What is the treatment for sickle cell anemia?

Treatment of Sickle Cell Anaemia

Hydroxyurea (hydroxycarbamide) is the first-line disease-modifying therapy for sickle cell disease and should be offered to all patients with HbSS or HbSβ0-thalassemia from 9 months of age, even without clinical symptoms. 1, 2

Disease-Modifying Therapies

First-Line Therapy: Hydroxyurea

• Mechanism of action: Increases fetal hemoglobin (HbF) production, which reduces HbS polymerization and sickling
• Benefits:
  • Reduces frequency of painful crises by approximately 50% 3
  • Decreases hospitalizations by 30% 4
  • Reduces acute chest syndrome episodes by 80% 4
  • Decreases need for blood transfusions 4, 3
  • Improves survival and quality of life 2
• Dosing:
  • Starting dose: 10-15 mg/kg/day orally once daily 5
  • Dose can be gradually increased based on response and tolerance
  • Target HbF level >8% for optimal protection 2
• Monitoring:
  • Complete blood count and reticulocyte count every 1-3 months
  • Monitor for myelosuppression (primary side effect) 1

Second-Line/Adjunctive Therapies

1. L-glutamine (Endari):

   • FDA-approved for patients ≥5 years old 6
   • Dosing based on weight:
     • <30 kg: 5g twice daily
     • 30-65 kg: 10g twice daily

     • 65 kg: 15g twice daily 6

   • Benefits: Reduces acute complications, hospitalizations (33% reduction), and hospital length of stay (from 11 to 7 days) 6, 7

2. Chronic Transfusion Therapy:

   • Indications:
     • Stroke prevention (primary or secondary)
     • Recurrent acute chest syndrome
     • Recurrent severe pain crises not responding to hydroxyurea 1
   • Goal: Maintain HbS <30% and hemoglobin 10-12 g/dL 1
   • Complications: Iron overload (requiring chelation after 12-20 transfusions), alloimmunization, transfusion reactions 1

3. Combination Therapy:

   • For patients with SCD and chronic kidney disease with worsening anemia, consider combination of hydroxyurea and erythropoiesis-stimulating agents 1
   • Allows for more aggressive hydroxyurea dosing while managing anemia 1
   • Hemoglobin threshold should not exceed 10 g/dL to avoid vaso-occlusive complications 1

Curative Therapies

Hematopoietic Stem Cell Transplantation (HSCT):

• Only curative treatment currently available 1, 7
• Best outcomes with HLA-matched sibling donors and when performed before 16 years of age 1
• Complications: Graft rejection, graft-versus-host disease, infection, infertility 1

Management of Complications

Acute Pain Crisis

• Prompt pain management with appropriate analgesics
• Hydration
• Continue hydroxyurea during crises 2

Acute Chest Syndrome

• Supplemental oxygen
• Antibiotics
• Simple or exchange transfusion for severe cases
• Hydroxyurea reduces incidence by up to 80% 4

Cardiovascular/Renal Management

• Blood pressure goal of 130/80 mmHg for adults with SCD (strong recommendation) 1
• Regular screening for proteinuria and renal function 1

Perioperative Management

• Optimize hydroxyurea therapy
• Consider preoperative transfusion for high-risk procedures 1
• Maintain adequate hydration and oxygenation 1

Preventive Care

• Prophylactic penicillin for children until at least 5 years of age 1
• Complete pneumococcal vaccination series 1
• Annual influenza vaccination
• Regular ophthalmologic examinations beginning at age 10 1
• Screening for pulmonary hypertension in adults 1

Pitfalls and Caveats

1. Underutilization of hydroxyurea: Despite strong evidence for efficacy and safety, hydroxyurea remains underutilized 8. Early initiation can alter the natural history of SCD.

2. Delayed effect of hydroxyurea: Benefits may not become apparent for several months after initiation 3.

3. Pain management misconceptions: SCD patients are not more likely to develop addiction to pain medications than the general population 7.

4. Transition from pediatric to adult care: Higher mortality occurs during this transition period, requiring careful coordination of care 7.

5. Hydroxyurea limitations: May not prevent complications once organ damage is present 4. Regular monitoring for development of complications is still necessary.