title: Procoagulant snake venoms have differential effects in animal plasmas: Implications for antivenom testing in animal models.
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.
authors.affiliation: Clinical Toxicology Research Group, University of Newcastle, Newcastle, Australia; South Asian Clinical Toxicology Research Collaboration, University of Peradeniya, Peradeniya, Sri Lanka. Electronic address: kalanapm@gmail.com.
authors.forename: Kalana P
authors.initials: KP
authors.lastname: Maduwage
authors.affiliation: Hunter Haematology Research Group, Calvary Mater Newcastle, Newcastle, NSW, Australia.
authors.forename: Fiona E
authors.initials: FE
authors.lastname: Scorgie
authors.affiliation: Hunter Haematology Research Group, Calvary Mater Newcastle, Newcastle, NSW, Australia.
authors.forename: Lisa F
authors.initials: LF
authors.lastname: Lincz
authors.affiliation: Clinical Toxicology Research Group, University of Newcastle, Newcastle, Australia.
authors.forename: Margaret A
authors.initials: MA
authors.lastname: O'Leary
authors.affiliation: Clinical Toxicology Research Group, University of Newcastle, Newcastle, Australia; South Asian Clinical Toxicology Research Collaboration, University of Peradeniya, Peradeniya, Sri Lanka.
authors.forename: Geoffrey K
authors.initials: GK
authors.lastname: Isbister
mesh_terms: D000818:Animals; D000997:Antivenins / Q000008:administration & dosage*; D001777:Blood Coagulation / Q000187:drug effects*; D001780:Blood Coagulation Tests / Q000379:methods; D002415:Cats; D002417:Cattle; D003029:Coagulants / Q000008:administration & dosage*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical / Q000379:methods; D006168:Guinea Pigs; D006801:Humans; D010949:Plasma / Q000187:drug effects; D011817:Rabbits; D051381:Rats; D012910:Snake Venoms / Q000633:toxicity*; D012911:Snakes; D013552:Swine; D018675:Toxicity Tests / Q000379:methods*
chemical_list: D000997:Antivenins; D003029:Coagulants; D012910:Snake Venoms