In lowlanders, high altitude (HA) acclimatization induces hemoconcentration by reducing plasma volume (PV) and increasing total hemoglobin mass (Hb). Conversely, Tibetan highlanders living at HA are reported to have a similar hemoglobin concentration ([Hb]) as lowlanders near sea level, and we investigated whether this reflects alterations in the PV or the Hb response to HA. Baseline assessment of PV and Hb was performed by carbon monoxide rebreathing at low altitudes (∼1,400 m) in Sherpas (an ethnic group of Tibetans living in Nepal) and native lowlanders. Participants then ascended to the Everest Base Camp (EBC) (5,400 m), where further measurements were performed after ∼2 days (EBC 1) and ∼6 wk (EBC 2). While on EBC 1 an increase in [Hb] was observed in lowlanders ( = 0.004) but not in Sherpas ( = 0.179), marked increases in [Hb] were observed in both groups on EBC 2 ( < 0.001). On EBC 1, Hb (Sherpas, = 0.393; lowlanders, = 0.123) and PV (Sherpas, = 0.348; lowlanders, = 0.172) were not different from baseline in either group, while circulating erythropoietin was increased in both groups ( < 0.001). On EBC 2, large increases in Hb and reductions in PV were observed along with elevated circulating erythropoietin in both groups (all < 0.002). Neither the increases in erythropoietin on EBC 1 ( = 0.846) or EBC 2 ( = 0.564) nor the expansion of Hb ( = 0.771) or reduction in PV ( = 0.099) on EBC 2 differed between the groups. We conclude that the hematological response of Sherpas to extended exposure to very high altitudes does not fundamentally differ from that of native lowlanders. We measured the hematological response to ∼6 wk exposure to an altitude of 5,400 m in Sherpa highland natives and Nepalese lowlanders. While the increase in hemoglobin concentration at high altitudes tended to be smaller in Sherpas than in lowlanders, the two groups experienced a similar reduction in plasma volume and increase in hemoglobin mass. We conclude that the hematological response of Sherpas to high-altitude exposure does not fundamentally differ from that of lowlanders.

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