Kicken Cécile H, van der Vorm Lisa N, Zwaveling Suzanne, Schoenmaker Evi, Remijn Jasper A, Huskens Dana, de Laat Bas
Department of Anesthesiology, Maastricht University Medical Center, Maastricht, The Netherlands.
Synapse Research Institute, Maastricht, The Netherlands.
TH Open. 2019 Jul 22;3(3):e216-e226. doi: 10.1055/s-0039-1692991. eCollection 2019 Jul.
Although physical exercise is protective against cardiovascular disease, it can also provoke sudden cardiac death (exercise paradox). Epidemiological studies suggest that systemic hypoxia at high altitude is a risk factor for venous thromboembolism. Forthcoming, this study investigated the effect of repeated exercise at high altitude on blood coagulation, platelet function, and fibrinolysis. Six trained male volunteers were recruited. Participants ascended from sea level to 3,375 m altitude. They performed four exercise tests at 65 to 80% of their heart-rate reserve during 2 hours: one time at sea level and three times on consecutive days at 3,375 m altitude. Thrombin generation (TG) was measured in whole blood (WB) and platelet-rich and platelet-poor plasma. Coagulation factor levels were measured. Platelet activation was measured as αIIbβ3 activation and P-selectin expression. Fibrinolysis was studied using a clot-lysis assay. Normoxic exercise increased plasma peak TG through increased factor VIII (FVIII), and increased von Willebrand factor (VWF) and active VWF levels. Platelet granule release potential was slightly decreased. After repetitive hypoxic exercise, the increase in (active) VWF tapered, and there was no more distinct exercise-related increase in peak. Platelet aggregation potential and platelet-dependent TG decreased at high altitude. There were no effects on fibrinolysis upon exercise and/or hypoxia. Strenuous exercise induces a procoagulant state that is mediated by the endothelium, by increasing VWF and secondarily raising FVIII levels. After repetitive exercise, the amplitude of the endothelial response to exercise diminishes. A hypoxic environment appears to further attenuate the procoagulant changes by decreasing platelet activation and platelet-dependent TG.
尽管体育锻炼对心血管疾病具有保护作用，但它也可能引发心源性猝死（运动悖论）。流行病学研究表明，高海拔地区的全身性缺氧是静脉血栓栓塞的一个危险因素。本研究随即调查了在高海拔地区反复运动对血液凝固、血小板功能和纤维蛋白溶解的影响。
招募了六名受过训练的男性志愿者。参与者从海平面上升至海拔3375米处。他们在2小时内以心率储备的65%至80%进行了四次运动测试：一次在海平面，三次在海拔3375米处连续进行。在全血（WB）以及富血小板血浆和贫血小板血浆中测量凝血酶生成（TG）。测量凝血因子水平。通过αIIbβ3激活和P-选择素表达来测量血小板活化。使用凝块溶解试验研究纤维蛋白溶解。
常氧运动通过增加因子VIII（FVIII）、血管性血友病因子（VWF）和活性VWF水平，增加血浆TG峰值。血小板颗粒释放潜力略有下降。反复低氧运动后，（活性）VWF的增加逐渐减少，峰值不再有明显的与运动相关的增加。高海拔地区血小板聚集潜力和血小板依赖性TG降低。运动和/或低氧对纤维蛋白溶解没有影响。
剧烈运动通过增加VWF并继而提高FVIII水平，诱导由内皮介导的促凝状态。反复运动后，内皮对运动的反应幅度减小。缺氧环境似乎通过降低血小板活化和血小板依赖性TG，进一步减弱促凝变化。
