Nair Velu, Singh Surinderpal, Ashraf Mohammad Zahid, Yanamandra Uday, Sharma Vivek, Prabhakar Amit, Ahmad Rehan, Chatterjee Tathagata, Behera Vineet, Guleria Vivek, Patrikar Seema, Gupta Shivi, Vishnoi Madan Gopal, Kalshetty Kiran, Sharma Prafull, Bajaj Nitin, Khaling Thyelnai D, Wankhede Tanaji Sitaram, Bhattachar Srinivasa, Datta Rajat, Ganguli Late Prosenjit
Department of the Internal Medicine, Armed Forces Medical College, Pune, Maharashtra, India.
Director General Medical Services (Army), India.
Lancet Reg Health Southeast Asia. 2022 Jun 9;3:100016. doi: 10.1016/j.lansea.2022.05.005. eCollection 2022 Aug.
Previous literature suggests that thrombosis is more common in lowlanders sojourning at high altitude (HA) compared to near-sea-level. Though the pathophysiology is partly understood, little is known of its epidemiology. To elucidate this, an observational prospective longitudinal study was conducted in healthy soldiers sojourning for months at HA.
A total of 960 healthy male subjects were screened in the plains, of which 750 ascended, to altitudes above 15,000ft (4,472m). Clinical examination, haemogram, coagulogram, markers of inflammation and endothelial dysfunction, were studied at three time points during ascent and descent. The diagnosis of thrombosis was confirmed radiologically in all cases where a thrombotic event was suspected clinically. Subjects developing thrombosis at HA were labelled as Index Cases (ICs) and compared to a nested cohort of the healthy subjects (comparison group,(CG)) matched for altitude of stay.
Twelve and three subjects, developed venous (incidence: 5,926/10 person-years) and arterial (incidence: 1,482/10 person-years) thrombosis at HA, respectively. The ICs had enhanced coagulation (FVIIa: p<0.001; FXa: p<0.001) and decreased levels of natural anticoagulants (thrombomodulin, p=0.016; tissue factor pathway inhibitor [TFPI]: p<0.001) and a trend to dampened fibrinolysis (tissue plasminogen activator tPA; p=0.078) compared to CG. ICs also exhibited statistically significant increase in the levels of endothelial dysfunction and inflammation markers (vascular cell adhesion molecule-1[VCAM-1], intercellular adhesion molecule-1 [ICAM-1], vascular endothelial growth factor receptor 3 [VEGFR-3], P-Selectin, CD40 ligand, soluble C-reactive protein and myeloperoxidase: p<0.001).
The incidence of thrombosis in healthy subjects at HA was higher than that reported in literature at near sea-level. This was associated with inflammation, endothelial dysfunction, a prothrombotic state and dampened fibrinolysis.
Research grants from the Armed Forces Medical Research Committee, Office of the Director General of Armed Forces Medical Services (DGAFMS) & Defence Research and Development Organization (DRDO), Ministry of Defence, India.
既往文献表明，与海平面附近地区相比，在高海拔地区（HA）旅居的低地人血栓形成更为常见。尽管其病理生理学部分已为人所知，但其流行病学情况却知之甚少。为阐明这一点，我们对在高海拔地区旅居数月的健康士兵进行了一项前瞻性观察性纵向研究。
在平原地区共筛查了960名健康男性受试者，其中750人登上了海拔超过15000英尺（4472米）的高度。在上升和下降过程中的三个时间点对临床检查、血常规、凝血功能、炎症标志物和内皮功能障碍标志物进行了研究。在所有临床怀疑有血栓形成事件的病例中，均通过影像学检查确诊血栓形成。在高海拔地区发生血栓形成的受试者被标记为索引病例（ICs），并与一组在停留海拔高度上匹配的健康受试者（对照组，CG）进行比较。
在高海拔地区，分别有12名和3名受试者发生了静脉血栓形成（发病率：5926/10人年）和动脉血栓形成（发病率：1482/10人年）。与对照组相比，索引病例的凝血功能增强（FVIIa：p<0.001；FXa：p<0.001），天然抗凝剂水平降低（血栓调节蛋白，p=0.016；组织因子途径抑制剂[TFPI]：p<0.001），纤维蛋白溶解有减弱趋势（组织型纤溶酶原激活剂tPA；p=0.078）。索引病例的内皮功能障碍和炎症标志物水平也有统计学意义的升高（血管细胞黏附分子-1[VCAM-1]、细胞间黏附分子-1[ICAM-1]、血管内皮生长因子受体3[VEGFR-3]、P-选择素、CD40配体、可溶性C反应蛋白和髓过氧化物酶：p<0.001）。
高海拔地区健康受试者的血栓形成发生率高于文献报道的海平面附近地区。这与炎症、内皮功能障碍、血栓前状态和纤维蛋白溶解减弱有关。
印度国防部武装部队医学研究委员会、武装部队医疗服务总监办公室（DGAFMS）和国防研究与发展组织（DRDO）提供的研究资助。
