin upon the protein components of the coagulation mechanism and the fibrin content of artificially induced intravascular thrombi, in 60 rabbits and 25 dogs. A striking observation in this study was the lack of untoward reactions, including shock, when the rate and concentration of injected trypsin were kept within carefully calculated limits. MATERIALS 1) Sixty rabbits whose average weight was 2 kg. were fed rabbit food pellets and given water ad libitum.2 Quick (2). Fibrinogen was determined by the method of Greenberg (3). The Innerfield, Angrist, and Benjamin method (4) of antithrombin titer determination was used. Factor V was measured by the method of Stefanini (5); and fibrinolysis assay was made by the Conley, Ratnoff, and Hartmann method (6). Determinations of coagulation time were made by the Lee-White method (7). Blood volume was estimated following administration of labeled albumin (8). Continuous measurements of clotting viscosities were made with a RichRoth Ultra-viscosimeter (9). PROCEDURE 1) Rabbits. Blood samples were obtained from non-anesthetized rabbits by cardiac puncture, before and at varying intervals during infusion of trypsin. Sections of an ear vein thrombus were obtained for histologic study prior to, during, and after completion of each intravenous infusion.2) Dogs. Trypsin infusions were given to dogs who had been anesthetized with 6 per cent Nembutal. Blood samples were obtained prior to, and during the course of the infusion. In securing 1049

The Fibrinolytic Activity of Streptokinase Activated Human Plasmin 1

“…Prepared by the method of Kline (8). This 4 or fresh plasma were used as sources of bovine plasminogen.…”

“…This is a chloroform activated enzyme derived from bovine plasma (13). 4 (15). Although this preparation contained traces of human plasminogen, the contamination was not significant enough to influence the fibrinolytic assay.…”

The Enzymatic Dissolution Of Experimental Arterial Thrombi in the Dog by Trypsin, Chymotrypsin and Plasminogen Activators12

“…A number of investigators have undertaken studies on the dissolution of intravascular thrombi and emboli by enzymes capable of effecting the dissolution of blood clots in vitro (1)(2)(3)(4). Two types of approach have been used; the direct-introduction of a proteolytic enzyme capable of digesting fibrin (2,3), and activation of the naturally occurring proteolytic and fibrinolytic enzyme of mammalian plasma by the injection of a specific kinase (1).…”

“…Two types of approach have been used; the direct-introduction of a proteolytic enzyme capable of digesting fibrin (2,3), and activation of the naturally occurring proteolytic and fibrinolytic enzyme of mammalian plasma by the injection of a specific kinase (1). This latter approach is based on the observation that plasma contains a proenzyme termed plasminogen (5) or profibrinolysin (6), which, when activated, is converted to plasmin or fibrinolysin, a proteolytic enzyme with an affinity for fibrin (7).…”

“…Recent reports have appeared on the successful liquefaction of intravascular clots in rabbit ear veins by the intravenous infusion of large amounts of streptokinase (1); the lysis of venous clots in rabbits and dogs by the intravenous administration of large amounts of trypsin (2); and the dissolution of venous thrombi in rabbits and dogs by injections of purified human plasmin (previously activated in vitro by streptokinase) (3).…”