Senthilkumaran Subramanian, Patel Ketan, Rajan Elanchezhian, Vijayakumar Pradeep, Miller Stephen W, Rucavado Alexandra, Gilabadi Soheil, Sonavane Medha, Richards Nicholas J, Williams Jarred, Williams Harry F, Trim Steven A, Thirumalaikolundusubramanian Ponniah, Gutiérrez José María, Vaiyapuri Sakthivel
Department of Emergency Medicine, Manian Medical Centre, Erode, Tamil Nadu, India.
School of Biological Sciences, University of Reading, Reading, United Kingdom.
TH Open. 2023 Jun 17;7(2):e168-e183. doi: 10.1055/s-0043-1769625. eCollection 2023 Apr.
Envenomings by Russell's viper ( ), 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 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.
在印度和其他亚洲国家，锯鳞蝰蛇（ ）是一种具有高度医学重要性的物种，其咬伤通常会导致出血、凝血功能障碍、坏死和急性肾损伤。虽然蝰蛇咬伤后经常报告出血并发症，但血栓形成事件很少发生（仅在冠状动脉和颈动脉中报告过），后果严重。我们首次报告了3例锯鳞蝰蛇咬伤后发生的严重外周动脉血栓形成病例，并对其诊断、临床管理及发病机制进行了深入分析。尽管接受了抗蛇毒血清治疗，这些患者的外周动脉仍形成了闭塞性血栓并出现了症状。除了临床特征外，计算机断层血管造影术还用于诊断动脉血栓形成并确定其确切位置。其中1例出现坏疽指的患者接受了血栓切除术或截肢治疗。通过研究对病理机制的深入分析表明，锯鳞蝰蛇毒在标准凝血试验以及旋转血栓弹力测定分析中均具有促凝血作用。值得注意的是，锯鳞蝰蛇毒可抑制激动剂诱导的血小板活化。基质金属蛋白酶抑制剂马立马司他可抑制锯鳞蝰蛇毒的促凝血作用，而磷脂酶A抑制剂（伐瑞普拉迪）则未显示出任何抑制作用。将锯鳞蝰蛇毒静脉注射到小鼠体内时会诱导肺血栓形成，局部给药时会导致微血管血栓形成并影响骨骼肌。这些数据强调了外周动脉血栓形成在蛇咬伤受害者中的重要性，并为临床医生处理此类患者的这一问题提供了认识、机制及有力的策略。
