Special Communication
September 10, 2014

Management of Sickle Cell DiseaseSummary of the 2014 Evidence-Based Report by Expert Panel Members

Author Affiliations
  • 1Olmsted Medical Center, Rochester, Minnesota
  • 2University of Texas Southwestern Medical Center, Dallas
  • 3University of North Carolina, Chapel Hill
  • 4Thomas Jefferson University, Cardeza Foundation, Philadelphia, Pennsylvania
  • 5University of Colorado, Denver
  • 6University of Virginia, Charlottesville
  • 7Foundation for Sickle Cell Disease Research, University of Miami, Miller School of Medicine, Miami, Florida
  • 8Johns Hopkins School of Medicine, Baltimore, Maryland
  • 9University of Florida, Gainesville
  • 10Brigham and Women’s Hospital and Harvard Medical School, Boston, Massachusetts
  • 11Duke University, Schools of Nursing and Medicine, Durham, North Carolina
  • 12Cincinnati Children’s Hospital Medical Center, Cincinatti, Ohio
  • 13Mayo Clinic College of Medicine, Rochester, Minnesota
  • 14National Heart, Lung, and Blood Institute, Bethesda, Maryland
  • 16Dr Goldsmith is now with the Rare Diseases Program, Office of New Drugs, US Food and Drug Administration, Bethesda, Maryland.
  • 17Dr Ortiz is now a private senior consultant in Bethesda, Maryland.
  • 18Dr Fulwood is now retired.
  • 15American Institutes for Research, Silver Spring, Maryland

Copyright 2014 American Medical Association. All Rights Reserved. Applicable FARS/DFARS Restrictions Apply to Government Use.

JAMA. 2014;312(10):1033-1048. doi:10.1001/jama.2014.10517

Importance  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.

Evidence Review  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.

Findings  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 and Relevance  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.