Bothrops atrox and Bothrops lanceolatus Venoms In Vitro Investigation: Composition, Procoagulant Effects, Co-Factor Dependency, and Correction Using Antivenoms

Toxins (Basel). 2023 Oct 16;15(10):614. doi: 10.3390/toxins15100614.

Abstract

Bothrops venoms are rich in enzymes acting on platelets and coagulation. This action is dependent on two major co-factors, i.e., calcium and phospholipids, while antivenoms variably neutralize venom-related coagulopathy effects. Our aims were (i) to describe the composition of B. atrox and B. lanceolatus venoms; (ii) to study their activity on the whole blood using rotational thromboelastometry (ROTEM); (iii) to evaluate the contribution of calcium and phospholipids in their activity; and (iv) to compare the effectiveness of four antivenoms (Bothrofav, Inoserp South America, Antivipmyn TRI, and PoliVal-ICP) on the procoagulant activity of these two venoms. Venom composition was comparable. Both venoms exhibited hypercoagulant effects. B. lanceolatus venom was completely dependent on calcium but less dependent on phospholipids than B. atrox venom to induce in vitro coagulation. The four antivenoms neutralized the procoagulant activity of the two venoms; however, with quantitative differences. Bothrofav was more effective against both venoms than the three other antivenoms. The relatively similar venom-induced effects in vitro were unexpected considering the opposite clinical manifestations resulting from envenomation (i.e., systemic bleeding with B. atrox and thrombosis with B. lanceolatus). In vivo studies are warranted to better understand the pathophysiology of systemic bleeding and thrombosis associated with Bothrops bites.

Keywords: Bothrops; ROTEM; antivenom; co-factor; coagulation; venom composition.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antivenins / pharmacology
  • Bothrops*
  • Calcium
  • Crotalid Venoms* / toxicity
  • Hemorrhage / chemically induced
  • Hemorrhage / drug therapy
  • Snake Bites*
  • Thrombosis*

Substances

  • Antivenins
  • Calcium
  • Crotalid Venoms

Supplementary concepts

  • Bothrops lanceolatus

Grants and funding

This research was in part funded by the Agence Nationale de la Recherche (ANR), Mitobothrops Grant ANR-18-CE17-0026 (https://anr.fr/Project-ANR-18-CE17-0026 (accessed on 14 August 2023)).