The contrasting effects of Bothrops lanceolatus and Bothrops atrox venom on procoagulant activity and thrombus stability under blood flow conditions

Abstract

Background: Consumption coagulopathy and hemorrhagic syndrome are the typical features of Bothrops sp. snake envenoming. In contrast, B. lanceolatus envenoming can induce thrombotic complications. Our aim was to test whether crude B. lanceolatus and B. atrox venoms would display procoagulant activity and induce thrombus formation under flow conditions. Methods and Principal Findings: Fibrin formation in human plasma was observed for B. lanceolatus venom at 250–1000 ng/mL concentrations, which also induced clot formation in purified human fibrinogen, indicating thrombin-like activity. The degradation of fibrinogen confirmed the fibrinogenolytic activity of B. lanceolatus venom. B. lanceolatus venom displayed consistent thrombin-like and kallikrein-like activity increases in plasma conditions. The well-known procoagulant B. atrox venom activated plasmatic coagulation factors in vitro and induced firm thrombus formation under high shear rate conditions. In contrast, B. lanceolatus venom induced the formation of fragile thrombi that could not resist shear stress. Conclusions: Our results suggest that crude B. lanceolatus venom displays amidolytic activity and can activate the coagulation cascade, leading to prothrombin activation. B. lanceolatus venom induces the formation of an unstable thrombus under flow conditions, which can be prevented by the specific monovalent antivenom Bothrofav®. Key contribution: Crude B. lanceolatus venom displays procoagulant activity and is able to activate coagulation factors in the plasma, independently of its enzymatic activity. Under flow conditions, B. lanceolatus venom elicits the formation of a thrombus that cannot resist shear stress, suggesting thrombus fragility. The specific monovalent antivenom Bothrofav® was able to prevent B. lanceolatus venom-induced thrombus formation.