title: Efficacy of antivenom against the procoagulant effect of Australian brown snake (Pseudonaja sp.) venom: in vivo and in vitro studies.
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 microg/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 microg/mL of antivenom prevented venom clotting activity in human plasma and 479 microg/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.
authors.affiliation: Tropical Toxinology Unit, Menzies School of Health Research, Charles Darwin University, Darwin, NSW, Australia. geoffrey.isbister@menzies.edu.au
authors.forename: Geoffrey K
authors.initials: GK
authors.lastname: Isbister
authors.forename: Margaret A
authors.initials: MA
authors.lastname: O'Leary
authors.forename: Jennifer J
authors.initials: JJ
authors.lastname: Schneider
authors.forename: Simon G A
authors.initials: SG
authors.lastname: Brown
authors.forename: Bart J
authors.initials: BJ
authors.lastname: Currie
mesh_terms: D000818:Animals; D000997:Antivenins / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology* / Q000627:therapeutic use; D001315:Australia; D001777:Blood Coagulation / Q000187:drug effects*; D004546:Elapid Venoms / Q000037:antagonists & inhibitors / Q000097:blood / Q000737:chemistry*; D017815:Elapidae; D006801:Humans; D066298:In Vitro Techniques; D011516:Prothrombin / Q000187:drug effects*; D012909:Snake Bites / Q000097:blood / Q000188:drug therapy
chemical_list: D000997:Antivenins; D004546:Elapid Venoms; D011516:Prothrombin