Erythropoietin Treatment at Sea Level Blunts the Altitude-induced Increase in Total Hemoglobin Mass

Introduction: Total hemoglobin mass (tHbmass) increases with high altitude (HA) acclimatization. However, it is unclear whether pharmacologically augmenting erythropoiesis with recombinant human erythropoietin (rEPO) at sea level prior to HA impacts the tHbmass response to HA acclimatization. PURPOSE: To determine the effect of rEPO compared to placebo (PL) on tHbmass during HA acclimatization. We hypothesize that tHbmass will be higher at sea level after receiving rEPO but will not be different between rEPO and PL after HA acclimatization. Methods: Venous blood was collected on 20 participants at baseline (sea level), during a 4-week sea level intervention (INT), and then on Days 1, 2, 7, and 14 at HA (Pikes Peak; 4300 m, 460 mmHg). After baseline samples were collected, participants received rEPO (Procrit; n=9; 2 F) or PL (saline; n=11; 3 F) for 4-weeks (50 IU/kg BW; 3x/week). Prior to HA ascent, all participants took acetazolamide for 3 ½ days (250 mg bid) with the last full dose taken on HA1. tHbmass was measured by CO-breathing before and after the INT (POSTINT), and the day after returning from HA (POSTHA). Arterial O 2 saturation (SaO 2 ) was estimated using pulse oximetry. Hematocrit, erythropoietin, and reticulocyte count (RETIC) were measured from blood samples. Statistical analyses were performed using linear mixed models with baseline values as a covariate. Results: As expected, rEPO augmented erythropoiesis at sea level. tHbmass was 88 g higher (p < 0.05) in the rEPO vs PL at POSTINT. Hematocrit was 6 percentage units higher in rEPO vs. PL upon arrival at altitude (HA1, p<0.05) and stayed 4 percentage units higher (on average) in the rEPO vs. PL throughout HA (HA2-14, p < 0.05). Despite similar SaO 2 between rEPO and PL at altitude (p > 0.05), erythropoietin was on average 7 mIU/mL lower in rEPO vs PL at HA1-7 (p < 0.05). Similarly, RETIC was 1 percentage unit lower (p < 0.05) in rEPO vs. PL at HA7 and HA14. tHbmass at POSTHA was not different between rEPO and PL (35 g, p > 0.05) which confirmed blunted erythropoiesis at HA. Conclusion: Pharmacological augmentation of erythropoiesis with rEPO at sea level blunted the increases in erythropoietin, RETIC, and tHbmass at HA. This is despite similar SaO 2 between rEPO and PL at HA. These novel findings provide unique insight into the regulation of erythropoiesis at altitude. Funded by USAMRDC: author views not representative of the U.S. Army or DoD. This abstract was presented at the American Physiology Summit 2025 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.