What are the guidelines for managing sickle cell disease?

Management Guidelines for Sickle Cell Disease

Hydroxyurea is strongly recommended as first-line therapy for patients with sickle cell disease who have an increased risk for mortality, while chronic transfusion therapy is suggested as an alternative for those who are not responsive to or not candidates for hydroxyurea. 1

Risk Stratification and Mortality Assessment

Risk stratification is essential for guiding clinical decisions in sickle cell disease (SCD). Patients at increased mortality risk can be identified through:

• Noninvasive measurements:
  • Tricuspid regurgitant jet velocity (TRV) ≥ 2.5 m/second via Doppler echocardiography
  • N-terminal pro-brain natriuretic peptide (NT-pro-BNP) level ≥ 160 pg/ml
• Invasive measurement:
  • Right heart catheterization (RHC)-confirmed pulmonary hypertension (PH) with mean pulmonary arterial pressure > 25 mm Hg 1

Treatment Recommendations

Disease-Modifying Therapies

1. Hydroxyurea (First-line therapy)

   • Strong recommendation for patients with increased mortality risk 1
   • Strong recommendation for adults with:
     • 3+ severe vaso-occlusive crises during any 12-month period
     • SCD pain or chronic anemia interfering with daily activities
     • Severe or recurrent episodes of acute chest syndrome 2
   • Moderate strength recommendation for infants, children, and adolescents without regard to symptoms 2
   • Increases fetal hemoglobin and reduces red blood cell sickling 3

2. Chronic Transfusion Therapy

   • Weak recommendation for patients with increased mortality risk who are not responsive to or not candidates for hydroxyurea 1
   • Strong recommendation for stroke prevention in children with abnormal transcranial Doppler velocity (≥200 cm/s) 2
   • For long-term transfusion therapy, maintain sickle hemoglobin levels < 30% prior to next transfusion (moderate strength recommendation) 2

3. Newer Therapies (adjunctive or second-line)

   • L-glutamine: Reduced hospitalization rates by 33% in clinical trials
   • Crizanlizumab: Reduced pain crises from 2.98 to 1.63 per year
   • Voxelotor: Increased hemoglobin by at least 1 g/dL in 51% of patients 3

Pulmonary Hypertension Management

• Strong recommendation against PAH-specific therapy for:

  • Patients with elevated TRV alone or elevated NT-pro-BNP alone
  • Patients with RHC-confirmed PH with elevated pulmonary artery wedge pressure and low pulmonary vascular resistance 1

• Weak recommendation for prostacyclin agonist or endothelin receptor antagonist therapy in select patients with:

  • RHC-confirmed PH with elevated pulmonary vascular resistance and normal pulmonary capillary wedge pressure 1

• Strong recommendation against phosphodiesterase-5 inhibitor therapy 1

Anticoagulation

• Weak recommendation for indefinite anticoagulant therapy for patients with:
  • RHC-confirmed PH
  • Venous thromboembolism
  • No additional risk factors for hemorrhage 1

Management of Acute Complications

Pain Management

• Administer opioid analgesics promptly using scheduled dosing or patient-controlled analgesia 4
• Consider adjunctive non-opioid analgesics to avoid under-treatment of pain 4
• NSAIDs and opioids are the mainstay of pain treatment 5
• Additional therapies include hydration, local pain control, muscle relaxants, and non-pharmacologic approaches 5

Infection Management

• Immediate initiation of broad-spectrum antibiotics if infection is suspected 4
• Coverage should include typical and atypical pathogens, including those responsible for community-acquired pneumonia, Mycoplasma, and Chlamydia 4
• Draw blood cultures and start antibiotics if temperature ≥ 38.0°C or signs of sepsis 4
• Daily prophylactic penicillin up to age 5 years (strong recommendation) 2

Acute Chest Syndrome

• Characterized by new pulmonary infiltrates on chest X-ray, fever, respiratory symptoms, decreasing hemoglobin, and hypoxemia 4
• Exchange transfusion (manual or automated) is the treatment of choice for severe cases 4
• Simple transfusion or exchange transfusion may be used for moderate cases 4
• Provide supplemental oxygen to maintain SpO2 >95% 4

Neurological Complications

• Annual transcranial Doppler examinations from ages 2 to 16 years in those with sickle cell anemia (strong recommendation) 2
• Patients with neurological symptoms should undergo immediate neuroimaging, rapid exchange transfusion, and neurological consultation 4

Preventive Measures

• Education on hydration, avoiding extreme temperatures, and medication adherence 4
• Pneumococcal vaccination and prophylactic antibiotics to decrease bacteremia risk 4
• Regular monitoring for complications:
  • Transcranial Doppler screening for stroke risk
  • SpO2 monitoring for early detection of acute chest syndrome
  • Echocardiography to evaluate signs of pulmonary hypertension 4

Long-Term Care and Prognosis

• With optimal multidisciplinary care, survival into the 7th decade can be expected 4
• Life expectancy has improved significantly but remains approximately 20 years less than the general population 4, 3
• Strong recommendations for chronic complications:
  • Analgesics and physical therapy for avascular necrosis
  • ACE inhibitor therapy for microalbuminuria in adults
  • Referral to specialists for proliferative sickle cell retinopathy 2

Common Pitfalls and Caveats

1. Underutilization of disease-modifying therapies - Despite proven benefits, hydroxyurea and long-term blood transfusions remain underused 2

2. Inadequate pain management - Pain should be treated aggressively to prevent worsening of crisis 4, 5

3. Excessive fluid administration - Should be avoided to prevent pulmonary edema 4

4. Delayed antibiotic treatment - Fever ≥38°C requires immediate medical attention due to high risk for septicemia and meningitis 4

5. Bias in care delivery - Since SCD largely affects racialized minorities in the US, healthcare providers need to be aware of how personal biases may affect care 5

6. Transition from pediatric to adult care - Higher mortality occurs as individuals transition between healthcare systems 3