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Toxins 2019, 11(2), 94; https://doi.org/10.3390/toxins11020094

De Novo Assessment and Review of Pan-American Pit Viper Anticoagulant and Procoagulant Venom Activities via Kinetomic Analyses

1
Department of Anesthesiology, University of Arizona College of Medicine, Tucson, AZ 85719, USA
2
Mtoxins, 1111 Washington Ave, Oshkosh, WI 54901, USA
*
Author to whom correspondence should be addressed.
Received: 14 December 2018 / Revised: 25 January 2019 / Accepted: 2 February 2019 / Published: 6 February 2019
(This article belongs to the Special Issue Assessment of Animal Toxin Function with Novel Viscoelastic Methods)
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Abstract

Snakebite with hemotoxic venom continues to be a major source of morbidity and mortality worldwide. Our laboratory has characterized the coagulopathy that occurs in vitro in human plasma via specialized thrombelastographic methods to determine if venoms are predominantly anticoagulant or procoagulant in nature. Further, the exposure of venoms to carbon monoxide (CO) or O-phenylhydroxylamine (PHA) modulate putative heme groups attached to key enzymes has also provided mechanistic insight into the multiple different activities contained in one venom. The present investigation used these techniques to characterize fourteen different venoms obtained from snakes from North, Central, and South America. Further, we review and present previous thrombelastographic-based analyses of eighteen other species from the Americas. Venoms were found to be anticoagulant and procoagulant (thrombin-like activity, thrombin-generating activity). All prospectively assessed venom activities were determined to be heme-modulated except two, wherein both CO and its carrier molecule were found to inhibit activity, while PHA did not affect activity (Bothriechis schlegelii and Crotalus organus abyssus). When divided by continent, North and Central America contained venoms with mostly anticoagulant activities, several thrombin-like activities, with only two thrombin-generating activity containing venoms. In contrast, most venoms with thrombin-generating activity were located in South America, derived from Bothrops species. In conclusion, the kinetomic profiles of venoms obtained from thirty-two Pan-American Pit Viper species are presented. It is anticipated that this approach will be utilized to identify clinically relevant hemotoxic venom enzymatic activity and assess the efficacy of locally delivered CO or systemically administered antivenoms. View Full-Text
Keywords: hemotoxic venom; prothrombin activator; thrombin-like activity; fibrinogenolytic activity; carbon monoxide; heme; metheme; thrombelastography hemotoxic venom; prothrombin activator; thrombin-like activity; fibrinogenolytic activity; carbon monoxide; heme; metheme; thrombelastography
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).
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Nielsen, V.G.; Frank, N.; Afshar, S. De Novo Assessment and Review of Pan-American Pit Viper Anticoagulant and Procoagulant Venom Activities via Kinetomic Analyses. Toxins 2019, 11, 94.

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