Document Detail


Endogenous thrombin potential as a novel method for the characterization of procoagulant snake venoms and the efficacy of antivenom.
MedLine Citation:
PMID:  20338189     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Venom-induced consumption coagulopathy occurs in snake envenoming worldwide but the interaction between procoagulant snake venoms and human coagulation remains poorly understood. We aimed to evaluate an assay using endogenous thrombin potential (ETP) to investigate the procoagulant properties of a range of Australian whole venoms in human plasma and compared this to traditional clotting and prothrombinase activity studies. We developed a novel modification of ETP using procoagulant snake venoms to trigger thrombin production. This was used to characterise the relative potency, calcium and clotting factor requirements of five important Australian snake venoms and efficacy of commercial antivenom, and compared this to prothrombinase activity and clotting assays. All five venoms initiated thrombin generation in the absence and presence of calcium. Pseudonaja textilis (Brown snake; p<0.0001), Hoplocephalus stephensii (Stephen's-banded snake; p<0.0001) and Notechis scutatus (tiger snake; p=0.0073) all had statistically significant increases in ETP with calcium. Venom potency varied between assays, with ETP ranging from least potent with Oxyuranus scutellatus (Taipan) venom to intermediate with N. scutatus and H. stephensii venoms to most potent with P. textilis and Tropidechis carinatus (Rough-scale snake) venoms. ETPs for N. scutatus, T. carinatus and H. stephensii venoms were severely reduced with factor V deficient plasma. Antivenom neutralized the thrombin generating capacity but not prothrombin substrate cleaving ability of the venoms. Contrary to previous studies using clotting tests and factor Xa substrates, these venoms differ in calcium requirement. ETP is a useful assay to investigate mechanisms of other procoagulant venoms and is a robust method of assessing antivenom efficacy.
Authors:
Geoffrey K Isbister; David Woods; Steven Alley; Margaret A O'Leary; Michael Seldon; Lisa F Lincz
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-03-23
Journal Detail:
Title:  Toxicon : official journal of the International Society on Toxinology     Volume:  56     ISSN:  1879-3150     ISO Abbreviation:  Toxicon     Publication Date:  2010 Aug 
Date Detail:
Created Date:  2010-05-03     Completed Date:  2010-08-02     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  1307333     Medline TA:  Toxicon     Country:  England    
Other Details:
Languages:  eng     Pagination:  75-85     Citation Subset:  IM    
Copyright Information:
Crown Copyright 2010. Published by Elsevier Ltd. All rights reserved.
Affiliation:
Faculty of Health, University of Newcastle, Newcastle, New South Wales, Australia. geoff.isbister@gmail.com
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MeSH Terms
Descriptor/Qualifier:
Anticoagulants / administration & dosage,  pharmacology*
Antivenins / administration & dosage,  pharmacology*
Australia
Blood Coagulation / drug effects
Calcium / metabolism
Coagulants / toxicity*
Disseminated Intravascular Coagulation / chemically induced,  physiopathology
Drug Dosage Calculations
Elapid Venoms / enzymology,  metabolism,  toxicity
Enzyme Activation / drug effects
Humans
Kinetics
Prothrombin / antagonists & inhibitors,  metabolism*,  pharmacology
Reptilian Proteins / antagonists & inhibitors,  metabolism*
Serine Endopeptidases / metabolism
Snake Bites / drug therapy
Snake Venoms / enzymology,  toxicity*
Substrate Specificity
Thromboplastin / antagonists & inhibitors,  metabolism*
Chemical
Reg. No./Substance:
0/Anticoagulants; 0/Antivenins; 0/Coagulants; 0/Elapid Venoms; 0/Reptilian Proteins; 0/Snake Venoms; 0/trocarin; 7440-70-2/Calcium; 9001-26-7/Prothrombin; 9035-58-9/Thromboplastin; EC 3.4.21.-/Serine Endopeptidases; EC 3.4.21.-/prothrombin activator protease, Pseudonaja textilis; EC 3.4.21.60/scutelarin

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