De Novo Assessment and Review of Pan-American Pit Viper Anticoagulant and Procoagulant Venom Activities via Kinetomic Analyses
Review published in Toxins (2019)
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.
Abstract sourced from PubMed (NCBI) for the cited record. See the original publication for the authoritative version.
Summary
De Novo Assessment and Review of Pan-American Pit Viper Anticoagulant and Procoagulant Venom Activities via Kinetomic Analyses.
Why This Matters for Hirudotherapy
This review and prospective laboratory study characterized the coagulopathic activities (anticoagulant, thrombin-like, and thrombin-generating) of thirty-two Pan-American pit viper venoms using thrombelastographic methods in human plasma, and assessed whether carbon monoxide or O-phenylhydroxylamine modulate putative heme groups on venom enzymes. North and Central American venoms were predominantly anticoagulant with some thrombin-like activities, while South American Bothrops species primarily exhibited thrombin-generating activity; nearly all assessed activities were heme-modulated. For ASH's domain, the relevance is indirect: the study examines snake venom enzymes with thrombin-like or thrombin-generating activities, which are conceptually related to but biologically distinct from leech-derived thrombin inhibitors such as hirudin. No leeches, leech secretome components, or hirudotherapy are involved. The study is a combination of in-vitro laboratory work and review, with no direct bearing on clinical hirudotherapy practice.
Citation
De Novo Assessment and Review of Pan-American Pit Viper Anticoagulant and Procoagulant Venom Activities via Kinetomic Analyses
Nielsen VG et al. · Toxins, 2019
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