The use of hydroxyurea and transfusion therapy is “strongly recommended” for patients with sickle cell disease, according to an evidence-based report by an expert panel of the National Heart, Lung, and Blood Institute.
The panel noted that when high-quality evidence was unavailable or insufficient — due to a limited number of randomized clinical trials conducted for sickle cell disease — panel consensus, as well as published, vetted guidelines from other organizations, was used to bolster its recommendations.
The revised management guidelines contain more than 500 specific directions providing guidance for all clinicians who care for patients with sickle cell disease, from primary care physicians to specialists that include hematologists. In addition, the report addresses a wide range of care, including treatment of acute complications, management of chronic complications and the use of disease-modifying therapies.
The recommendations were based on systematic review of available data collected from various medical databases, including Medline, Embase, Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, CINAHL, Toxline and Scopus. Pre-determined search terms were used to find randomized clinical trials, nonrandomized intervention studies and observational studies.
The quality of evidence and the strength of the recommendations were determined through a modification of the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system.
The panel determined that the use of hydroxyurea therapy is strongly recommended in the following patients:
- Any adult who has had three or more severe vasooclusive crises within a 1-year time frame;
- Patients with sickle cell disease pain or chronic, debilitating anemia;
- Patients with severe or chronic acute chest syndrome
Additionally, the panel issued a moderate-strength recommendation to offer hydroxyurea treatment, regardless of whether symptoms are present, to infants, children and adolescents.
The panel’s other strong recommendations included the following:
- Preventive measures: daily oral prophylactic penicillin in children up to age 5 years, annual transcranial Doppler exams in sickle cell anemia patients aged 2 to 16 years, and a long-term transfusion regimen to prevent stroke in those children with abnormal transcranial Doppler velocity.
- For acute complications: expeditious administration of opioid drugs to treat severe pain secondary to a vasoocclusive crisis, the use of an incentive spirometry deep breathing method in patients hospitalized for such an event.
- For chronic complications: combined treatment with analgesics and physical therapy for avascular necrosis, and treatment with ACE inhibitors for microalbuminuria in patients with sickle cell disease.
- For patients with proliferative sickle cell retinopathy: consultation with specialist to evaluate the possibility of laser photocoagulation, and for echocardiography to detect any signs of pulmonary hypertension.
“The expert panel realizes that this summary report and the guidelines leave many uncertainties for health professionals caring for individuals with [sickle cell disease] and highlight the importance of collaboration between primary care health professionals and [sickle cell disease] experts,” the researchers wrote. “However, we hope that this summary report and [sickle cell disease] 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.”
Linda J. Burns
Although the new sickle cell disease expert panel report has been endorsed by the American Society of Hematology, the society has acknowledged the gaps in evidence revealed by this analysis.
“There are a number of areas where there is clinical consensus; however, many recommendations are not based on strong evidence,” ASH President Linda J. Burns, MD, of the University of Minnesota, said in the press release. “This report is an important statement of what is known about how to care for our sickle cell patients. However, the gaps in evidence are striking and should be a call to redouble our efforts to continue our search for a cure and, in the meantime, provide the best possible care to patients with sickle cell disease.”
Disclosure: The panel members report no relevant financial disclosures.