Hemoglobin Mass and Blood Volume at Moderate Altitude: Establishing Lean-Body-Mass-Adjusted Reference Values for Clinical Use

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Background: Residing at high altitude is associated with increased red blood cell volume (RBCV) and reduced plasma volume (PV), changes that complicate interpretation of hemoglobin (Hb) and hematocrit (Hct). Here, we assess blood volume (BV), RBCV, PV, and hemoglobin mass (Hbmass) in individuals living at moderate altitude with the aim of deriving reference range for use in clinical practice. Methods: One hundred and fifty-eight moderate-altitude residents (ALT; 51 women) from Abha, Saudi Arabia (2250 m above sea level) were recruited and compared to 40 control subjects (CON; 0 women). Blood volumes and Hbmass were determined by carbon monoxide rebreathing. Lean body mass (LBM) was quantified by dual-energy X-ray absorptiometry and adjusted for. Results: When normalized to LBM, ALT men displayed an 8% increase in BV (109 vs 101 mL, p = 0.003), 14.8% increase in RBCV (54 vs 47 mL, p < 0.001), and 16.2% increase in Hbmass (18 vs 15 g, p < 0.001) compared to CON. ALT women exhibited lower BV (3928 vs 5476 mL), RBCV (1684 vs 2690 mL), PV (2276 vs 2767 mL), and Hbmass (558 vs 886 g), than ALT men, ( p < 0.001 for all). When expressed per body weight, ALT men have higher RBCV (33 vs 30 g), lower PV (34 vs 40 mL) and no different BV (68 vs 69 mL, p = 0.443). When expressed per LBM, gender differences in RBCV and Hbmass disappeared (RBCV: 54 vs 51 mL/kg LBM , p = 0.164; Hbmass: 18 vs 17 g/kg LBM , p = 0.201). Women have significantly higher BV (120 vs 109 mL/kg LBM ) owing to higher PV (72 vs 55 mL/kg LBM ). Conclusion: Moderate altitude is associated with a higher BV owing to a higher RBCV, which also explains the elevated Hb. A reference range based on the 5% and 97.5% percentiles of blood volumes and Hbmass adjusted for LBM is suggested for use in clinical practice. Keywords: hemoglobin, high altitude, red blood cell volume, carbon monoxide rebreathing, lean body mass, altitude

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