September 16, 2020

General Management Strategies for Patients With Sickle Cell Disease

A primary care update

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By Seth Rotz, MD

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*Please note: This is an abridged version of an article that originally appeared in the Cleveland Clinic Journal of Medicine. For the complete article please visit: https://www.ccjm.org/content/87/1/19.

Approximately 100,000 people live with sickle cell disease (SCD) in the United States, and 1 of every 350 black children is born with the disease.1 Advances in health maintenance and therapy mean that more young patients are surviving to adulthood, requiring care in the adult primary care setting.

While the survival rate has improved for adults with SCD, their life expectancy is still more than two decades shorter than in the general population, as complications of chronic SCD interact with age-related non-SCD conditions and add to the disease morbidity.2–5 An alliance of patient, primary care physician, hematologist and other caregivers is crucial to optimizing disease outcomes, and the primary care physician is an important partner in providing optimal care of these patients. Here, we review mechanisms of sickle cell disease, common complications and their management based on current guidelines, and current approaches to health maintenance.

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General management strategies

Current management strategies include prophylactic penicillin and immunizations to decrease the occurrence of pneumococcal infections, hydroxyurea (a disease-modifying agent), blood transfusions (for symptomatic acute anemia, stroke management, preoperative optimization) and bone marrow transplant.

In 2017, the US Food and Drug Administration (FDA) approved L-glutamine oral powder for reducing acute complications of SCD, and many other drugs are in development and undergoing clinical testing. Gene therapy is also progressing, with a recently reported successful outcome in one patient.7

The National Heart, Lung and Blood Institute (NHLBI) has developed guidelines for the care of SCD patients; the most recent version was published in 2014.8 The American Society of Hematology has developed new guidelines on the management of SCD complications, which are available here.

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  • The medical home model of care. Establishing a medical home—comprehensive care based on a partnership between the patient, family, primary care physician and other medical staff—is of paramount importance to the care of the SCD patient. Typically, care is provided by a hematologist in collaboration with the primary care physician. In some instances, a single setting is used, such as a comprehensive sickle cell clinic. Often, a primary care physician knowledgeable in the care of SCD functions as the sole provider. Referral to subspecialists is used as needed to manage disease complications.
  • Regular medical evaluations. Regular medical evaluations are essential in assessing disease severity and progression. A detailed history and physical examination enable the clinician to note deviations from the previous clinical status and to identify new stressors. The regular visit is also an opportunity to address chronic complications, as discussed in the following sections. Efforts should be made to perform a yearly comprehensive review to screen for chronic complications of SCD and to facilitate specialty referrals.
  • Immunization. Immunization status should be reviewed to ensure compliance with vaccinations.
  • Albuminemia. Microalbuminemia screening is done through urinalysis and is confirmed with an albumincreatinine ratio. For micro- or macroalbuminuria with no other known cause, the NHLBI guidelines recommend angiotensin-converting enzyme (ACE) inhibitor therapy. Since the standard calculations of glomerular filtration rate cannot be used reliably in patients with SCD and in the acute setting, an increase in creatinine of 0.3 mg/dL should prompt an avoidance of nephrotoxic agents.
  • Enuresis. Enuresis secondary to hyposthenuria (dilute urine) can occur, exacerbating dehydration. Adult patients may not wish to divulge this information voluntarily.
  • Pulmonary hypertension. Pulmonary hypertension and acute chest syndrome are major causes of death in SCD. Guidelines for screening in SCD patients by the American College of Chest Physicians and the Pulmonary Hypertension Association recommend echocardiography or testing for plasma N-terminal pro-brain natriuretic peptide. However, the frequency of screening has not been established.26
  • Osteopenia. Osteopenia with or without osteoporosis, defined by decreased bone mineral density, has been reported in up to 80% of adults with SCD. Significant vitamin D deficiency was associated with a higher prevalence of fracture history, secondary hyperparathyroidism and increased bone turnover.27 Studies have shown the potential benefit of vitamin D in reducing the number of pain days in SCD.27,28
  • Avascular necrosis. Avascular necrosis can reduce the ability to perform activities of daily living. Though there is no standardized approach to prevention or therapy, early involvement of a physical therapist and orthopedic specialist can improve function and help assess the need for surgical intervention.
  • Antibiotic prophylaxis. It has been recommended that patients with SCD who have a history of splenectomy or an invasive pneumococcal infection be placed on indefinite prophylaxis with penicillin.8
  • Chronic pain syndrome. Chronic pain syndrome is described as pain that persists for at least three months. It is usually described as pain that is deep, nagging, achy and constant.29 Neuropathic pain resulting from peripheral or central nervous system dysfunction manifests as allodynia and hyperalgesia.29 Opioids are the mainstay of SCD pain management and may be used in conjunction with nonpharmacologic interventions. Clinicians need to be wary of stigmatizing these patients as drug-seekers, as this can result in delayed treatment and undertreatment. A doctor-patient relationship based on respect and trust will optimize pain management in these patients, and establishing this type of relationship should be a priority, as well as more frequent monitoring of disease status. While detailed management of chronic pain and pain crises in SCD is beyond the scope of this article, it should be noted that individualized pain management plans crafted with the participation of the patient or caregiver may help facilitate adherence. Concerns about drug-seeking behavior should be addressed after treatment of acute episodes. Effects of chronic opioid use (tolerance, dependence, and addiction) occur, and the provider may need to involve a pain management expert for collaboration in patient care.
  • Neurocognitive effects of sickle cell disease. Neurocognitive dysfunction should be assessed with a focused history (memory deficits, work/school challenges, difficulties with medication adherence), followed by neuropsychiatric evaluation as appropriate. Vichinsky et al30 reported that adult patients with SCD who did not have neurologic symptoms remained at risk for neurocognitive performance deficits; their anemia may induce neurocognitive impairment secondary to cerebral hypoxemia undetected on standard neuroimaging. Early identification of patients with difficulties on specific measures of neurocognitive function may encourage earlier enrollment in cognitive rehabilitation programs.30
  • Reproductive health. The regular evaluation should include discussion of fertility, contraception, erectile dysfunction and available treatment options. Before conception, genetic counseling should be offered to address modes of disease inheritance and transmission, as well as options for preimplantation genetic diagnosis. Pregnancy in SCD patients is a high-risk condition and warrants care from a team of specialists including a perinatologist, adult hematologist and specialists involved in the management of SCD-related complications.
  • Medication adherence. Adherence to medications is a major challenge for patients with SCD. It can be improved during clinic visits by reviewing missed doses and providing tools to aid daily compliance, such as smartphone medication apps, pillboxes and calendar reminders. Patients with SCD undergo repeated interventions that require intravenous access (laboratory analysis, fluid resuscitation, transfusions), and over time, peripheral venous access becomes difficult.31 Central venous access is often required, and it is important to educate the patient about the proper care of these devices and potential complications such as thrombosis and infection.
  • Psychosocial support. Patients with chronic illness face psychosocial stressors, and access to psychosocial support (psychologist, counselor, social worker) is of paramount importance in sustaining effective health maintenance strategies. Assistance can be provided for acquiring health insurance and transportation, joining support groups, and addressing educational and vocational goals.

Take-home messages

  • With new advances, health maintenance and curative therapies are available.
  • A team approach including the patient, caregivers, primary care physician and hematologists is crucial to optimizing disease outcomes.
  • The primary care physician is an important partner in providing optimal care to adults with SCD.

References

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