Assessment of hemoglobin mass and blood volumes at moderate altitude using carbon monoxide rebreathing method

At high altitudes, increased red blood cell volume (RBCV) and reduced plasma volume (PV) complicate interpretation of hemoglobin (Hb) and hematocrit (HCT) values. Whether moderate altitude affects these parameters remains debated. This study aimed to assess hemoglobin mass (Hb mass) and intravascular volumes at moderate altitude. Participants were recruited from a moderate-altitude population (2250 m above sea level) in the Aseer region, Saudi Arabia. Eligible individuals were healthy, with no medical conditions or prescribed medications. Participants with baseline Hb and HCT values outside the reference range were excluded. Hb mass, blood volume (BV), RBCV, and plasma volume (PV) were measured using the carbon monoxide (CO) rebreathing method. Body composition was assessed using dual-energy X-ray absorptiometry (DEXA). Results were reported as absolute values and normalized to body weight (BW) and lean body mass (LBM). Ninety-four participants (30 females, 64 males; mean age 25.8 ± 10.6 years) were included. Males had significantly higher absolute Hb mass (922.8 ± 195.0 vs 594.9 ± 91.2 g, P < .001), BV (5625.0 ± 1209.0 vs 4231.0 ± 881.0 mL, P < .001), PV (2903.0 ± 717.0 vs 2480.0 ± 552.0 mL, P = .005), and RBCV (2721.2 ± 56.9 vs 1749.8 ± 37.8 mL, P < .0001), as well as higher normalized Hb mass(BW) (11.7 ± 3.1 vs 9.9 ± 2.4 g/kgBW, P = .007) and RBCVBW (34.6 ± 8.8 vs 29.2 ± 7.1 mL/kg, P = .004). No gender differences were found in BV (P = .658) or PV (P = .155) when normalized to BW. Differences in Hb mass (P = .37) and RBCV (P = .39) also disappeared when normalized to LBM. However, females had higher BVLBM (126.8 ± 23.7 vs 110.9 ± 15.3 mL/kgLBM, P = .007) and PVLBM (75.0 ± 14.2 vs 56.6 ± 8.2 mL/kgLBM, P < .001). Compared to historical sea-level controls, altitude participants showed higher absolute Hb mass in males (P = .01) and females (P = .014), with higher values per LBM (P < .0001 for both). Hb and HCT showed significant but weak correlations with Hb mass and intravascular volumes. Residents at moderate altitudes have elevated Hb mass compared to sea-level references using the CO rebreathing technique. Population- and altitude-specific reference ranges for blood volumes and Hb mass CO rebreathing technique are needed for clinical application.