Patients bitten by snakes consistently manifest a bleeding tendency, in which thrombocytopenia, consumption coagulopathy, mucous bleeding, and, more rarely, thrombotic microangiopathy, are observed. Von Willebrand factor (VWF) is required for primary hemostasis, and some venom proteins, such as botrocetin (a C-type lectin-like protein) and snake venom metalloproteinases (SVMP), disturb the normal interaction between platelets and VWF, possibly contributing to snakebite-induced bleedings. To understand the relationship among plasma VWF, platelets, botrocetin and SVMP from Bothrops jararaca snake venom (BjV) in the development of thrombocytopenia, we used (a) Wistar rats injected s.c. with BjV preincubated with anti-botrocetin antibodies (ABA) and/or Na2-EDTA (a SVMP inhibitor), and (b) VWF knockout mice (Vwf-/-) injected with BjV. Under all conditions, BjV induced a rapid and intense thrombocytopenia. In rats, BjV alone reduced the levels of VWF:Ag, VWF:CB, high molecular weight multimers of VWF, ADAMTS13 activity, and factor VIII. Moreover, VWF:Ag levels in rats that received BjV preincubated with Na2-EDTA and/or ABA tended to recover faster. In mice, BjV caused thrombocytopenia in both Vwf-/- and C57BL/6 (background control) strains, and VWF:Ag levels tended to decrease in C57BL/6, demonstrating that thrombocytopenia was independent of the presence of plasma VWF. These findings showed that botrocetin present in BjV failed to affect the extent or the time course of thrombocytopenia induced by envenomation, but it contributed to decrease the levels and function of plasma VWF. Thus, VWF alterations during B. jararaca envenomation are an ancillary event, and not the main mechanism leading to decreased platelet counts.

中文翻译：

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von Willebrand 因子和 botrocetin 参与了 Bothrops jararaca 蛇毒诱导的血小板减少症。

被蛇咬伤的患者一贯表现出出血倾向，其中观察到血小板减少症、消耗性凝血病、粘液出血，以及更罕见的血栓性微血管病。血管性血友病因子 (VWF) 是初级止血所必需的，并且一些毒液蛋白，例如 botrocetin（一种 C 型凝集素样蛋白）和蛇毒金属蛋白酶 (SVMP)，会干扰血小板和 VWF 之间的正常相互作用，可能有助于蛇咬伤引起的出血。为了了解来自 Bothrops jararaca 蛇毒 (BjV) 的血浆 VWF、血小板、Botrocetin 和 SVMP 在血小板减少症发生过程中的关系，我们使用了 (a) Wistar 大鼠皮下注射 BjV，其中 BjV 与抗 botrocetin 抗体 (ABA) 和/或Na2-EDTA（一种 SVMP 抑制剂）和（b）注射了 BjV 的 VWF 基因敲除小鼠（Vwf-/-）。在所有条件下，BjV 都会引起快速而剧烈的血小板减少症。在大鼠中，BjV 单独降低 VWF:Ag、VWF:CB、VWF 的高分子量多聚体、ADAMTS13 活性和因子 VIII 的水平。此外，接受 BjV 与 Na2-EDTA 和/或 ABA 预孵育的大鼠的 VWF:Ag 水平往往恢复得更快。在小鼠中，BjV 导致 Vwf-/- 和 C57BL/6（背景对照）品系的血小板减少症，并且 VWF:Ag 水平在 C57BL/6 中趋于降低，表明血小板减少症与血浆 VWF 的存在无关。这些发现表明 BjV 中存在的 botrocetin 未能影响由毒液引起的血小板减少症的程度或时间过程，但它有助于降低血浆 VWF 的水平和功能。因此，在 B. jararaca 毒液过程中 VWF 的改变是一个附带事件，