In vitro anticoagulant effects of Bungarus venoms on human plasma which are effectively neutralized by the PLA2-inhibitor varespladib

Abstract

Bungarus (krait) envenomings are well-known for their life-threatening neurotoxic effects. However, their impact on coagulation remains largely unexplored experimentally or clinically. This study, examined the effect of begins to examine venoms from four Bungarus species—B. caeruleus, B. candidus, B. fasciatus, and B. flaviceps on human platelet poor plasma coagulation parameters using thromboelastography and coagulation inhibition assays. B. flaviceps completely inhibited clotting, while B. caeruleus only delayed clot formation. In contrast, B. candidus and B. fasciatus did not affect clotting. Subsequent examinations into the anticoagulant biochemical mechanisms demonstrated divergent pathophysiological pathways. B. caeruleus venom anticoagulant effects were prevented by the addition of an excess of phospholipids, with anticoagulation thereby the result of phospholipid depletion. In contrast B. flaviceps anticoagulation was not affected by the addition of an excess of phospholipids. Further investigations demonstrated that B. flaviceps mediates its anticoagulant toxicity through the inactivation of coagulation enzymes. The anticoagulant effects of both B. flaviceps and B. caeruleus were nullified by varespladib, a phospholipase A₂ (PLA₂) inhibitor, revealing the toxin class involved. These results uncover previously unrecognized and unexplored anticoagulant effects of Bungarus venoms.