Dense red blood cell and oxygen desaturation in sickle-cell disease

Am J Hematol. 2016 Oct;91(10):1008-13. doi: 10.1002/ajh.24467. Epub 2016 Aug 4.


Production of abnormal hemoglobin (HbS) in sickle-cell disease (SCD) results in its polymerization in deoxygenated conditions and in sickled-RBC formation. Dense RBCs (DRBCs), defined as density >1.11 and characterized by increased rigidity are absent in normal AA subjects, but present at percentages that vary of a patient to another remaining stable throughout adulthood for each patient. Polymerized HbS has reduced affinity for oxygen, demonstrated by the rightward shift of the oxygen-dissociation curve, leading to disturbances in oxygen transport. Ninety-two SCD patients' total RBCs were separated into LightDRBC (LRBC) (d < 1.11 g/mL) and DRBC fractions. Venous blood partial oxygen pressure and RBC-fraction-deoxygenation and -reoxygenation Hb-oxygen-equilibrium curves were determined. All patients took a 6-minute walking test (6MWT); 10 had results before and after >6 months on hydroxyurea. 6MWT time with SpO2 < 88% (TSpO2 < 88) assessed the physiological impact of exertion. Elevated mean corpuscular hemoglobin (Hb) concentrations, decreased %HbF, and 2,3-bisphosphoglycerates in DRBCs modulated Hb-oxygen affinity. Deoxygenation and reoxygenation Hb-oxygen equilibrium curves differed between normal Hb AA and SS RBCs and between LRBCs and DRBCs, with rightward shifts confirming HbS-polymerization's role in affinity loss. In bivariate analyses, 50% Hb saturation correlated positively with %DRBCs (P < 0.0001, r(2) = 0.34) and negatively with %HbF (P < 0.0001, r(2) = 0.25). The higher the %DRBCs, the longer the TSpO2 88 (P = 0.04). Hydroxyurea was associated with significantly shorter TSpO2 < 88 (P = 0.01). We report that the %DRBCs directly affects SCD patients' SpO2 during exertion; hydroxyurea improves oxygen affinity and lowers the %DRBCs. Am. J. Hematol. 91:1008-1013, 2016. © 2016 Wiley Periodicals, Inc.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 2,3-Diphosphoglycerate
  • Adult
  • Aged
  • Aged, 80 and over
  • Anemia, Sickle Cell / blood*
  • Anemia, Sickle Cell / physiopathology
  • Erythrocytes / metabolism*
  • Erythrocytes, Abnormal / metabolism
  • Erythrocytes, Abnormal / pathology
  • Female
  • Fetal Hemoglobin
  • Hemoglobin, Sickle
  • Humans
  • Hydroxyurea / pharmacology
  • Male
  • Middle Aged
  • Oxygen / blood*
  • Oxygen / metabolism
  • Physical Exertion
  • Polymerization
  • Prospective Studies
  • Young Adult


  • Hemoglobin, Sickle
  • 2,3-Diphosphoglycerate
  • Fetal Hemoglobin
  • Oxygen
  • Hydroxyurea