Bothrops jararaca envenomation: Pathogenesis of hemostatic disturbances and intravascular hemolysis
Research article published in Experimental biology and medicine (2015)
Abstract
To attain fully functional biological activity, vitamin-K dependent coagulation factors (VKDCF) are γ-carboxylated prior to secretion from liver. Warfarin impairs the γ-carboxylation, and consequently their physiological function. Bothrops jararaca snake venom (BjV) contains several activators of blood coagulation, especially procoagulant enzymes (prothrombin and factor X activators) and thrombin-like enzymes. In order to clarify the relative contribution of prothrombin and factor X activators to the hemostatic disturbances occurring during experimental B. jararaca envenomation, warfarin was used to deplete VKDCF, prior to BjV administration. Male Wistar rats were pretreated with saline (Sal) or warfarin (War) and inoculated subsequently with BjV or saline, thus forming four groups: Sal + Sal (negative control), Sal + BjV (positive control), War + Sal (warfarinization control), and War + BjV. Three hours after inoculation, prothrombin and factor X levels fell 40% and 50%, respectively; levels of both factors decreased more than 97% in the War + Sal and War + BjV groups. Platelet counts dropped 93% and 76% in Sal + BjV and War + BjV, respectively, and plasma fibrinogen levels decreased 86% exclusively in Sal + BjV. After 6 and 24 h, platelet counts and fibrinogen levels increased progressively. A dramatic augmentation in plasma hemoglobin levels and the presence of schizocytes and microcytes in the Sal + BjV group indicated the development of intravascular hemolysis, which was prevented by warfarin pretreatment. Our findings show that intravascular thrombin generation has the foremost role in the pathogenesis of coagulopathy and intravascular hemolysis, but not in the development of thrombocytopenia, in B. jararaca envenomation in rats; in addition, fibrinogenases (metalloproteinases) may contribute to coagulopathy more than thrombin-like enzymes.
Abstract sourced from PubMed (NCBI) for the cited record. See the original publication for the authoritative version.
Zusammenfassung
Bothrops jararaca envenomation: Pathogenesis of hemostatic disturbances and intravascular hemolysis.
Warum dies für die Hirudotherapie relevant ist
This study used warfarin pretreatment to deplete vitamin-K-dependent coagulation factors in rats in order to dissect the relative contributions of prothrombin activators, factor X activators, and thrombin-like enzymes from Bothrops jararaca venom to hemostatic disturbances and intravascular hemolysis. Warfarin pretreatment prevented intravascular hemolysis and fibrinogen consumption but did not prevent thrombocytopenia, indicating that intravascular thrombin generation plays the foremost role in coagulopathy and hemolysis but not in thrombocytopenia, and that metalloproteinase fibrinogenases may contribute more to coagulopathy than thrombin-like enzymes. For ASH's domain, the relevance is indirect: the study examines thrombin generation and thrombin-like enzyme pathophysiology from snake venom, which conceptually intersects with the anticoagulant mechanisms relevant to hirudotherapy. However, no leeches or leech-derived substances are involved, the study is preclinical (rat model), and the focus is envenomation pathogenesis rather than therapeutic application.
Zitation
Bothrops jararaca envenomation: Pathogenesis of hemostatic disturbances and intravascular hemolysis
Senise LV et al. · Experimental biology and medicine, 2015
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