TREATMENT OF SICKLE CELL DISEASE

Hydroxyurea and long-term, periodic blood transfusions should be used more often to treat patients with sickle cell disease (SCD), according to an expert panel.

In an article published in the September 10 issue of JAMA, the panel contends that both therapies are currently underused.

Cochairs Barbara P. Yawn, MD, MSPH, from the Olmsted Medical Center, Department of Research and Education, Rochester, Minnesota, and George R. Buchanan, MD, from the University of Texas Southwestern Medical Center in Dallas, led the panel in drafting a new guideline at the request of the National Heart, Lung, and Blood Institute.

The 12-member panel included experts in adult and pediatric hematology, family medicine, internal medicine, psychiatry, transfusion medicine, emergency nursing, and obstetrics and gynecology. They developed the guideline to support and expand the number of healthcare practitioners treating patients with SCD.

The relatively rare genetic disorder affects about 100,000 people in the United States, most of whom are black. People with SCD carry 2 copies of a mutated gene that makes sickle-shaped instead of disk-shaped hemoglobin. The sickle-shaped hemoglobin can slow blood flow and damage organs and can often cause severe body pain.

Hydroxyurea

The panel members write that hydroxyurea, a ribonucleotide reductase inhibitor, has been used since the 1970s to treat patients with myeloproliferative cancers, and since the 1980s, it has been used to treat patients with SCD. The drug is used to increase fetal hemoglobin levels. Short-term hydroxyurea therapy can result in a substantial reduction in the frequency of painful episodes and acute chest syndrome. Long-term therapy can result in reduced mortality.

"Hydroxyurea treatment of children beginning as early as 9 months of age yields improvements in laboratory parameters such as total hemoglobin and fetal hemoglobin levels and decreased numbers of sickle cell–related acute clinical events such as pain and [acute chest syndrome]," the panel writes. "The panel recommends that hydroxyurea therapy be offered in children beginning at 9 months of age, including those who are asymptomatic."

Blood Transfusions

The benefits of long-term transfusions vary, they write, but are generally associated with reduced risk for stroke in children. Possible complications include hyperviscosity and iron overload.

"Decisions to administer blood transfusions in persons with SCD must be based on risk-benefit assessments and are often made in consultation with a hematologist, transfusion medicine specialist, or SCD expert," the panel writes.

Overall

The guideline includes recommendations for health maintenance, including a strong recommendation for the administration of daily oral prophylactic penicillin up to the age of 5 years. The guideline also addresses acute and chronic complications including acute chest syndrome and pain. “Sickle cell pain often becomes chronic, resulting in poorer quality of life. Early and aggressive treatment of acute sickle cell pain may reduce the development of chronic pain,” the panel writes.

The panel's literature search turned up 12,532 references for initial review. The final analysis included 1575 original studies, and the panel also included evidence-based clinical practice guidelines as well as the expertise of panel members.

Still, overall, the literature lacks comprehensive evidence, the panel writes.

They conclude, "The process of developing guidelines for the management of children, adolescents, and adults with SCD has been challenging because high-quality evidence is limited in virtually every area related to SCD management.... The expert panel realizes that this summary report and the guidelines leave many uncertainties for health professionals caring for individuals with SCD and highlight the importance of collaboration between primary care health professionals and SCD experts. However, we hope that this summary report and the SCD guideline begins to facilitate improved and more accessible care for all affected individuals, and that the discrepancies in the existing data will trigger new research programs and processes to facilitate future guidelines."

The institutes sponsored this research and had a role in the design and conduct of the study, interpretation of the data, preparation of the manuscript, and decision to submit for publication. Panel members received no compensation for this work. Eight coauthors have reported receiving support, speaker or consulting fees, or serving on advisory boards from a number of companies or institutes. The remaining authors have disclosed no relevant financial relationships.

JAMA. 2014;312:1033-1048. Full text