Efficacy of antivenom against the procoagulant effect of Australian brown snake (Pseudonaja sp.) venom

In vivo and in vitro studies

Geof Isbister, M O'LEARY, Jennifer Schneider, S BROWN, Bart Currie

Research output: Contribution to journalArticleResearchpeer-review

Abstract

Snake venom induced consumption coagulopathy (VICC) is a common complication of snake bite due to prothrombin activators or thrombin-like enzymes in the venom. This study aimed to determine the efficacy and dose of antivenom for treating VICC in patients envenomed by brown snakes (Pseudonaja spp.), including in vitro coagulation studies. In serial blood samples from patients with brown snake envenoming, venom and antivenom concentrations were measured using enzyme immunoassays. In vitro mixtures of brown snake venom and antivenom were used to investigate antivenom binding, neutralisation of prothrombin activity, prevention of venom-mediated clotting and effect on thrombin generation parameters using a thrombinoscope. In 27 envenomed patients the median venom concentration was 20 ng/mL (Interquartile range[IQR]:12-44 ng/mL) prior to antivenom and was not detected after antivenom administration, including 9 patients given one vial. In vitro, 200 ?g/mL of antivenom bound all free venom at venom concentrations seen in patients. In vitro prothrombinase activity of the venom (using a chromogenic substrate) was not neutralised by antivenom. However, for venom concentrations seen in humans, 100 ?g/mL of antivenom prevented venom clotting activity in human plasma and 479 ?g/mL neutralised procoagulant venom activity measured by triggering thrombin generation. One vial of antivenom appears to be sufficient to bind and neutralise all venom in patients with severe brown snake envenoming. � 2006 Elsevier Ltd. All rights reserved.
Original languageEnglish
Pages (from-to)57-67
Number of pages11
JournalToxicon
Volume49
Issue number1
Publication statusPublished - 2007

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Antivenins
Snakes
Venoms
Snake Venoms
Thrombin
Disseminated Intravascular Coagulation
Prothrombin
In Vitro Techniques
Plasma (human)
Chromogenic Compounds
Snake Bites
Thromboplastin
Enzymes
Coagulation
Immunoenzyme Techniques
Human Activities
Blood

Cite this

Isbister, Geof ; O'LEARY, M ; Schneider, Jennifer ; BROWN, S ; Currie, Bart. / Efficacy of antivenom against the procoagulant effect of Australian brown snake (Pseudonaja sp.) venom : In vivo and in vitro studies. In: Toxicon. 2007 ; Vol. 49, No. 1. pp. 57-67.
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Efficacy of antivenom against the procoagulant effect of Australian brown snake (Pseudonaja sp.) venom : In vivo and in vitro studies. / Isbister, Geof; O'LEARY, M; Schneider, Jennifer; BROWN, S; Currie, Bart.

In: Toxicon, Vol. 49, No. 1, 2007, p. 57-67.

Research output: Contribution to journalArticleResearchpeer-review

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AB - Snake venom induced consumption coagulopathy (VICC) is a common complication of snake bite due to prothrombin activators or thrombin-like enzymes in the venom. This study aimed to determine the efficacy and dose of antivenom for treating VICC in patients envenomed by brown snakes (Pseudonaja spp.), including in vitro coagulation studies. In serial blood samples from patients with brown snake envenoming, venom and antivenom concentrations were measured using enzyme immunoassays. In vitro mixtures of brown snake venom and antivenom were used to investigate antivenom binding, neutralisation of prothrombin activity, prevention of venom-mediated clotting and effect on thrombin generation parameters using a thrombinoscope. In 27 envenomed patients the median venom concentration was 20 ng/mL (Interquartile range[IQR]:12-44 ng/mL) prior to antivenom and was not detected after antivenom administration, including 9 patients given one vial. In vitro, 200 ?g/mL of antivenom bound all free venom at venom concentrations seen in patients. In vitro prothrombinase activity of the venom (using a chromogenic substrate) was not neutralised by antivenom. However, for venom concentrations seen in humans, 100 ?g/mL of antivenom prevented venom clotting activity in human plasma and 479 ?g/mL neutralised procoagulant venom activity measured by triggering thrombin generation. One vial of antivenom appears to be sufficient to bind and neutralise all venom in patients with severe brown snake envenoming. � 2006 Elsevier Ltd. All rights reserved.

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