Essential strategies and tactics for managing sickle cell disease

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doi:doi: 10.12788/jfp.0441

Applied Evidence

Essential strategies and tactics for managing sickle cell disease

J Fam Pract. 2022 July;71(6):254-261 | doi: 10.12788/jfp.0441

By

Robert Allen Perkins, MD, MPH

Ann Payne- Johnson, MD

Richelle Jefferson, MD

Key to patients’ well-being is the family physician’s watchfulness—through periodic lab testing and health checks and diligent application of preventive measures.

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PRACTICE RECOMMENDATIONS

› Offer rapid access to narcotic analgesia for patients with sickle cell disease (SCD) who have recurrent vaso-occlusive crises, to prevent unnecessary hospitalization. A

› Provide oral penicillin prophylaxis against pneumococcal disease in patients < 5 years of age who have sickle cell anemia (SCA), but not in children whose SCD is less severe. A

› Screen all patients with SCA annually, beginning at age 2 years until age 16 years, for their risk of stroke, using a transcranial Doppler study. A

› Administer the COVID-19 mRNA vaccine series to all patients with SCD, unless contraindicated. A

Strength of recommendation (SOR)

A Good-quality patient-oriented evidence
B Inconsistent or limited-quality patient-oriented evidence
C Consensus, usual practice, opinion, disease-oriented evidence, case series

References

1. Lubeck D, Agodoa I, Bhakta N, et al. Estimated life expectancy and income of patients with sickle cell disease compared with those without sickle cell disease. JAMA Netw Open. 2019;2:e1915374. doi:10.1001/jamanetworkopen.2019.15374

2. Swanson ME, Grosse SD, Kulkarni R. Disability among individuals with sickle cell disease: literature review from a public health perspective. Am J Prev Med. 2011;41(6 suppl 4):S390-S397. doi: 10.1016/j.amepre.2011.09.006

3. Moskowitz JT, Butensky E, Harmatz P, et al. Caregiving time in sickle cell disease: psychological effects in maternal caregivers. Pediatr Blood Cancer. 2007;48:64-71. doi:10.1002/pbc.20792

4. Mehta SR, Afenyi-Annan A, Lottenberg R. Opportunities to improve outcomes in sickle cell disease. Am Fam Phys. 2006;74:303-310.

5. Yawn BP, John-Sowah J. Management of sickle cell disease: recommendations from the 2014 Expert Panel Report. Am Fam Phys. 2015;92:1069-1077.

6. National Heart, Lung, and Blood Institute, National Institutes of Health. Evidence-based management of sickle cell disease. Expert Panel Report, 2014. Accessed June 9, 2022. www.nhlbi.nih.gov/health-pro/guidelines/sickle-cell-disease-guidelines

7. Committee Opinion No. 690: Carrier screening in the age of genomic medicine. Obstet Gynecol. 2017;129:e35-e40. doi: 10.1097/AOG.0000000000001951

8. Jordan LB, Smith-Whitley K, Treadwell MJ, et al. Screening U.S. college athletes for their sickle cell disease carrier status. Am J Prev Med. 2011;41:S406-S412. doi: 10.1016/j.amepre.2011.09.014

9. Adams RJ, McKie VC, Brambilla D, et al. Stroke prevention trial in sickle cell anemia. Control Clin Trials. 1998;19:110-129. doi: 10.1016/s0197-2456(97)00099-8

10. Alzahrani F, Alaidarous K, Alqarni S, et al. Incidence and predictors of bacterial infections in febrile children with sickle cell disease. Int J Pediatr Adolesc Med. 2021;8:236-238 doi: 10.1016/j.ijpam.2020.12.005

11. Committee on Infectious Diseases. Recommendations for prevention and control of influenza in children, 2021-2022. Pediatrics. 2021;148: e2021053745. doi: 10.1542/peds.2021-053745

12. Centers for Disease Control and Prevention. Study finds people with sickle cell disease who developed coronavirus disease have high rates of hospitalization, intensive care unit admission, and death. October 20, 2020. Accessed June 9, 2022. www.cdc.gov/ncbddd/sicklecell/features/scd-and-covid-19.html

13. James PA, Oparil S, Carter BL, et al. 2014 Evidence-based guideline for the management of high blood pressure in adults: report from the panel members appointed to the Eighth Joint National Committee (JNC 8). JAMA. 2014;311:507-520. doi:10.1001/jama.2013.284427

14. Baskin MN, Goh XL, Heeney MM, et al. Bacteremia risk and outpatient management of febrile patients with sickle cell disease. Pediatrics. 2013;131:1035-1041. doi: 10.1542/peds.2012-2139

15. Osunkwo I, Veeramreddy P, Arnall J, et al. Use of buprenorphine/naloxone in amelio rating acute care utilization and chronic opioid use in adults with sickle cell disease. Blood. 2019;134 (suppl 1):790. doi: 10.1182/blood-2019-126589

16. Vichinsky E, Hoppe CC, Ataga KI, et al; HOPE Trial Investigators. A phase 3 randomized trial of voxelotor in sickle cell disease. N Engl J Med. 2019;381:509-519. doi: 10.1056/NEJMoa1903212

17. Ataga KI, Kutlar A, Kanter J, et al. Crizanlizumab for the prevention of pain crises in sickle cell disease. N Engl J Med. 2017;376:429-439. doi: 10.1056/NEJMoa1611770

18. Dixit R, Nettem S, Madan SS, et al. Folate supplementation in people with sickle cell disease. Cochrane Database Syst Rev. 2016;2:CD011130. doi: 10.1002/14651858.CD011130.pub2

19. Brennan-Cook J, Bonnabeau E, Aponte R, et al. Barriers to care for persons with sickle cell disease: the case manager’s opportunity to improve patient outcomes. Prof Case Manag. 2018;23:213-219. doi: 10.1097/NCM.0000000000000260

The group of disorders known as sickle cell disease (SCD) is one of the more common genetic hemoglobinopathies. Homozygous production of the S variant of hemoglobin (Hb) in red blood cells (RBCs) results in profound sickling under conditions of physiologic stress, a condition known as Hb SS disease. People with Hb SS disease are at risk of chronic hemolytic anemia, tissue ischemia that causes vaso-occlusive pain syndrome, and other vaso-occlusive complications.¹ They also experience a > 20-year reduction in life expectancy, compared to age-matched controls; onset of risk of early death is usually after age 25 years.

People with heterozygous expression of the Hb S variant—that is, from one parent, and expression of Hb A from the other parent—are said to have sickle cell trait (SCT). They typically do not have symptoms of SCD, although they can experience vaso-occlusive pain under severe physiologic stress and suffer sudden death more often than age-matched controls. People who are heterozygous for Hb S but have another hemoglobinopathy (eg, sickle β⁰thalassemia) might have milder SCD, with fewer symptoms, or might have severe sickle cell anemia (SCA).

Alleviating the harsh burden of illness. All patients with SCD are more likely than age-matched counterparts to experience income loss because of their disability; the same loss is true for their caregivers. Such loss, when combined with time spent in the health care system, can be catastrophic.^2,3 But this loss can be mitigated with access to regular, comprehensive health care that includes the steps described here to detect SCD early and reduce the likelihood of complications.^4,5

To begin, TABLE 1⁶ lists typical laboratory findings and classifications in patients who are homozygous or heterozygous for Hb S, and therefore experience more severe Hb SS disease or milder SCD, respectively.

Who should be screened for hemoglobinopathy?

Because of the presence of the fetal Hb (Hb F) in newborns and infants, clinical signs of Hb SS before age 2 months are uncommon. Neonatal clinical laboratory testing is necessary for prompt identification of Hb SS; universal screening is now required by all states (although parents can opt out by claiming a religious exemption). A positive test result requires confirmatory testing: most often, Hb electrophoresis or DNA testing.

All patients with SCD are more likely than age-matched counterparts to experience income loss because of their disability. But this loss can be mitigated with access to regular, comprehensive health care.

A confirmed positive homozygous (Hb SS) or heterozygous (Hb S) result is reported to the patient’s identified medical home for subsequent management. Thus, pediatric patients with SCD can be identified, and prophylactic treatment initiated, as early as possible. Later in the patient’s life, repeat screening for SCD and SCT is recommended at the initiation of pregnancy care⁷ and prior to the start of high-intensity physical training, as occurs in college and professional athletics and in certain branches of the military.⁸

Putting prevention into practice

Some of the recommendations we make to prevent complications of SCD are directed only at patients with severe disease—ie, those who have Hb SS SCD or sickle β⁰ thalassemia (SCA); the rest apply to all patients with SCD (TABLE 2^6,9). (For patients with SCT, follow guidelines as you would for patients who do not have SCD, unless otherwise noted.)

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