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

Abstract

<p><i>Background:</i> 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.</p><p><i>Methods:</i> 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). <i>In vitro</i> clotting times were then used to calculate the effective concentration (EC₅₀) in each plasma for four snake venoms with different procoagulant toxins: <i>Pseudonaja textilis, Daboia russelli, Echis carinatus</i> and <i>Calloselasma rhodostoma</i>.</p><p><i>Results:</i> 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. <i>textilis</i> (0.1 and 0.4 μg/ml), D. <i>russelli</i> (0.4 and 0.1 μg/ml), E. <i>carinatus</i> (0.6 and 0.1 μg/ml) venoms respectively, while cat plasma had the lowest EC₅₀ for C. <i>rhodostoma</i> (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.</p><p><i>Conclusions:</i> Different animal plasmas have varying susceptibility to procoagulant venoms, and excepting rabbits, animal models are not appropriate to test procoagulant activity. <i>In vitro</i> assays on human plasma should instead be adopted for this purpose.</p>