Venoms and toxins that induce anticoagulation in vitro do not cause major alterations in coagulation parameters in vivo in a mouse model.

Snake venoms exert profound effects on blood coagulation, mostly associated with consumption coagulopathy due to the procoagulant activity of venom proteinases, which result in drastic alterations of laboratory clotting tests. In addition, snake venoms contain enzymes [mostly phospholipases A2 (PLA2s) and metalloproteinases (SVMPs)] that have strong anticoagulant activity in vitro. However, their actual effect on coagulation parameters in vivo has not been studied in detail. In the present work, we evaluated the alterations in standard clotting tests (prothrombin time, activated partial thromboplastin time and fibrinogen concentration) and in rotational thromboelastometry parameters after the administration of venoms (Naja nigricollis and Pseudechis papuanus) and enzymes (P-I and P-III fibrinogenolytic SVMPs and an anticoagulant PLA2) that exert anticoagulant effect in vitro. For comparative purposes the venom of Bothrops asper, which is procoagulant in vitro and induces defibrinogenation in vivo, was also studied. Venoms and enzymes were administered intravenously in mice using sublethal doses to assess their in vivo effects on clotting parameters. Despite their anticoagulant effect on mouse plasma in vitro, the alterations of the clotting tests in vivo were generally limited, being more pronounced in the case of P. papuanus venom and in some Intem and Fibtem parameters. In contrast, the venom of B. asper induced a consumption coagulopathy associated with drastic alterations in all clotting parameters examined. Our observations suggest that venom components that induce anticoagulation in vitro do not necessarily exert major alterations in clotting parameters in vivo.