Nielsen Vance G, Boyer Leslie V, Matika Ryan W, Amos Quinlan, Redford Daniel T
aDepartment of Anesthesiology bVIPER Institute, the University of Arizona College of Medicine, Tucson, Arizona, USA.
Blood Coagul Fibrinolysis. 2016 Jul;27(5):511-6. doi: 10.1097/MBC.0000000000000439.
In addition to degrading fibrinogen as a source of consumptive coagulopathy, rattlesnake venom has also been demonstrated to enhance fibrinolysis and degrade alpha-2-antiplasmin. The goals of this investigation was to characterize the kinetic fibrinolytic profile of Crotalus atrox venom in the absence and presence of tissue-type plasminogen activator (tPA), and to also ascertain if iron and carbon monoxide (CO, a positive modulator of alpha-2-antiplasmin) could attenuate venom-enhanced fibrinolysis. Utilizing thrombelastographic methods, the coagulation and fibrinolytic kinetic profiles of human plasma exposed to C. atrox venom (0-2 μg/ml) were determined in the absence or presence of tPA (0-100 IU/ml). Then, either separately or in combination, plasma was exposed to iron (ferric chloride, 10 μmol/l) or CO (carbon monoxide-releasing molecule-2, 100 μmol/l) prior to incubation with venom; the plasma sample was subsequently subjected to thrombelastographic analysis with addition of tPA. Venom exposure in the absence of tPA did not result in detectable fibrinolysis. In the presence of tPA, venom markedly enhanced fibrinolysis. Iron and CO, markedly attenuated venom enhancement of fibrinolysis. C. atrox venom enhances tPA-mediated fibrinolysis, and interventions that enhance/protect alpha-2-antiplasmin activity significantly attenuate venom-enhanced fibrinolysis. Future preclinical investigation is required to determine if iron and CO can attenuate venom-mediated degradation of alpha-2-antiplasmin-dependent fibrinolytic resistance.
除了降解纤维蛋白原作为消耗性凝血病的一个来源外，响尾蛇毒液还被证明可增强纤维蛋白溶解并降解α-2-抗纤溶酶。本研究的目的是表征在不存在和存在组织型纤溶酶原激活剂（tPA）的情况下，西部菱斑响尾蛇毒液的纤维蛋白溶解动力学特征，并确定铁和一氧化碳（CO，α-2-抗纤溶酶的正向调节剂）是否能减弱毒液增强的纤维蛋白溶解。利用血栓弹力图方法，在不存在或存在tPA（0-100 IU/ml）的情况下，测定暴露于西部菱斑响尾蛇毒液（0-2 μg/ml）的人血浆的凝血和纤维蛋白溶解动力学特征。然后，在与毒液孵育之前，血浆分别或联合暴露于铁（氯化铁，10 μmol/l）或CO（一氧化碳释放分子-2，100 μmol/l）；随后，在添加tPA的情况下，对血浆样本进行血栓弹力图分析。在不存在tPA的情况下暴露毒液未导致可检测到的纤维蛋白溶解。在存在tPA的情况下，毒液显著增强了纤维蛋白溶解。铁和CO显著减弱了毒液对纤维蛋白溶解增强作用。西部菱斑响尾蛇毒液增强了tPA介导的纤维蛋白溶解，而增强/保护α-2-抗纤溶酶活性的干预措施显著减弱了毒液增强的纤维蛋白溶解。需要未来的临床前研究来确定铁和CO是否能减弱毒液介导的对α-2-抗纤溶酶依赖性纤维蛋白溶解抵抗的降解。
