The effect of fibrinolytic enzyme FIIa from Agkistrodon acutus venom on disseminated intravascular coagulation in rabbits

A novel fibrinolytic enzyme, FIIa, was isolated from Agkistrodon acutus venom, which can degrade fibrin/fibrinogen and dissolve thrombus without activating plasminogen or influencing the activities of tissue plasminogen activator (t-PA) and plasminogen activator inhibitor type-1 (PAI-1). In this study, we evaluated the effect of FIIa on lipopolysaccharide (LPS)-induced experimental disseminated intravascular coagulation (DIC) in rabbits, through the continuous infusion of 100-μg/kg/h LPS for a period of 6 h. Seven groups were established: LPS control, FIIa (0.1, 0.3, and 0.6 mg/kg/h, respectively), heparin control (100 IU/kg/h), heparin + FIIa (heparin 100 IU/kg/h associated with FIIa 0.3 mg/kg/h), and a saline control group. A continuous injection of LPS induced a gradual impairment in hemostatic parameters, kidney fibrin deposition, and a high mortality rate. The intravenous administration of FIIa improved the concentration of fibrinogen, the activities of protein C, plasminogen, t-PA, antithrombin III (ATIII), and PAI-1. Kidney fibrin deposition and the mortality also decreased. In the in vitro experiments, FIIa can degrade fibrin/fibrinogen and high-dose FIIa enhanced the activity of protein C. These findings suggest that the effects of FIIa on LPS-induced DIC were from fibrinogen degradation and enhanced protein C activity. The simultaneous administration of FIIa and heparin further improved all the hemostatic parameters, including decreased kidney fibrin deposition, and none of the rabbits died within 24 h, which indicates that the effects were mediated by degradation of fibrin/fibrinogen together with thrombin inhibition. We conclude that FIIa may be useful in the treatment of DIC.