Slounase a Batroxobin Containing Activated Factor XEffectively Enhances Hemostatic Clot Formation and Reducing Bleedingin Hypocoagulant Conditions in Mice

摘要

Uncontrolled bleeding associated with trauma and surgery is the leadingcause of preventable death. Batroxobin, a snake venom-derivedthrombin-like serine protease, has been shown to clot fibrinogen bycleaving fibrinopeptide A in a manner distinctly different fromthrombin, even in the presence of heparin. The biochemical propertiesof batroxobin and its effect on coagulation have been wellcharacterized in vitro. However, the efficacy ofbatroxobin on hemostatic clot formation in vivo isnot well studied due to the lack of reliable in vivohemostasis models. Here, we studied the efficacy of batroxobin andslounase, a batroxobin containing activated factor X, on hemostaticclot composition and bleeding using intravital microcopy laserablation hemostasis models in micro and macro vessels and liverpuncture hemostasis models in normal and heparin-induced hypocoagulantmice. We found that prophylactic treatment in wild-type mice withbatroxobin, slounase and activated factor X significantly enhancedplatelet-rich fibrin clot formation following vascular injury. Inheparin-treated mice, batroxobin treatment resulted in detectablefibrin formation and a modest increase in hemostatic clot size, whileactivated factor X had no effect. In contrast, slounase treatmentsignificantly enhanced both platelet recruitment and fibrin formation,forming a stable clot and shortening bleeding time and blood loss inwild-type and heparin-treated hypocoagulant mice. Our data demonstratethat, while batroxobin enhances fibrin formation, slounase was able toenhance hemostasis in normal mice and restore hemostasis inhypocoagulant conditions via the enhancement of fibrin formation andplatelet activation, indicating that slounase is more effective incontrolling hemorrhage.