title: Management of sickle cell disease: summary of the 2014 evidence-based report by expert panel members.
abstract: OBJECTIVE
  Sickle cell disease (SCD) is a life-threatening genetic disorder affecting nearly 100,000 individuals in the United States and is associated with many acute and chronic complications requiring immediate medical attention. Two disease-modifying therapies, hydroxyurea and long-term blood transfusions, are available but underused.
  
  
  OBJECTIVE
  To support and expand the number of health professionals able and willing to provide care for persons with SCD.
  
  
  METHODS
  Databases of MEDLINE (including in-process and other nonindexed citations), EMBASE, Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, CINAHL, TOXLINE, and Scopus were searched using prespecified search terms and keywords to identify randomized clinical trials, nonrandomized intervention studies, and observational studies. Literature searches of English-language publications from 1980 with updates through April 1, 2014, addressed key questions developed by the expert panel members and methodologists.
  
  
  RESULTS
  Strong recommendations for preventive services include daily oral prophylactic penicillin up to the age of 5 years, annual transcranial Doppler examinations from the ages of 2 to 16 years in those with sickle cell anemia, and long-term transfusion therapy to prevent stroke in those children with abnormal transcranial Doppler velocity (≥200 cm/s). Strong recommendations addressing acute complications include rapid initiation of opioids for treatment of severe pain associated with a vasoocclusive crisis, and use of incentive spirometry in patients hospitalized for a vasoocclusive crisis. Strong recommendations for chronic complications include use of analgesics and physical therapy for treatment of avascular necrosis, and use of angiotensin-converting enzyme inhibitor therapy for microalbuminuria in adults with SCD. Strong recommendations for children and adults with proliferative sickle cell retinopathy include referral to expert specialists for consideration of laser photocoagulation and for echocardiography to evaluate signs of pulmonary hypertension. Hydroxyurea therapy is strongly recommended for adults with 3 or more severe vasoocclusive crises during any 12-month period, with SCD pain or chronic anemia interfering with daily activities, or with severe or recurrent episodes of acute chest syndrome. A recommendation of moderate strength suggests offering treatment with hydroxyurea without regard to the presence of symptoms for infants, children, and adolescents. In persons with sickle cell anemia, preoperative transfusion therapy to increase hemoglobin levels to 10 g/dL is strongly recommended with a moderate strength recommendation to maintain sickle hemoglobin levels of less than 30% prior to the next transfusion during long-term transfusion therapy. A strong recommendation to assess iron overload is accompanied by a moderate strength recommendation to begin iron chelation therapy when indicated.
  
  
  CONCLUSIONS
  Hydroxyurea and transfusion therapy are strongly recommended for many individuals with SCD. Many other recommendations are based on quality of evidence that is less than high due to the paucity of clinical trials regarding screening, management, and monitoring for individuals with SCD.
authors.affiliation: Olmsted Medical Center, Rochester, Minnesota.
authors.forename: Barbara P
authors.initials: BP
authors.lastname: Yawn
authors.affiliation: University of Texas Southwestern Medical Center, Dallas.
authors.forename: George R
authors.initials: GR
authors.lastname: Buchanan
authors.affiliation: University of North Carolina, Chapel Hill.
authors.forename: Araba N
authors.initials: AN
authors.lastname: Afenyi-Annan
authors.affiliation: Thomas Jefferson University, Cardeza Foundation, Philadelphia, Pennsylvania.
authors.forename: Samir K
authors.initials: SK
authors.lastname: Ballas
authors.affiliation: University of Colorado, Denver.
authors.forename: Kathryn L
authors.initials: KL
authors.lastname: Hassell
authors.affiliation: University of Virginia, Charlottesville.
authors.forename: Andra H
authors.initials: AH
authors.lastname: James
authors.affiliation: Foundation for Sickle Cell Disease Research, University of Miami, Miller School of Medicine, Miami, Florida.
authors.forename: Lanetta
authors.initials: L
authors.lastname: Jordan
authors.affiliation: Johns Hopkins School of Medicine, Baltimore, Maryland.
authors.forename: Sophie M
authors.initials: SM
authors.lastname: Lanzkron
authors.affiliation: University of Florida, Gainesville.
authors.forename: Richard
authors.initials: R
authors.lastname: Lottenberg
authors.affiliation: Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts.
authors.forename: William J
authors.initials: WJ
authors.lastname: Savage
authors.affiliation: Duke University, Schools of Nursing and Medicine, Durham, North Carolina.
authors.forename: Paula J
authors.initials: PJ
authors.lastname: Tanabe
authors.affiliation: Cincinnati Children's Hospital Medical Center, Cincinatti, Ohio.
authors.forename: Russell E
authors.initials: RE
authors.lastname: Ware
authors.affiliation: Mayo Clinic College of Medicine, Rochester, Minnesota.
authors.forename: M Hassan
authors.initials: MH
authors.lastname: Murad
authors.affiliation: National Heart, Lung, and Blood Institute, Bethesda, Maryland16Dr Goldsmith is now with the Rare Diseases Program, Office of New Drugs, US Food and Drug Administration, Bethesda, Maryland.
authors.forename: Jonathan C
authors.initials: JC
authors.lastname: Goldsmith
authors.affiliation: National Heart, Lung, and Blood Institute, Bethesda, Maryland17Dr Ortiz is now a private senior consultant in Bethesda, Maryland.
authors.forename: Eduardo
authors.initials: E
authors.lastname: Ortiz
authors.affiliation: National Heart, Lung, and Blood Institute, Bethesda, Maryland18Dr Fulwood is now retired.
authors.forename: Robinson
authors.initials: R
authors.lastname: Fulwood
authors.affiliation: American Institutes for Research, Silver Spring, Maryland.
authors.forename: Ann
authors.initials: A
authors.lastname: Horton
authors.affiliation: National Heart, Lung, and Blood Institute, Bethesda, Maryland.
authors.forename: Joylene
authors.initials: J
authors.lastname: John-Sowah
mesh_terms: D000293:Adolescent; D000328:Adult; D000701:Analgesics, Opioid / Q000627:therapeutic use; D000755:Anemia, Sickle Cell / Q000628:therapy*; D019072:Antibiotic Prophylaxis; D001803:Blood Transfusion; D002648:Child; D002675:Child, Preschool; D003245:Consensus Statements as Topic; D019317:Evidence-Based Medicine; D006801:Humans; D006918:Hydroxyurea / Q000627:therapeutic use*; D007223:Infant; D010406:Penicillins / Q000627:therapeutic use; D026741:Physical Therapy Modalities
chemical_list: D000701:Analgesics, Opioid; D010406:Penicillins; D006918:Hydroxyurea