Lanetta Jordan

Management of Sickle Cell Disease: Summary of the 2014 Evidence-Based Report by Expert Panel Members

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.

Neuropsychological dysfunction and neuroimaging abnormalities in neurologically intact adults with sickle cell anemia

CONTEXT Sickle cell anemia (SCA) is a chronic illness causing progressive deterioration in quality of life. Brain dysfunction may be the most important and least studied problem affecting individuals with this disease. OBJECTIVE To measure neurocognitive dysfunction in neurologically asymptomatic adults with SCA vs healthy control individuals. DESIGN, SETTING, AND PARTICIPANTS Cross-sectional study comparing neuropsychological function and neuroimaging findings in neurologically asymptomatic adults with SCA and controls from 12 SCA centers, conducted between December 2004 and May 2008. Participants were patients with SCA (hemoglobin [Hb] SS and hemoglobin level < or = 10 mg/dL) aged 19 to 55 years and of African descent (n = 149) or community controls (Hb AA and normal hemoglobin level) (n = 47). Participants were stratified on age, sex, and education. MAIN OUTCOME MEASURES The primary outcome measure was nonverbal function assessed by the Wechsler Adult Intelligence Scale, third edition (WAIS-III) Performance IQ Index. Secondary exploratory outcomes included performance on neurocognitive tests of executive function, memory, attention, and language and magnetic resonance imaging measurement of total intracranial and hippocampal volume, cortical gray and white matter, and lacunae. RESULTS The mean WAIS-III Performance IQ score of patients with SCA was significantly lower than that of controls (adjusted mean, 86.69 for patients with SCA vs 95.19 for controls [mean difference, -5.50; 95% confidence interval {CI}, -9.55 to -1.44]; P = .008), with 33% performing more than 1 SD (<85) below the population mean. Among secondary measures, differences were observed in adjusted mean values for global cognitive function (full-scale IQ) (90.47 for patients with SCA vs 95.66 for controls [mean difference, -5.19; 95% CI, -9.24 to -1.13]; P = .01), working memory (90.75 vs 95.25 [mean difference, -4.50; 95% CI, -8.55 to -0.45]; P = .03), processing speed (86.50 vs 97.95 [mean difference, -11.46; 95% CI, -15.51 to -7.40]; P < .001), and measures of executive function. Anemia was associated with poorer neurocognitive function in older patients. No differences in total gray matter or hippocampal volume were observed. Lacunae were more frequent in patients with SCA but not independently related to neurocognitive function. CONCLUSION Compared with healthy controls, adults with SCA had poorer cognitive performance, which was associated with anemia and age.

Public health implications of sickle cell trait: a report of the CDC meeting.

Although the issue of whether sickle cell trait (SCT) is clinically benign or a significant health concern has not yet been resolved, the potential health risk to affected individuals is of vital importance and represents a tremendous challenge in protecting, promoting, and improving the health of the approximately 300 million people worldwide and 3 million people in the U.S. who possess the trait. In response to a request by the Sickle Cell Disease Association of America, in December 2009, the CDC convened a meeting of partners, stakeholders, and experts to identify the gaps in public health, clinical health services, epidemiologic research, and community-based outreach strategies and to develop an agenda for future initiatives. Through facilitated discussion and presentations in four topic areas, participants discussed pertinent issues, synthesized clinical research findings, and developed a coherent framework for establishing an agenda for future initiatives. A primary outcome of the meeting was to provide the first step of an iterative process to move toward agreement regarding appropriate counseling, care, and, potentially, treatment of people with SCT.

Renal medullary carcinoma and sickle cell trait: A systematic review

Sickle cell trait (SCT) carries a small risk of renal medullary carcinoma (RMC). We conducted a systematic literature review and reported new four RMC cases (total N = 217). Eighty eight percent had SCT and 8% had sickle cell disease; 50% were children. Males had 2.4× risk than females. Isolated hematuria or in combination with abdominal or flank pain was the presenting sign in 66% cases. Tumor‐related mortality was 95%. Four non‐metastatic patients were long‐term disease‐free survivors. Although risk appears to be very low, individuals with SCT should be informed about the low risk of RMC with the hope of early diagnosis. Hematuria should prompt immediate investigation. Pediatr Blood Cancer 2015;62:1694–1699.

Screening U.S. College Athletes for Their Sickle Cell Disease Carrier Status

There are many issues surrounding the screening of collegiate athletes for their sickle cell disease carrier status (or sickle cell trait), a genetic condition. This paper summarizes the establishment of expert advice given to the Secretarys Advisory Committee on Heritable Disorders in Newborns and Children (SACHDNC) on the issue. The SACHDNC has developed a report to advise the Secretary of the USDHHS about the 2010 rule of the National Collegiate Athletic Association (NCAA) requiring testing for sickle cell trait in all incoming Division I student athletes. The SACHDNC does not support the NCAAs rule to screen collegiate athletes for sickle cell trait.

Frequently asked questions by hospitalists managing pain in adults with sickle cell disease

Pain is the predominant medical presentation to hospitalists for patients with sickle cell disease (SCD). Dramatic treatment gains of SCD in childhood have resulted in more adults now requiring hospitalization than children. This has created new challenges to improve the quality of hospital care for SCD. The evidence base for pain management in SCD is lacking. We therefore offer some evidence and our informed opinion to answer frequently asked questions (FAQs) about pain management by hospitalists caring for adults with SCD. The most common questions center around defining a crisis; selecting and managing opioids; distinguishing between opioid tolerance, physical dependence, and addiction or misuse; determining appropriateness of discharge; and avoiding lengthy or recurrent hospitalizations.

Evidence gaps in the management of sickle cell disease: A summary of needed research.

An NHLBI expert panel recently published evidence-based guidelines for the care of people with sickle cell disease (SCD) [1]. The full report (http://www.nhlbi.nih.gov/health-pro/guidelines/sickle-cell-disease-guidelines/) was developed using a set of 30 important clinical questions raised by panel members. The systematic review of the literature, conducted through July 11, 2014, identified 22 randomized controlled trials specific to individuals with SCD. Some aspects of SCD management, e.g. stroke prevention in children and hydroxyurea use, had high quality evidence for specific recommendations. However, often the best available evidence was expert opinion, lower quality observational data, or adaptation of existing guidelines that did not specifically include people with SCD. When caring for individuals with rare diseases such as SCD, this level of evidence is frequently all that is available and thus forms the basis for the current standards of care, e.g. screening and referral decisions. The panel identified many shortcomings in the available evidence that are summarized in this article and reflect the panel’s opinions, expertise, and experience in all aspects of care for people with SCD. While mechanistic studies to improve understanding of SCD pathophysiology are critically needed to inform future clinical studies, a discussion of needed basic science research agendas was outside the scope of the panel’s mission. The domains for the many gaps correspond to the NHLBI guideline chapters on health maintenance, acute complications, chronic complications, and use of hydroxyurea and transfusion. Tables I and II summarize the evidence gaps in these areas.

Persistence and compliance of deferoxamine versus deferasirox in Medicaid patients with sickle-cell disease

What is known and Objective:  Patients with sickle‐cell disease (SCD) receiving chronic transfusions of red blood cells are at risk of developing serious adverse effects. Iron chelation therapy (ICT) helps eliminate iron overload by binding with plasma iron to form a non‐toxic conjugate that can be safely excreted from the body. Two iron chelating agents are currently available in the United States: Deferoxamine (DFO) is an injectable formulation, and deferasirox (Exjade®) is an oral suspension. This study compared the frequency of hospitalizations, persistence and compliance of patients with SCD from Medicaid programmes treated with DFO vs. deferasirox.

State-based surveillance for selected hemoglobinopathies

Purpose:The lack of an ongoing surveillance system for hemoglobinopathies in the United States impedes the ability of public health organizations to identify individuals with these conditions, monitor their health-care utilization and clinical outcomes, and understand the effect these conditions have on the health-care system. This article describes the results of a pilot program that supported the development of the infrastructure and data collection methods for a state-based surveillance system for selected hemoglobinopathies.Methods:The system was designed to identify and gather information on all people living with a hemoglobinopathy diagnosis (sickle cell diseases or thalassemias) in the participating states during 2004–2008. Novel, three-level case definitions were developed, and multiple data sets were used to collect information.Results:In total, 31,144 individuals who had a hemoglobinopathy diagnosis during the study period were identified in California; 39,633 in Florida; 20,815 in Georgia; 12,680 in Michigan; 34,853 in New York, and 8,696 in North Carolina.Conclusion:This approach provides a possible model for the development of state-based hemoglobinopathy surveillance systems.Genet Med 17 2, 125–130.

Multicenter COMPACT study of COMplications in Patients with sickle cell disease And utilization of iron Chelation Therapy

Abstract Background: Over the past few decades, lifespans of sickle cell disease (SCD) patients have increased; hence, they encounter multiple complications. Early detection, appropriate comprehensive care, and treatment may prevent or delay onset of complications. Objective: We collected longitudinal data on sickle cell disease (SCD) complication rates and associated resource utilization relative to blood transfusion patterns and iron chelation therapy (ICT) use in patients aged ≥16 years to address a gap in the literature. Research design and methods: Medical records of 254 SCD patients ≥16 years were retrospectively reviewed at three US tertiary care centers. Main outcome measures: We classified patients into cohorts based on cumulative units of blood transfused and ICT history: <15 units, no ICT (Cohort 1 [C1]), ≥15 units, no ICT (Cohort 2 [C2]), and ≥15 units with ICT (Cohort 3 [C3]). We report SCD complication rates per patient per year; cohort comparisons use rate ratios (RRs). Results: Cohorts had 69 (C1), 91 (C2), and 94 (C3) patients. Pain led to most hospitalizations (76%) and emergency department (ED) (82%) visits. Among transfused patients (C2+C3), those receiving ICT were less likely to experience SCD complications than those who did not (RR [95% CI] C2 vs. C3: 1.33 [1.25–1.42]). Similar trends (RR [95% CI]) were observed in ED visits and hospitalizations associated with SCD complications (C2 vs. C3, ED: 1.94 [1.70–2.21]; hospitalizations: 1.61 [1.45–1.78]), but not in outpatient visits. Conclusions: Although the most commonly reported SCD complication among all patients was pain, patients who received ICT were less likely to experience pain and other complications than those who did not. These results highlight the need for increased patient and provider education on the importance of comprehensive disease management.