title: A systematic review of the literature for severity predictors in children with sickle cell anemia.
abstract: All patients with HbSS (SCA) share the same genetic mutation but the clinical phenotype is variable and difficult to predict early in life. A reliable severity predictor would be invaluable toward directing therapeutic decisions in those patients at highest risk of SCA complications. A search of PubMed, Cochrane Clinical Trials Register, and Scopus was performed to determine which SCA severity predictors have been validated in pediatric patients. The full text of 94 of the 590 references identified was reviewed based on the title/abstract. Fifty-four articles were included in the analysis. Alpha globin gene number was the most commonly studied severity predictor, followed by fetal hemoglobin (HbF) and reticulocyte count. Alpha thalassemia trait was protective against overt stroke and abnormal transcranial Doppler (TCD) in all but one study, but not frequency of painful crisis or silent cerebral infarct. Two thirds of the HbF studies reported beneficial effects with increasing HbF levels; however, increased HbF levels were not associated with lower hospitalization or stroke rates in others. The ability to predict SCA complications was mixed for all variables, except TCD and absolute reticulocyte count. More reliable predictors are urgently needed to guide therapeutic decisions in children with SCA.
authors.affiliation: Indiana Hemophilia and Thrombosis Center, Indianapolis, IN 46260, USA. Electronic address: emeier@ihtc.org.
authors.forename: Emily Riehm
authors.initials: ER
authors.lastname: Meier
authors.affiliation: Center for Transfusion and Cellular Therapies, Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA 30322, USA. Electronic address: ross.fasano@emory.edu.
authors.forename: Ross M
authors.initials: RM
authors.lastname: Fasano
authors.affiliation: Himmelfarb Health Sciences Library, The George Washington University School of Medicine and Health Sciences, Washington, DC 20037, USA. Electronic address: prlevett@gwu.edu.
authors.forename: Paul R
authors.initials: PR
authors.lastname: Levett
mesh_terms: D000755:Anemia, Sickle Cell / Q000097:blood / Q000175:diagnosis* / Q000235:genetics / Q000628:therapy; D015415:Biomarkers; D002648:Child; D005319:Fetal Hemoglobin; D006801:Humans; D011379:Prognosis; D017701:Reticulocyte Count; D012720:Severity of Illness Index; D055542:alpha-Globins / Q000378:metabolism; D055544:beta-Globins / Q000235:genetics / Q000378:metabolism
chemical_list: D015415:Biomarkers; D055542:alpha-Globins; D055544:beta-Globins; D005319:Fetal Hemoglobin
keywords: Alpha thalassemia; Fetal hemoglobin; Reticulocyte; Sickle cell anemia; Transcranial Doppler