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About the Authors:
Emily Riehm Meier
Affiliations Molecular Medicine Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland, United States of America, Center for Cancer and Blood Disorders, Children’s National Medical Center, Washington, District of Columbia, United States of America, Department of Pediatrics, The George Washington University Medical Center, Washington, District of Columbia, United States of America
Colleen Byrnes
Affiliation: Molecular Medicine Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland, United States of America
Y. Terry Lee
Affiliation: Molecular Medicine Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland, United States of America
Elizabeth C. Wright
Affiliation: Office of the Director, National Institutes of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland, United States of America
Alan N. Schechter
Affiliation: Molecular Medicine Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland, United States of America
Naomi L. C. Luban
Affiliations Center for Cancer and Blood Disorders, Children’s National Medical Center, Washington, District of Columbia, United States of America, Department of Pediatrics, The George Washington University Medical Center, Washington, District of Columbia, United States of America
Jeffery L. Miller
* E-mail: [email protected]
Affiliation: Molecular Medicine Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland, United States of America
Introduction
Although the genetic basis of sickle cell anemia (HbSS, SCA) is well understood, the clinical phenotype is highly variable and difficult to predict. [1] Evidence of increased hemolysis begins during the first year of life as sickle hemoglobin (HbS) replaces fetal hemoglobin (HbF; α2γ2). With time, the consequences of intracellular HbS polymerization lead to susceptibility to infections, pain episodes, vascular and multi-organ damage, and shortened life expectancy. Splenic dysfunction affects over 90% of subjects before adulthood, [2] therefore antibiotic prophylaxis [3] is used during infancy to reduce the incidence of life threatening infection. [4] Patients are also treated with hydroxyurea (HU), chronic transfusions, and bone marrow transplantation, all of which have been shown to improve certain disease manifestations in children and adults. Monthly blood transfusions have decreased the stroke risk in SCA subpopulations. [5] However, because all...