Integrative Vascular Biology Laboratory, Department of Integrative Physiology, University of Colorado, Boulder, Colorado, USA.
Centre for Heart, Lung and Vascular Health, Faculty of Health and Social Development, University of British Columbia Okanagan, Kelowna, British Columbia, Canada.
Exp Physiol. 2021 Jun;106(6):1335-1342. doi: 10.1113/EP089360. Epub 2021 Apr 27.
What is the central question of this study? Are coagulation and fibrinolytic factors disrupted in Andean highlanders with excessive erythrocytosis? What is the main finding and its importance? Excessive erythrocytosis is not associated with prothombotic disruptions in coagulation or the fibrinolytic system in Andean highlanders. Impairments in coagulation and fibrinolysis may not contribute to the increased vascular risk associated with excessive erythrocytosis.
Increased coagulation and reduced fibrinolysis are central factors underlying thrombotic risk and events. High altitude-induced excessive erythrocytosis (EE) is prevalent in Andean highlanders, contributing to increased cardiovascular risk. Disruption in the coagulation-fibrinolytic axis resulting in uncontrolled fibrin deposition might underlie the increased thrombotic risk associated with high-altitude EE. The experimental aim of this study was to determine whether EE is associated with a prothrombotic blood coagulation and fibrinolytic profile in Andean highlanders. Plasma coagulation factors (von Willebrand factor and factors VII, VIII and X), fibrinolytic factors [tissue-type plasminogen activator (t-PA) and plasminogen activator inhibitor-1 (PAI-1)] and D-dimer levels were determined in 26 male residents of Cerro de Pasco, Peru (4340 m a.s.l.): 12 without EE (age, 40 ± 13 years; haemoglobin, 17.4 ± 1.9 g/dl) and 14 with EE (age, 43 ± 15 years; haemoglobin, 24.4 ± 1.6 g/dl). There were no significant differences in von Willebrand factor (40.5 ± 24.8 vs. 45.5 ± 22.4%), factor VII (77.0 ± 14.5 vs. 72.5 ± 8.9%), factor VIII (55.6 ± 19.8 vs. 60.7 ± 26.8%) and factor X (73.9 ± 8.3 vs. 67.3 ± 10.9%) between the Andean highlanders without or with EE. The t-PA antigen (8.5 ± 3.6 vs. 9.6 ± 5.4 ng/ml), t-PA activity (5.5 ± 2.4 vs. 5.8 ± 1.6 IU/ml), PAI antigen (45.0 ± 33.8 vs. 40.5 ± 15.8 ng/ml), PAI-1 activity (0.24 ± 0.09 vs. 0.25 ± 0.11 IU/ml) and the molar concentration ratio of active t-PA to active PAI-1 (1:0.051 ± 0.034 vs. 1:0.046 ± 0.021 mmol/l) were also similar between the groups, as were D-dimer levels (235.0 ± 126.4 vs. 268.4 ± 173.7 ng/ml). Collectively, the results of the present study indicate that EE is not associated with a hypercoagulable, hypofibrinolytic state in Andean highlanders.
本研究的核心问题是什么?安第斯高地居民红细胞增多症是否会破坏凝血和纤维蛋白溶解因子?主要发现及其重要性是什么?红细胞增多症并不会引起安第斯高地居民凝血或纤维蛋白溶解系统的血栓前破坏。凝血和纤维蛋白溶解的损伤可能不会导致与红细胞增多症相关的血管风险增加。
凝血和纤维蛋白溶解的增加是血栓形成风险和事件的核心因素。由高海拔引起的红细胞增多症(EE)在安第斯高地居民中很常见,这增加了心血管风险。导致不可控纤维蛋白沉积的凝血-纤维蛋白溶解轴的破坏可能是与高海拔 EE 相关的血栓形成风险增加的基础。本研究的实验目的是确定 EE 是否与安第斯高地居民的促血栓形成的凝血和纤维蛋白溶解特征有关。在秘鲁塞罗德帕斯科的 26 名男性居民中(海拔 4340 米)确定了血浆凝血因子(血管性血友病因子和因子 VII、VIII 和 X)、纤维蛋白溶解因子[组织型纤溶酶原激活物(t-PA)和纤溶酶原激活物抑制剂-1(PAI-1)]和 D-二聚体水平:12 名无 EE(年龄 40±13 岁;血红蛋白 17.4±1.9 g/dl)和 14 名有 EE(年龄 43±15 岁;血红蛋白 24.4±1.6 g/dl)。无 EE 和有 EE 的安第斯高地居民的血管性血友病因子(40.5±24.8 vs. 45.5±22.4%)、因子 VII(77.0±14.5 vs. 72.5±8.9%)、因子 VIII(55.6±19.8 vs. 60.7±26.8%)和因子 X(73.9±8.3 vs. 67.3±10.9%)没有显著差异。t-PA 抗原(8.5±3.6 vs. 9.6±5.4 ng/ml)、t-PA 活性(5.5±2.4 vs. 5.8±1.6 IU/ml)、PAI 抗原(45.0±33.8 vs. 40.5±15.8 ng/ml)、PAI-1 活性(0.24±0.09 vs. 0.25±0.11 IU/ml)和活性 t-PA 与活性 PAI-1 的摩尔浓度比(1:0.051±0.034 vs. 1:0.046±0.021 mmol/l)在两组之间也相似,D-二聚体水平(235.0±126.4 vs. 268.4±173.7 ng/ml)也是如此。总之,本研究的结果表明,EE 与安第斯高地居民的高凝、低纤维蛋白溶解状态无关。