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Endogenous thrombin potential as a novel method for the characterization of procoagulant snake venoms and the efficacy of antivenom.
Toxicon. 2010 Aug 01; 56(1):75-85.T

Abstract

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+Show Affiliations

Faculty of Health, University of Newcastle, Newcastle, New South Wales, Australia. geoff.isbister@gmail.comNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

20338189

Citation

Isbister, Geoffrey K., et al. "Endogenous Thrombin Potential as a Novel Method for the Characterization of Procoagulant Snake Venoms and the Efficacy of Antivenom." Toxicon : Official Journal of the International Society On Toxinology, vol. 56, no. 1, 2010, pp. 75-85.
Isbister GK, Woods D, Alley S, et al. Endogenous thrombin potential as a novel method for the characterization of procoagulant snake venoms and the efficacy of antivenom. Toxicon. 2010;56(1):75-85.
Isbister, G. K., Woods, D., Alley, S., O'Leary, M. A., Seldon, M., & Lincz, L. F. (2010). Endogenous thrombin potential as a novel method for the characterization of procoagulant snake venoms and the efficacy of antivenom. Toxicon : Official Journal of the International Society On Toxinology, 56(1), 75-85. https://doi.org/10.1016/j.toxicon.2010.03.013
Isbister GK, et al. Endogenous Thrombin Potential as a Novel Method for the Characterization of Procoagulant Snake Venoms and the Efficacy of Antivenom. Toxicon. 2010 Aug 1;56(1):75-85. PubMed PMID: 20338189.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Endogenous thrombin potential as a novel method for the characterization of procoagulant snake venoms and the efficacy of antivenom. AU - Isbister,Geoffrey K, AU - Woods,David, AU - Alley,Steven, AU - O'Leary,Margaret A, AU - Seldon,Michael, AU - Lincz,Lisa F, Y1 - 2010/03/23/ PY - 2010/01/07/received PY - 2010/03/09/revised PY - 2010/03/17/accepted PY - 2010/3/27/entrez PY - 2010/3/27/pubmed PY - 2010/8/3/medline SP - 75 EP - 85 JF - Toxicon : official journal of the International Society on Toxinology JO - Toxicon VL - 56 IS - 1 N2 - 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. SN - 1879-3150 UR - https://www.unboundmedicine.com/medline/citation/20338189/Endogenous_thrombin_potential_as_a_novel_method_for_the_characterization_of_procoagulant_snake_venoms_and_the_efficacy_of_antivenom_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0041-0101(10)00116-9 DB - PRIME DP - Unbound Medicine ER -