Instituto Clodomiro Picado, Facultad de Microbiología, Universidad de Costa Rica, San José, Costa Rica.
Laboratorio de Hematología, Hospital Nacional de Niños 'Dr Carlos Sáenz Herrera', Caja Costarricense del Seguro Social, San José, Costa Rica.
PLoS Negl Trop Dis. 2024 Oct 2;18(10):e0012335. doi: 10.1371/journal.pntd.0012335. eCollection 2024 Oct.
The venom of Bothrops lanceolatus, a viperid species endemic to the Lesser Antillean Island of Martinique, induces thrombosis in a number of patients. Previous clinical observations indicate that thrombotic events are more common in patients bitten by juvenile specimens. There is a need to develop an experimental model of this effect in order to study the mechanisms involved.
METHODOLOGY/PRINCIPAL FINDINGS: The venoms of juvenile and adult specimens of B. lanceolatus were compared by (a) describing their proteome, (b) assessing their ability to induce thrombosis in a mouse model, and (c) evaluating their in vitro procoagulant activity and in vivo hemostasis alterations. Venom proteomes of juvenile and adult specimens were highly similar, albeit showing some differences. When injected by the intraperitoneal (i.p.) route, the venom of juvenile specimens induced the formation of abundant thrombi in the pulmonary vasculature, whereas this effect was less frequent in the case of adult venom. Thrombosis was not abrogated by the metalloproteinase inhibitor Batimastat. Both venoms showed a weak in vitro procoagulant effect on citrated mouse plasma and bovine fibrinogen. When administered intravenously (i.v.) venoms did not affect classical clotting tests (prothrombin time and activated partial thromboplastin time) but caused a partial drop in fibrinogen concentration. The venom of juvenile specimens induced partial alterations in some rotational thromboelastometry parameters after i.v. injection. When venoms were administered i.p., only minor alterations in classical clotting tests were observed with juvenile venom, and no changes occurred for either venom in rotational thromboelastometry parameters. Both juvenile and adult venoms induced a marked thrombocytopenia after i.p. injection.
CONCLUSIONS/SIGNIFICANCE: An experimental model of the thrombotic effect induced by B. lanceolatus venom was developed. This effect is more pronounced in the case of venom of juvenile specimens, despite the observation that juvenile and adult venom proteomes are similar. Adult and juvenile venoms do not induce a consumption coagulopathy characteristic of other Bothrops sp venoms. Both venoms induce a conspicuous thrombocytopenia. This experimental model reproduces the main clinical findings described in these envenomings and should be useful to understand the mechanisms of the thrombotic effect.
矛头蝮，一种小安的列斯群岛马提尼克岛特有的蝰蛇，其毒液会导致许多患者发生血栓。先前的临床观察表明，青少年标本咬伤的患者发生血栓性事件更为常见。为了研究相关机制，有必要建立这种效应的实验模型。
方法/主要发现：通过（a）描述其蛋白质组，（b）评估其在小鼠模型中诱导血栓形成的能力，以及（c）评估其体外促凝活性和体内止血改变，比较了幼年和成年矛头蝮的毒液。尽管存在一些差异，但幼年和成年标本的毒液蛋白质组非常相似。当通过腹腔（i.p.）途径注射时，幼年标本的毒液在肺血管中诱导形成大量血栓，而成年毒液的这种作用则不常见。金属蛋白酶抑制剂 Batimastat 并不能阻断血栓形成。两种毒液对柠檬酸化的小鼠血浆和牛纤维蛋白原均显示出微弱的体外促凝作用。静脉内（i.v.）给药时，毒液不会影响经典凝血测试（凝血酶原时间和激活部分凝血活酶时间），但会导致纤维蛋白原浓度部分下降。静脉内注射后，幼年毒液会引起一些旋转血栓弹性描记术参数的部分改变。当毒液腹腔内给药时，幼年毒液仅引起经典凝血测试的轻微改变，而两种毒液在旋转血栓弹性描记术参数方面均无变化。幼年和成年毒液腹腔内注射后均引起明显的血小板减少症。
结论/意义：建立了矛头蝮毒液诱导血栓形成的实验模型。尽管观察到幼年和成年毒液蛋白质组相似，但毒液的这种作用在幼年标本中更为明显。成年和幼年毒液不会引起其他矛头蝮毒液特有的消耗性凝血病。两种毒液均引起明显的血小板减少症。该实验模型再现了这些蛇咬伤中描述的主要临床发现，应该有助于理解血栓形成效应的机制。
