Procoagulant snake venoms have differential effects in animal plasmas: Implications for antivenom testing in animal models

Kalana P Maduwage; Fiona E Scorgie; Lisa F Lincz; Margaret A O'Leary; Geoffrey K Isbister

doi:10.1016/j.thromres.2015.12.002

Procoagulant snake venoms have differential effects in animal plasmas: Implications for antivenom testing in animal models

Thromb Res. 2016 Jan:137:174-177. doi: 10.1016/j.thromres.2015.12.002. Epub 2015 Dec 2.

Authors

Kalana P Maduwage¹, Fiona E Scorgie², Lisa F Lincz², Margaret A O'Leary³, Geoffrey K Isbister⁴

Affiliations

¹ Clinical Toxicology Research Group, University of Newcastle, Newcastle, Australia; South Asian Clinical Toxicology Research Collaboration, University of Peradeniya, Peradeniya, Sri Lanka. Electronic address: [email protected].
² Hunter Haematology Research Group, Calvary Mater Newcastle, Newcastle, NSW, Australia.
³ Clinical Toxicology Research Group, University of Newcastle, Newcastle, Australia.
⁴ Clinical Toxicology Research Group, University of Newcastle, Newcastle, Australia; South Asian Clinical Toxicology Research Collaboration, University of Peradeniya, Peradeniya, Sri Lanka.

PMID: 26656242
DOI: 10.1016/j.thromres.2015.12.002

Abstract

Background: Animal models are used to test toxic effects of snake venoms/toxins and the antivenom required to neutralise them. However, venoms that cause clinically relevant coagulopathy in humans may have differential effects in animals. We aimed to investigate the effect of different procoagulant snake venoms on various animal plasmas.

Methods: Prothrombin time (PT), activated partial thromboplastin time (aPTT), fibrinogen and D-dimer levels were measured in seven animal plasmas (human, rabbit, cat, guinea pig, pig, cow and rat). In vitro clotting times were then used to calculate the effective concentration (EC50) in each plasma for four snake venoms with different procoagulant toxins: Pseudonaja textilis, Daboia russelli, Echis carinatus and Calloselasma rhodostoma.

Results: Compared to human, PT and aPTT were similar for rat, rabbit and pig, but double for cat and cow, while guinea pig had similar aPTT but double PT. Fibrinogen and D-dimer levels were similar for all species. Human and rabbit plasmas had the lowest EC50 for P. textilis (0.1 and 0.4 μg/ml), D. russelli (0.4 and 0.1 μg/ml), E. carinatus (0.6 and 0.1 μg/ml) venoms respectively, while cat plasma had the lowest EC50 for C. rhodostoma (11 μg/ml) venom. Cow, rat, pig and guinea pig plasmas were highly resistant to all four venoms with EC50 10-fold that of human.

Conclusions: Different animal plasmas have varying susceptibility to procoagulant venoms, and excepting rabbits, animal models are not appropriate to test procoagulant activity. In vitro assays on human plasma should instead be adopted for this purpose.

Publication types

Comparative Study
Evaluation Study
Research Support, Non-U.S. Gov't

MeSH terms

Animals
Antivenins / administration & dosage*
Blood Coagulation / drug effects*
Blood Coagulation Tests / methods
Cats
Cattle
Coagulants / administration & dosage*
Disease Models, Animal*
Dose-Response Relationship, Drug
Drug Evaluation, Preclinical / methods
Guinea Pigs
Humans
Plasma / drug effects
Rabbits
Rats
Snake Venoms / toxicity*
Snakes
Swine
Toxicity Tests / methods*

Substances

Antivenins
Coagulants
Snake Venoms