title: Chronic transfusion therapy improves but does not normalize systemic and pulmonary vasculopathy in sickle cell disease.
abstract: Tricuspid regurgitant (TR) jet velocity and its relationship to pulmonary hypertension has been controversial in sickle cell disease (SCD). Plasma free hemoglobin is elevated in SCD patients and acutely impairs systemic vascular reactivity. We postulated that plasma free hemoglobin would be negatively associated with both systemic and pulmonary endothelial function, assessed by flow-mediated dilation (FMD) of the brachial artery and TR jet velocity, respectively. Whole blood viscosity, plasma free hemoglobin, TR jet, and FMD were measured in chronically transfused SCD pre- and posttransfusion (N = 25), in nontransfused SCD (N = 26), and in ethnicity-matched control subjects (N = 10). We found increased TR jet velocity and decreased FMD in nontransfused SCD patients compared with the other 2 groups. TR jet velocity was inversely correlated with FMD. There was a striking nonlinear relationship between plasma free hemoglobin and both TR jet velocity and FMD. A single transfusion in the chronically transfused cohort improved FMD. In our patient sample, TR jet velocity and FMD were most strongly associated with plasma free hemoglobin and transfusion status (transfusions being protective), and thus consistent with the hypothesis that intravascular hemolysis and increased endogenous erythropoiesis damage vascular endothelia.
authors.affiliation: Division of Cardiology, Children's Hospital Los Angeles, University of Southern California Keck School of Medicine, Los Angeles, CA; Department of Physiology and Biophysics, University of Southern California Keck School of Medicine, Los Angeles, CA;
authors.forename: Jon A
authors.identifier: http://orcid.org/0000-0002-2086-9569
authors.initials: JA
authors.lastname: Detterich
authors.affiliation: Division of Pediatric Pulmonology, Children's Hospital Los Angeles, Los Angeles, CA;
authors.forename: Roberta M
authors.initials: RM
authors.lastname: Kato
authors.affiliation: Department of Medicine, University of Pecs, Pecs, Hungary; and.
authors.forename: Miklos
authors.initials: M
authors.lastname: Rabai
authors.affiliation: Department of Physiology and Biophysics, University of Southern California Keck School of Medicine, Los Angeles, CA;
authors.forename: Herbert J
authors.initials: HJ
authors.lastname: Meiselman
authors.affiliation: Division of Hematology, Children's Hospital Los Angeles, University of Southern California Keck School of Medicine, Los Angeles, CA.
authors.forename: Thomas D
authors.initials: TD
authors.lastname: Coates
authors.affiliation: Division of Cardiology, Children's Hospital Los Angeles, University of Southern California Keck School of Medicine, Los Angeles, CA;
authors.forename: John C
authors.identifier: http://orcid.org/0000-0003-0996-3439
authors.initials: JC
authors.lastname: Wood
mesh_terms: D000293:Adolescent; D000328:Adult; D000755:Anemia, Sickle Cell / Q000097:blood / Q000000981:diagnostic imaging / Q000503:physiopathology* / Q000628:therapy; D001783:Blood Flow Velocity; D001803:Blood Transfusion; D001916:Brachial Artery / Q000000981:diagnostic imaging / Q000378:metabolism / Q000503:physiopathology*; D016022:Case-Control Studies; D004452:Echocardiography; D004730:Endothelium, Vascular / Q000000981:diagnostic imaging / Q000378:metabolism / Q000503:physiopathology; D005260:Female; D006321:Heart / Q000503:physiopathology; D006454:Hemoglobins / Q000378:metabolism; D006461:Hemolysis; D006801:Humans; D006976:Hypertension, Pulmonary / Q000097:blood / Q000000981:diagnostic imaging / Q000503:physiopathology*; D008168:Lung / Q000000981:diagnostic imaging / Q000378:metabolism / Q000503:physiopathology*; D008297:Male; D014262:Tricuspid Valve Insufficiency / Q000097:blood / Q000000981:diagnostic imaging / Q000503:physiopathology*; D014664:Vasodilation; D014783:Viscosity
chemical_list: D006454:Hemoglobins