Subramanian Senthilkumaran, Ketan Patel, Elanchezhian Rajan, Pradeep Vijayakumar, Stephen W Miller, Alexandra Rucavado, Soheil Gilabadi, Medha Sonavane, Nicholas J Richards, Jarred Williams, Harry F Williams, Steven A Trim, Ponniah Thirumalaikolundusubramanian, José María Gutiérrez, Sakthivel Vaiyapuri
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For the first time, we report three serious cases of peripheral arterial thrombosis following Russell's viper bites and their diagnostic, clinical management, and mechanistic insights. These patients developed occlusive thrombi in their peripheral arteries and symptoms despite antivenom treatment. In addition to clinical features, computed tomography angiography was used to diagnose arterial thrombosis and ascertain its precise locations. They were treated using thrombectomy or amputation in one case that presented with gangrenous digits. Mechanistic insights into the pathology through investigations revealed the procoagulant actions of Russell's viper venom in standard clotting tests as well as in rotational thromboelastometry analysis. Notably, Russell's viper venom inhibited agonist-induced platelet activation. The procoagulant effects of Russell's viper venom were inhibited by a matrix metalloprotease inhibitor, marimastat, although a phospholipase A <sub>2</sub> inhibitor (varespladib) did not show any inhibitory effects. Russell's viper venom induced pulmonary thrombosis when injected intravenously in mice and thrombi in the microvasculature and affected skeletal muscle when administered locally. 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Although bleeding complications are frequently reported following viper envenomings, thrombotic events occur rarely (reported only in coronary and carotid arteries) with serious consequences. For the first time, we report three serious cases of peripheral arterial thrombosis following Russell's viper bites and their diagnostic, clinical management, and mechanistic insights. These patients developed occlusive thrombi in their peripheral arteries and symptoms despite antivenom treatment. In addition to clinical features, computed tomography angiography was used to diagnose arterial thrombosis and ascertain its precise locations. They were treated using thrombectomy or amputation in one case that presented with gangrenous digits. Mechanistic insights into the pathology through investigations revealed the procoagulant actions of Russell's viper venom in standard clotting tests as well as in rotational thromboelastometry analysis. 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引用次数: 0
摘要
罗素蝰(Daboia russelii)在印度和其他亚洲国家具有重要的医疗价值,它的毒液通常会导致出血、凝血病、坏死和急性肾损伤。虽然经常有毒蛇中毒后出血并发症的报道,但血栓事件却很少发生(仅有冠状动脉和颈动脉血栓事件的报道),而且后果严重。我们首次报告了三例被罗素蝰蛇咬伤后发生外周动脉血栓形成的严重病例,以及对这些病例的诊断、临床治疗和机理研究。这些患者尽管接受了抗蛇毒血清治疗,但外周动脉仍出现闭塞性血栓和症状。除临床特征外,还使用计算机断层扫描血管造影术诊断动脉血栓形成并确定其确切位置。他们接受了血栓切除术或截肢术治疗,其中一例出现了坏疽的手指。通过对病理机制的研究发现,在标准凝血试验和旋转血栓弹性测定分析中,罗素蝰毒液具有促凝血作用。值得注意的是,罗素蝰毒液能抑制激动剂诱导的血小板活化。基质金属蛋白酶抑制剂 marimastat 可抑制罗素蝰毒液的促凝血作用,但磷脂酶 A 2 抑制剂(varespladib)没有显示出任何抑制作用。小鼠静脉注射罗素蝰毒液会诱发肺血栓形成,局部注射则会在微血管中形成血栓并影响骨骼肌。这些数据强调了被蛇咬伤者外周动脉血栓形成的重要性,并为临床医生提供了解决这一问题的意识、机制和有力策略。
Peripheral Arterial Thrombosis following Russell's Viper Bites.
Envenomings by Russell's viper ( Daboia russelii ), a species of high medical importance in India and other Asian countries, commonly result in hemorrhage, coagulopathies, necrosis, and acute kidney injury. Although bleeding complications are frequently reported following viper envenomings, thrombotic events occur rarely (reported only in coronary and carotid arteries) with serious consequences. For the first time, we report three serious cases of peripheral arterial thrombosis following Russell's viper bites and their diagnostic, clinical management, and mechanistic insights. These patients developed occlusive thrombi in their peripheral arteries and symptoms despite antivenom treatment. In addition to clinical features, computed tomography angiography was used to diagnose arterial thrombosis and ascertain its precise locations. They were treated using thrombectomy or amputation in one case that presented with gangrenous digits. Mechanistic insights into the pathology through investigations revealed the procoagulant actions of Russell's viper venom in standard clotting tests as well as in rotational thromboelastometry analysis. Notably, Russell's viper venom inhibited agonist-induced platelet activation. The procoagulant effects of Russell's viper venom were inhibited by a matrix metalloprotease inhibitor, marimastat, although a phospholipase A 2 inhibitor (varespladib) did not show any inhibitory effects. Russell's viper venom induced pulmonary thrombosis when injected intravenously in mice and thrombi in the microvasculature and affected skeletal muscle when administered locally. These data emphasize the significance of peripheral arterial thrombosis in snakebite victims and provide awareness, mechanisms, and robust strategies for clinicians to tackle this issue in patients.