Amaru Ricardo, Prchal Josef, Ganz Tomas, Zhang Xu, Paton Daniela, Carrasco Mireya, Mancilla Emma, Gordeuk Victor R
Cell Biology Unit, School of Medicine, San Andres University, La Paz, Bolivia.
Instituto Boliviano de Oncohematologia, La Paz City, Bolivia.
J Hematol. 2025 Feb;14(1):20-25. doi: 10.14740/jh1388. Epub 2025 Jan 17.
Bolivian Andean Aymara highlanders, living at 4,000 m for 14,000 years, have evolved genetic adaptations to hypoxia. These include encoding prolyl hydroxylase 2 (PHD2), a regulator of transferrin transcription. Transferrin level increases in hypoxia and iron deficiency. Contrasting reports indicate that elevated transferrin is associated with experimentally induced thrombosis in mice undergoing short-stay at high altitude, but with decreased thrombosis in a congenital disorder of hypoxia-sensing.
A retrospective study was conducted in people living at high altitude (3,650 - 4,150 m). We analyzed serum transferrin concentration and thrombosis history in Aymara patients with high-altitude erythrocytosis (n = 149, median age 55 years, female gender 30%, iron deficiency 23%) or high-altitude anemia (n = 137, median age 43 years, female gender 86%, iron deficiency 57%).
The median transferrin concentration was 339 mg/dL in erythrocytosis patients versus 310 mg/dL in anemia patients (P = 0.037); it was 367 mg/dL in iron deficient versus 312 mg/dL in iron replete patients (P < 0.001). Thrombosis history was present in 13% of erythrocytosis and 8% of anemia patients (P = 0.25) and was present in 16% of iron deficient and 7% of iron replete patients (P = 0.017). After adjustment for erythrocytosis and iron deficiency in multivariate regression analysis, the mean (95% confidence interval) transferrin concentration was 277 (237 - 316) mg/dL in 30 patients with thrombosis history versus 324 (306 - 341) mg/dL in 256 patients without thrombosis history (P = 0.018). Similar trends occurred for the subgroups of arterial thrombosis history (P = 0.044) and venous thrombosis history (P = 0.22).
In individuals with extreme environmental hypoxia, we found no evidence that increased transferrin is associated with increased thrombosis history. Rather, we observed a trend to decreased thrombosis history with increased transferrin levels.
生活在海拔4000米达14000年之久的玻利维亚安第斯艾马拉高原居民已进化出对缺氧的遗传适应性。这些适应性包括编码脯氨酰羟化酶2（PHD2），它是转铁蛋白转录的调节因子。转铁蛋白水平在缺氧和缺铁时会升高。相互矛盾的报告表明，转铁蛋白升高与在高海拔短期停留的小鼠实验性诱导血栓形成有关，但在先天性缺氧感知障碍中与血栓形成减少有关。
对生活在高海拔地区（3650 - 4150米）的人群进行了一项回顾性研究。我们分析了患有高原红细胞增多症（n = 149，中位年龄55岁，女性占30%，缺铁占23%）或高原贫血（n = 137，中位年龄43岁，女性占86%，缺铁占57%）的艾马拉患者的血清转铁蛋白浓度和血栓形成史。
红细胞增多症患者的转铁蛋白浓度中位数为339mg/dL，而贫血患者为310mg/dL（P = 0.037）；缺铁患者为367mg/dL，铁充足患者为312mg/dL（P < 0.001）。血栓形成史在13%的红细胞增多症患者和8%的贫血患者中存在（P = 0.25），在16%的缺铁患者和7%的铁充足患者中存在（P = 0.017）。在多变量回归分析中对红细胞增多症和缺铁进行校正后，30例有血栓形成史的患者的平均（95%置信区间）转铁蛋白浓度为277（237 - 316）mg/dL，而256例无血栓形成史的患者为324（306 - 341）mg/dL（P = 0.018）。动脉血栓形成史亚组（P = 0.044）和静脉血栓形成史亚组（P = 0.22）也出现了类似趋势。
在极端环境缺氧的个体中，我们没有发现证据表明转铁蛋白升高与血栓形成史增加有关。相反，我们观察到随着转铁蛋白水平升高，血栓形成史有减少的趋势。
