Bleeding and Thrombosis: Insights into Pathophysiology of <i>Bothrops</i> Venom-Related Hemostasis Disorders

Toxins from <i>Bothrops</i> venoms targeting hemostasis are responsible for a broad range of clinical and biological syndromes including local and systemic bleeding, incoagulability, thrombotic microangiopathy and macrothrombosis. Beyond hemostais disorders, toxins are also involved in t...

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Bibliographic Details
Main Authors: Sébastien Larréché, Jean-Philippe Chippaux, Lucie Chevillard, Simon Mathé, Dabor Résière, Virginie Siguret, Bruno Mégarbane
Format: Article
Language:English
Published: MDPI AG 2021-09-01
Series:International Journal of Molecular Sciences
Subjects:
Online Access:https://www.mdpi.com/1422-0067/22/17/9643
Description
Summary:Toxins from <i>Bothrops</i> venoms targeting hemostasis are responsible for a broad range of clinical and biological syndromes including local and systemic bleeding, incoagulability, thrombotic microangiopathy and macrothrombosis. Beyond hemostais disorders, toxins are also involved in the pathogenesis of edema and in most complications such as hypovolemia, cardiovascular collapse, acute kidney injury, myonecrosis, compartmental syndrome and superinfection. These toxins can be classified as enzymatic proteins (snake venom metalloproteinases, snake venom serine proteases, phospholipases A<sub>2</sub> and L-amino acid oxidases) and non-enzymatic proteins (desintegrins and C-type lectin proteins). Bleeding is due to a multifocal toxicity targeting vessels, platelets and coagulation factors. Vessel damage due to the degradation of basement membrane and the subsequent disruption of endothelial cell integrity under hydrostatic pressure and tangential shear stress is primarily responsible for bleeding. Hemorrhage is promoted by thrombocytopenia, platelet hypoaggregation, consumption coagulopathy and fibrin(ogen)olysis. Onset of thrombotic microangiopathy is probably due to the switch of endothelium to a prothrombotic phenotype with overexpression of tissue factor and other pro-aggregating biomarkers in association with activation of platelets and coagulation. Thrombosis involving large-caliber vessels in <i>B. lanceolatus</i> envenomation remains a unique entity, which exact pathophysiology remains poorly understood.
ISSN:1661-6596
1422-0067