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.
Resumen
Bothrops jararaca envenomation: Pathogenesis of hemostatic disturbances and intravascular hemolysis.
Por qué esto importa para la hirudoterapia
Este estudio utilizó pretratamiento con warfarina para agotar los factores de la coagulación dependientes de vitamina K en ratas, con el fin de diseccionar las contribuciones relativas de los activadores de protrombina, los activadores del factor X y las enzimas tipo trombina del veneno de Bothrops jararaca a las alteraciones hemostáticas y la hemólisis intravascular. El pretratamiento con warfarina previno la hemólisis intravascular y el consumo de fibrinógeno, pero no previno la trombocitopenia, lo que indica que la generación intravascular de trombina desempeña el papel principal en la coagulopatía y la hemólisis, pero no en la trombocitopenia, y que las fibrinogenasas metaloproteasas pueden contribuir más a la coagulopatía que las enzimas tipo trombina. Para el ámbito de la ASH, la relevancia es indirecta: el estudio examina la generación de trombina y la fisiopatología de las enzimas tipo trombina del veneno de serpiente, lo que conceptualmente se intersecta con los mecanismos anticoagulantes relevantes para la hirudoterapia. Sin embargo, no intervienen sanguijuelas ni sustancias derivadas de sanguijuela, el estudio es preclínico (modelo en rata) y se centra en la patogénesis de la intoxicación por envenenamiento en lugar de la aplicación terapéutica.
Citación
Bothrops jararaca envenomation: Pathogenesis of hemostatic disturbances and intravascular hemolysis
Senise LV et al. · Experimental biology and medicine, 2015
Contexto clínico relacionado
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Añadido a la biblioteca ASH: May 27, 2026 · Última actualización del sitio: 18 de junio de 2026