The relationship between the severity of hemolysis, clinical manifestations and risk of death in 415 patients with sickle cell anemia in the US and Europe
Mehdi Nouraie,
Janet S. Lee,
Yingze Zhang,
Tamir Kanias,
Xuejun Zhao,
Zeyu Xiong,
Timothy B. Oriss,
Qilu Zeng,
Gregory J. Kato,
J. Simon R. Gibbs,
Mariana E. Hildesheim,
Vandana Sachdev,
Robyn J. Barst,
Roberto F. Machado,
Kathryn L. Hassell,
Jane A. Little,
Dean E. Schraufnagel,
Lakshmanan Krishnamurti,
Enrico Novelli,
Reda E. Girgis,
Claudia R. Morris,
Erika Berman Rosenzweig,
David B. Badesch,
Sophie Lanzkron,
Oswaldo L. Castro,
Jonathan C. Goldsmith,
Victor R. Gordeuk,
Mark T. Gladwin
Affiliations
Mehdi Nouraie
Howard University, Washington, USA
Janet S. Lee
Vascular Medicine Institute, University of Pittsburgh, USA;Division of Pulmonary, Allergy and Critical Care Medicine, University of Pittsburgh, USA
Yingze Zhang
Vascular Medicine Institute, University of Pittsburgh, USA
Tamir Kanias
Vascular Medicine Institute, University of Pittsburgh, USA;Division of Pulmonary, Allergy and Critical Care Medicine, University of Pittsburgh, USA
Xuejun Zhao
Cardiovascular and Pulmonary Medicine Branch, NHLBI, Bethesda, MD, USA
Zeyu Xiong
Vascular Medicine Institute, University of Pittsburgh, USA
Timothy B. Oriss
Division of Pulmonary, Allergy and Critical Care Medicine, University of Pittsburgh, USA
Qilu Zeng
Vascular Medicine Institute, University of Pittsburgh, USA
Gregory J. Kato
Cardiovascular and Pulmonary Medicine Branch, NHLBI, Bethesda, MD, USA
J. Simon R. Gibbs
National Heart & Lung Institute, Imperial College London, UK
Mariana E. Hildesheim
Division of Pulmonary, Allergy and Critical Care Medicine, University of Pittsburgh, USA
Vandana Sachdev
Cardiovascular and Pulmonary Medicine Branch, NHLBI, Bethesda, MD, USA
Robyn J. Barst
Columbia University, New York, USA
Roberto F. Machado
University of Illinois, Chicago, IL, USA
Kathryn L. Hassell
University of Colorado HSC, Denver, CO, USA
Jane A. Little
Case Western Reserve University, Cleveland, OH, USA
Dean E. Schraufnagel
University of Illinois, Chicago, IL, USA
Lakshmanan Krishnamurti
Children’s Hospital of Pittsburgh, Pittsburgh, PA, USA
Enrico Novelli
Vascular Medicine Institute, University of Pittsburgh, USA
Reda E. Girgis
Johns Hopkins University, Baltimore, MD, USA
Claudia R. Morris
Children’s Hospital & Research Center Oakland, Oakland, CA, USA
Erika Berman Rosenzweig
Columbia University, New York, USA
David B. Badesch
University of Colorado HSC, Denver, CO, USA
Sophie Lanzkron
Johns Hopkins University, Baltimore, MD, USA
Oswaldo L. Castro
Howard University, Washington, USA
Jonathan C. Goldsmith
National Heart Lung and Blood Institute/NIH, Bethesda, MD, USA
Victor R. Gordeuk
University of Illinois, Chicago, IL, USA
Mark T. Gladwin
Vascular Medicine Institute, University of Pittsburgh, USA;Division of Pulmonary, Allergy and Critical Care Medicine, University of Pittsburgh, USA
The intensity of hemolytic anemia has been proposed as an independent risk factor for the development of certain clinical complications of sickle cell disease, such as pulmonary hypertension, hypoxemia and cutaneous leg ulceration. A composite variable derived from several individual markers of hemolysis could facilitate studies of the underlying mechanisms of hemolysis. In this study, we assessed the association of hemolysis with outcomes in sickle cell anemia. A hemolytic component was calculated by principal component analysis from reticulocyte count, serum lactate dehydrogenase, aspartate aminotransferase and total bilirubin concentrations in 415 hemoglobin SS patients. Association of this component with direct markers of hemolysis and clinical outcomes was assessed. As primary validation, both plasma red blood cell microparticles and cell-free hemoglobin concentration were higher in the highest hemolytic component quartile compared to the lowest quartile (P≤0.0001 for both analyses). The hemolytic component was lower with hydroxyurea therapy, higher hemoglobin F, and alpha-thalassemia (P≤0.0005); it was higher with higher systemic pulse pressure, lower oxygen saturation, and greater values for tricuspid regurgitation velocity, left ventricular diastolic dimension and left ventricular mass (all P
