Department of Anesthesiology, The University of Arizona College of Medicine, Tucson, AZ 85724, USA.
Int J Mol Sci. 2024 Jun 7;25(12):6334. doi: 10.3390/ijms25126334.
Eastern Diamondback Rattlesnake () envenomation is a medical emergency encountered in the Southeastern United States. The venom contains a snake venom thrombin-like enzyme (SVTLE) that is defibrinogenating, causing coagulopathy without effects on platelets in humans. This investigation utilized thrombelastographic methods to document this coagulopathy kinetically on the molecular level in a rabbit model of envenomation via the analyses of whole blood samples without and with platelet inhibition. Subsequently, the administration of a novel ruthenium compound containing site-directed antivenom abrogated the coagulopathic effects of envenomation in whole blood without platelet inhibition and significantly diminished loss of coagulation in platelet-inhibited samples. This investigation provides coagulation kinetic insights into the molecular interactions and results of SVTLE on fibrinogen-dependent coagulation and confirmation of the efficacy of a ruthenium antivenom. These results serve as a rationale to investigate the coagulopathic effects of other venoms with this model and assess the efficacy of this site-directed antivenom.
东部菱斑响尾蛇(Eastern Diamondback Rattlesnake)毒液中毒是美国东南部遇到的一种医疗急症。毒液中含有一种蛇毒类凝血酶样酶(SVTLE),可导致纤维蛋白原降解,引起凝血功能障碍,而对人类血小板无影响。本研究利用血栓弹性图方法,通过分析无血小板抑制和有血小板抑制的全血样本,从分子水平上对兔模型中毒的这种凝血功能障碍进行动力学研究。随后,一种新型含钌化合物(含靶向抗蛇毒血清)的给药方案可消除无血小板抑制的全血中毒引起的凝血功能障碍,并显著减少血小板抑制样本中凝血的丧失。本研究为 SVTLE 对纤维蛋白原依赖性凝血的分子相互作用和结果提供了凝血动力学见解,并证实了钌抗蛇毒血清的疗效。这些结果为用该模型研究其他毒液的凝血功能障碍以及评估这种靶向抗蛇毒血清的疗效提供了依据。