What are the management options for sickle cell disease?

Management of Sickle Cell Disease

The management of sickle cell disease requires a comprehensive approach focusing on prevention of complications, disease-modifying therapies, and prompt treatment of acute events to reduce morbidity and mortality.

Disease-Modifying Therapies

First-Line Therapy

• Hydroxyurea remains the first-line disease-modifying therapy for most patients with sickle cell disease 1
• Increases fetal hemoglobin production and reduces red blood cell sickling
• Consider for patients with frequent episodes of acute chest syndrome 2

Second-Line/Adjunctive Therapies

• L-glutamine is FDA-approved to reduce acute complications of sickle cell disease in patients 5 years and older 3
  • Clinical trials showed:
    • 25% reduction in cumulative crisis count
    • Reduced hospitalizations (median 2 vs 3 in placebo)
    • Shorter hospital stays (median 6.5 days vs 11 days)
    • Reduced incidence of acute chest syndrome (8.6% vs 23.1%)
  • Dosing based on weight:
    • <30 kg: 5g twice daily
    • 30-65 kg: 10g twice daily

    • 65 kg: 15g twice daily

• Other approved therapies include crizanlizumab and voxelotor 1

Management of Acute Complications

Acute Pain Crisis

• Prompt administration of opioid analgesics using scheduled dosing or patient-controlled analgesia 2
• Adjunctive non-opioid analgesics to avoid under-treatment of pain
• IV crystalloid fluids to maintain hydration (5% dextrose in 0.25% normal saline) 2
• Avoid excessive fluid administration to prevent pulmonary edema

Acute Chest Syndrome

• Defined by new pulmonary infiltrate on chest X-ray, fever and/or respiratory symptoms, often with decreasing hemoglobin and hypoxemia 2
• Management includes:
  • Supplemental oxygen to maintain SpO2 >95%
  • Broad-spectrum antibiotics covering typical and atypical pathogens
  • Red cell exchange transfusion for severe cases with respiratory failure, neurologic symptoms, or multi-organ failure
  • Simple transfusion may be considered for moderate cases 2

Infection Prevention and Management

• Broad-spectrum antibiotics should be started immediately if infection is suspected 2
• Delayed antibiotic administration increases morbidity and mortality
• Preventive measures include penicillin prophylaxis and appropriate vaccinations 4

Perioperative Management

• Meticulous perioperative care is essential to avoid factors that precipitate sickling 5:
  • Dehydration
  • Hypoxia
  • Acidosis
  • Hypothermia
  • Pain
• Routine surgery should be avoided if the patient is febrile or having a painful crisis 5
• Multidisciplinary collaboration between surgeon, anesthetist, and hematologist is imperative 2
• Consider admission to high dependency or intensive care postoperatively as most complications occur during this period 5

Special Populations

Pregnant Women

• Pregnancy confers increased risk for patients with sickle cell disease 5
• Management by a multidisciplinary team in hospitals able to manage high-risk pregnancies and sickle cell complications
• Epidural analgesia is ideal for labor, and regional anesthesia is preferred for cesarean section 2

Curative Options

• Hematopoietic stem cell transplant is the only curative therapy currently available 1
• Best results seen in children with a matched sibling donor
• Limited by donor availability

Long-Term Monitoring and Prevention

• Regular follow-up with a specialist hematology clinic
• Patient education on:
  • Importance of hydration
  • Avoiding temperature extremes
  • Medication adherence
  • Recognizing signs of emergencies requiring prompt medical attention 2

Prognosis

• Life expectancy has improved significantly but remains approximately 20 years less than the general population 2
• Mortality risk increases during transition from pediatric to adult care
• With optimal multidisciplinary care, survival into the 7th decade can be expected 5

The management of sickle cell disease has evolved significantly with improved understanding of the disease pathophysiology and the development of new therapies. A proactive approach to prevention of complications, coupled with prompt and aggressive management of acute events, is essential to improve quality of life and reduce mortality in patients with sickle cell disease.