title: Dense red blood cell and oxygen desaturation in sickle-cell disease.
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.
authors.affiliation: INSERM-U955, Equipe 2: Transfusion Et Maladies Du Globule Rouge, Laboratoire D'Excellence, GRex, Institut Mondor, Créteil, France.|Etablissement Français Du Sang, Île-de-France Mondor, Créteil, France.
authors.forename: Gaetana
authors.initials: G
authors.lastname: Di Liberto
authors.affiliation: INSERM-U955, Equipe 2: Transfusion Et Maladies Du Globule Rouge, Laboratoire D'Excellence, GRex, Institut Mondor, Créteil, France.
authors.forename: Laurent
authors.initials: L
authors.lastname: Kiger
authors.affiliation: INSERM-U955, Equipe 2: Transfusion Et Maladies Du Globule Rouge, Laboratoire D'Excellence, GRex, Institut Mondor, Créteil, France.
authors.forename: Michael C
authors.initials: MC
authors.lastname: Marden
authors.affiliation: INSERM, Unité U955, Equipe 4: Physiopathologie De La Bronchopneumopathie Chronique Obstructive Et Autres Conséquences Respiratoires De L'inhalation De Particules De L'environnement, Créteil, France.
authors.forename: Laurent
authors.initials: L
authors.lastname: Boyer
authors.affiliation: Pôle Recherche Clinique - Santé Publique, Hôpital Henri-Mondor, and Laboratoire D'Investigation Clinique: Epidémiologie Clinique - Evaluation Médico-Economique, LIC EA 4393, Université Paris-Est Créteil, Créteil, 94010, France.
authors.forename: Florence Canoui
authors.initials: FC
authors.lastname: Poitrine
authors.affiliation: Service De Biochimie, Hôpital Henri-Mondor, AP-HP, Université Paris-Est, Créteil, 94010, France.
authors.forename: Marc
authors.initials: M
authors.lastname: Conti
authors.affiliation: INSERM-U955, Equipe 2: Transfusion Et Maladies Du Globule Rouge, Laboratoire D'Excellence, GRex, Institut Mondor, Créteil, France.
authors.forename: Marie Georgine
authors.initials: MG
authors.lastname: Rakotoson
authors.affiliation: Centre De Référence Des Syndromes Drépanocytaires Majeurs, Hôpital Henri-Mondor, Assistance Publique-Hôpitaux De Paris (AP-HP), Université Paris-Est Créteil, Créteil, France.
authors.forename: Anoosha
authors.initials: A
authors.lastname: Habibi
authors.affiliation: Etablissement Français Du Sang, Île-de-France Mondor, Créteil, France.
authors.forename: Sanam
authors.initials: S
authors.lastname: Khorgami
authors.affiliation: Etablissement Français Du Sang, Île-de-France Mondor, Créteil, France.
authors.forename: Benoit
authors.initials: B
authors.lastname: Vingert
authors.affiliation: Service De Réanimation Médicale, Hôpital Henri-Mondor, AP-HP, Université Paris-Est, Créteil, France.
authors.forename: Bernard
authors.initials: B
authors.lastname: Maitre
authors.affiliation: INSERM-U955, Equipe 2: Transfusion Et Maladies Du Globule Rouge, Laboratoire D'Excellence, GRex, Institut Mondor, Créteil, France.|Centre De Référence Des Syndromes Drépanocytaires Majeurs, Hôpital Henri-Mondor, Assistance Publique-Hôpitaux De Paris (AP-HP), Université Paris-Est Créteil, Créteil, France.
authors.forename: Frederic
authors.initials: F
authors.lastname: Galacteros
authors.affiliation: INSERM-U955, Equipe 2: Transfusion Et Maladies Du Globule Rouge, Laboratoire D'Excellence, GRex, Institut Mondor, Créteil, France.|Etablissement Français Du Sang, Île-de-France Mondor, Créteil, France.
authors.forename: France
authors.initials: F
authors.lastname: Pirenne
authors.affiliation: INSERM-U955, Equipe 2: Transfusion Et Maladies Du Globule Rouge, Laboratoire D'Excellence, GRex, Institut Mondor, Créteil, France. pablo.bartolucci@aphp.fr.|Centre De Référence Des Syndromes Drépanocytaires Majeurs, Hôpital Henri-Mondor, Assistance Publique-Hôpitaux De Paris (AP-HP), Université Paris-Est Créteil, Créteil, France. pablo.bartolucci@aphp.fr.
authors.forename: Pablo
authors.initials: P
authors.lastname: Bartolucci
mesh_terms: D019794:2,3-Diphosphoglycerate; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000755:Anemia, Sickle Cell / Q000097:blood* / Q000503:physiopathology; D004912:Erythrocytes / Q000378:metabolism*; D004913:Erythrocytes, Abnormal / Q000378:metabolism / Q000473:pathology; D005260:Female; D005319:Fetal Hemoglobin; D006451:Hemoglobin, Sickle; D006801:Humans; D006918:Hydroxyurea / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D010100:Oxygen / Q000097:blood* / Q000378:metabolism; D005082:Physical Exertion; D058105:Polymerization; D011446:Prospective Studies; D055815:Young Adult
chemical_list: D006451:Hemoglobin, Sickle; D019794:2,3-Diphosphoglycerate; D005319:Fetal Hemoglobin; D010100:Oxygen; D006918:Hydroxyurea