The Application of a Defibrinogenating Snake Venom Enzyme in Experimental Tumor Metastasis

The thrombin like enzyme (crotalase) has been purified from the venom of the eastern diamond-back rattlesnake (Crotalus adamanteus) (Markland and Damus, 1971). Crotalase is a single chain glycoprotein with a molecular weight of 33,000. The enzyme clots purified fibrinogen, plasma, and plasma anticoagulated with EDTA, citrate or heparin (Markland and Pirkle, 1977a). In contrast to thrombin, crotalase cleaves only fibrinopeptides A from fibrinogen (Markland and Pirkle, 1977b). In vivo studies have shown that when purified crotalase is infused into animals a benign state of defibrinogenation results. There is no fibrin deposition in internal organs, disseminated intravascular coagulation does not occur, and there are minimal changes in clotting factors during defibrinogenation. Crotalase apparently attacks fibrinogen directly, forming soluble fibrin monomers or abnormal fibrin microclots which are rapidly removed by secondary activation of the fibrinolytic system and/or by the reticuloendothelial system. Separate studies have shown that crotalase neither activates the fibrinolytic system nor is fibrinolytic itself at the levels used for defibrinogenation (Damus et al., 1972).