Efficacy and Potency of Antivenoms in Neutralizing the Procoagulant Effects of Australian Snake Venoms in Dog and Human Plasma

Abstract

The efficacy and potency of Commonwealth Serum Laboratories (CSL) snake antivenoms in neutralizing the procoagulant action of Australian snake venoms was studied in vitro. The procoagulant action of venoms from Tiger, Brown and Taipan Snakes were measured in pooled canine or pooled human plasma. Mixtures of the venoms and their appropriate antivenoms, ranging from 0.1 to 15 times the recommended neutralizing dose of antivenom were then added to pooled canine or pooled human plasma and the efficacy and potency of the antivenoms in preventing the procoagulant action was measured. Neutralization was achieved by the addition of the appropriate antivenom in concentrations of 0.5 (Taipan), 10 (Tiger), 10 (Gwardar), 15 (Dugite) and an estimated 20 (Common Brown) times the dose expected. Similar results were obtained in canine and human plasma. The potency of Tiger and especially Brown Snake antivenom is substantially lower (10–20 times) than that predicted by CSL. These findings support an increase in the dose of antivenom to be used for the treatment of Tiger and especially Brown Snake envenomation complicated by coagulopathy. The in vitro canine model may be suitable for studying the procoagulant effects of Australian snake venoms.

Clinical Effects and Antivenom Dosing in Brown Snake (Pseudonaja spp.) Envenoming — Australian Snakebite Project (ASP-14)

“…[5], [7], [8], [29], [30] This case series supports that the much higher doses recommended previously are unnecessary and indeed shows that one vial of brown snake antivenom was sufficient, with similar recovery and outcomes compared with patients receiving larger doses. This is consistent with recent in vitro studies showing that one vial binds all circulating venom up to a concentration of 100 ng/ml [7] and will neutralise the procoagulant effects.…”

“…[31] However, even if brown snakes delivered 10 times the CSL calculated average venom yield, one vial should still be sufficient based on recent in vitro clotting studies. [7], [27] Unlike older animal work suggesting larger antivenom doses, [29], [32] these studies used venom at clinically relevant concentrations and show neutralisation of venom concentrations measured in this clinical study, with antivenom concentrations equivalent to dosing with one vial. [7], [27].…”

Suspected snakebite: One year prospective study of emergency department presentations

“…This is a particular problem with brown snake ( Pseudonaja spp.) envenoming in most parts of Australia where much larger doses are being required than what was initially recommended by the manufacturer 27,28 . Although there were only two cases of brown snake envenoming in this series, they both required greater than four ampoules of brown snake AV.…”

Venom yields from Australian and some other species of snakes

“…More rapid immobilization by the venom through increased yield, would minimize injury to the snake. Given the reported problems of CSL Ltd Brown snake antivenom in neutralizing the procoagulant toxin fraction of Pseudonaja venoms which induces blood coagulation (Tibballs and Sutherland 1991;Sprivulis et al 1996;Masci et al 1998;Judge et al 2006) and small molecular weight toxins, the implications of these results suggest that if there is no change to the efficacy of the antivenom serum, further consideration be given to both the quantity of antivenom in the vial and the initial dose. The amount of antivenom present in vials of Australian antivenoms (CSL Ltd) is related to the average amount of venom produced when the snakes are milked (Sutherland and Tibballs 2001).…”