Dense red blood cell and oxygen desaturation in sickle‐cell disease. Issue 10 (4th August 2016) - Di Liberto, Gaetana
Abstract : 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.