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Bothrops venom-induced hemostasis disorders in the rat: Between Scylla and Charybdis.
PLOS Neglected Tropical Diseases ( IF 3.8 ) Pub Date : 2023-11-27 , DOI: 10.1371/journal.pntd.0011786
Sébastien Larréché 1, 2 , Lucie Chevillard 1 , Georges Jourdi 3, 4 , Simon Mathé 1 , Aurélie Servonnet 5 , Bérangère S Joly 3, 6 , Virginie Siguret 3, 4 , Jean-Philippe Chippaux 7 , Bruno Mégarbane 1, 8
Affiliation  

Hemostasis impairment represents the most threatening consequence of Viperidae envenoming, notably with Bothrops genus. In the French departments of America, B. atrox envenomation in French Guiana may lead to bleeding while B. lanceolatus envenomation in Martinique to thrombosis. Bleeding related to B. atrox envenomation is attributed to vascular damage mediated by venom metalloproteinases and blood uncoagulable state resulting from thrombocytopenia and consumptive coagulopathy. Thrombosis related to B. lanceolatus envenomation are poorly understood. We aimed to compare the effects of B. atrox and B. lanceolatus venoms in the rat to identify the determinants of the hemorrhagic versus thrombotic complications. Viscoelastometry (ROTEM), platelet count, plasma fibrinogen, thrombin generation assay, fibrinography, endothelial (von Willebrand factor, ADAMTS13 activity, ICAM-1, and soluble E-selectin), and inflammatory biomarkers (IL-1β, IL-6, TNF-α, MCP-1, and PAI-1) were determined in blood samples obtained at H3, H6, and H24 after the subcutaneous venom versus saline injection. In comparison to the control, initial fibrinogen consumption was observed with the two venoms while thrombocytopenia and reduction in the clot amplitude only with B. atrox venom. Moreover, we showed an increase in thrombin generation at H3 with the two venoms, an increase in fibrin generation accompanied with hyperfibrinogenemia at H24 and an increase in inflammatory biomarkers with B. lanceolatus venom. No endothelial damage was found with the two venoms. To conclude, our data support two-sided hemostasis complications in Bothrops envenoming with an initial risk of hemorrhage related to platelet consumption and hypocoagulability followed by an increased risk of thrombosis promoted by the activated inflammatory response and rapid-onset fibrinogen restoration.

中文翻译:

波托罗普斯毒液引起的大鼠止血障碍:Scylla 和 Charybdis 之间。

止血障碍是蝰蛇科毒液(尤其是蝰蛇属)中毒最严重的后果。在美洲的法属省,法属圭亚那的 B. atrox 中毒可能导致出血,而马提尼克岛的 B. lanceolatus 中毒则可能导致血栓。与 B. atrox 中毒有关的出血归因于毒液金属蛋白酶介导的血管损伤以及血小板减少症和消耗性凝血病导致的血液不凝固状态。与矛状芽孢杆菌中毒相关的血栓形成知之甚少。我们的目的是比较 B. atrox 和 B. lanceolatus 毒液对大鼠的影响,以确定出血性并发症与血栓性并发症的决定因素。粘弹性测定 (ROTEM)、血小板计数、血浆纤维蛋白原、凝血酶生成测定、纤维蛋白造影、内皮细胞(血管性血友病因子、ADAMTS13 活性、ICAM-1 和可溶性 E-选择素)和炎症生物标志物(IL-1β、IL-6、TNF) -α、MCP-1 和 PAI-1) 在皮下毒液与盐水注射后的 H3、H6 和 H24 获得的血液样本中进行测定。与对照相比,两种毒液观察到初始纤维蛋白原消耗,而仅使用 B. atrox 毒液观察到血小板减少和凝块幅度降低。此外,我们发现,两种毒液在 H3 时凝血酶生成增加,在 H24 时纤维蛋白生成增加并伴有高纤维蛋白原血症,并且使用 B. lanceolatus 毒液炎症生物标志物增加。两种毒液均未发现内皮损伤。总之,我们的数据支持双侧止血并发症,最初与血小板消耗和低凝相关的出血风险,随后由激活的炎症反应和快速发生的纤维蛋白原恢复促进血栓形成的风险增加。
更新日期:2023-11-27
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