Bothrops jararaca envenomation: Pathogenesis of hemostatic disturbances and intravascular hemolysis

Author(s)

Senise, Luana V. ^{[1, 2]} ; Yamashita, Karine M. ^{[1, 3]} ; Santoro, Marcelo L. ^{[1, 3]}

Affiliation

^[1] Inst Butantan, Lab Pathophysiol, BR-05503900 Sao Paulo - Brazil

^[2] Univ Sao Paulo, Biosci Inst, Dept Physiol, BR-05508900 Sao Paulo - Brazil

^[3] Univ Sao Paulo, Sch Med, Dept Clin Med, BR-05508900 Sao Paulo - Brazil

• Document type: Journal article
• Source: Experimental Biology and Medicine; v. 240, n. 11, p. 1528-1536, NOV 2015.
• Web of Science Citations: 10

Abstract

To attain fully functional biological activity, vitamin-K dependent coagulation factors (VKDCF) are -carboxylated prior to secretion from liver. Warfarin impairs the -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 24h, 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. (AU)

• FAPESP's process: 08/02996-8 - Venoms from neonate and mature Bothrops jararaca snakes: comparison between enzymatic and biological activities, immunoneutralization, chemical composition and ability to induce hemostatic disorders
• Grantee: Marcelo Larami Santoro
• Support Opportunities: Regular Research Grants
• FAPESP's process: 10/08162-1 - Contribution of local injury evoked by Bothrops jararaca snake venom to the genesis of systemic hemostatic disturbances
• Grantee: Marcelo Larami Santoro
• Support Opportunities: Regular Research Grants