PB1038 - Hemostasis disorders induced by Bothrops atrox and Bothrops lanceolatus venoms: in vivo study

Tuesday, June 25, 2024

13:45 – 14:45 ICT

Room: Exhibition Hall

Co-Author(s)

Sébastien Larréché, MD, PhD

MD, PhD
Hôpital d'instruction des armées Bégin, Université Paris Cité, Inserm UMR-S 1144
Saint-Mandé, Ile-de-France, France
LC

Lucie Chevillard

PhD
Université Paris Cité, Inserm UMR-S 1144
Paris, Ile-de-France, France
SM

Simon Mathé

MD
Université Paris Cité, Inserm UMR-S 1144
Paris, Ile-de-France, France
AS

Aurélie Servonnet

PharmD
Institut de recherche biomédicale des armées
Bretigny-sur-orge, Ile-de-France, France
BJ

Bérangère Joly

PharmD, PhD
Université Paris Cité, EA3518, Hôpital Lariboisière
Paris, Ile-de-France, France
Virginie Siguret

PharmD, PhD
Université Paris Cité, Inserm UMR-S 1140, Hématologie biologique, Hôpital Lariboisière (AP-HP)
Paris, Ile-de-France, France
JC

Jean-Philippe Chippaux

MD, PhD
IRD, Université Paris Cité, UMR 261 MERIT
Paris, Ile-de-France, France
BM

Bruno Mégarbane

MD, PhD
Université Paris Cité, Inserm UMR-S 1144, Hôpital Lariboisière
Paris, Ile-de-France, France

Presenting Author(s)

Georges Jourdi, PharmD, PhD

Associate Professor in haematology
Inserm Research institute
Paris, Ile-de-France, France

Background: Bothrops atrox envenomation in French Guiana may result in a typical Viperidae envenomation resulting in an increased local and systemic bleeding risk while B. lanceolatus envenomation in Martinique may be complicated by multiple systemic infarctions up to 48 h after the snakebite, even in case of moderate envenomation. These opposing clinical effects cannot be explained by composition or comparable in vitro procoagulant activity of these two venoms.

Aims: To compare the effects of B. atrox and B. lanceolatus venoms in rats and identify the determinants of the hemorrhagic versus thrombotic complications.

Methods: Saline (control group), B. atrox or B. lanceolatus venoms were injected by dorsal subcutaneous route in male Sprague-Dawley adult rats. Blood was sampled at H3, H6, or H24 after envenomation from the catheterized abdominal aorta. Whole blood rotational thromboelastometry (ROTEM), platelet count, plasma fibrinogen, thrombin generation and fibrinography assays, endothelial (von Willebrand factor, ADAMTS13 activity, ICAM-1, and soluble E-selectin), and inflammatory biomarkers (IL-1 beta, IL-6, TNF-alpha, MCP-1, and PAI-1) were compared between groups.

Results: Fibrinogen consumption and increased thrombin generation were observed at H3 with the two venoms. Only B. atrox venom induced thrombocytopenia and reduced Rotem clot amplitude. B. lanceolatus venom resulted in a delayed (i.e., 24 hours after injection) increase in fibrin generation combined with elevated inflammatory biomarkers. No endothelial damage was found with either venoms.

Conclusion(s): Mechanisms involved in Bothrops envenomation-induced bleeding and thrombotic complications are not distinct but represent the two sides of the same coin (Figure 1). In the event of major platelet and fibrinogen consumption, hemorrhage may occur early, whereas in case of minor consumption or early restoration of platelet count and fibrinogen level, venom-induced systemic inflammation may increase the risk of late thrombotic complications.