What is the primary treatment for sickle cell disease?

Primary Treatment for Sickle Cell Disease

Hydroxyurea is the primary disease-modifying therapy for sickle cell disease and should be offered to all patients with HbSS or HbSβ0-thalassemia genotypes, starting as early as 9 months of age. 1, 2

First-Line Treatment: Hydroxyurea

Hydroxyurea works through multiple mechanisms to improve outcomes in sickle cell disease:

• Increases fetal hemoglobin (HbF) production, which inhibits sickling of red blood cells 3
• Reduces white blood cell count, which decreases inflammation and vaso-occlusive events 4
• Decreases the frequency of painful crises, acute chest syndrome, and hospitalizations 2, 5
• Improves overall survival and quality of life 5

Dosing and Administration

• Starting dose typically 15-20 mg/kg/day as a single daily oral dose 6, 4
• Dose may be escalated to maximum tolerated dose based on laboratory parameters 5
• Requires regular monitoring of complete blood count every 1-3 months 1
• Dose reduction needed for patients with renal impairment (CrCl <60 mL/min) 6

Monitoring Parameters

• Complete blood count with reticulocyte count every 1-3 months 1
• Renal and liver function tests periodically 6
• Target hemoglobin level should not exceed 10 g/dL when used with erythropoiesis-stimulating agents to reduce risk of vaso-occlusive complications 1, 7

Additional Disease-Modifying Therapies

For patients who cannot tolerate hydroxyurea or have inadequate response, additional options include:

• L-glutamine (Endari): Approved for patients 5 years and older to reduce pain events 1, 2

  • Mechanism: Reduces oxidative stress in red blood cells 1
  • Administered as powder packets mixed with liquid or food twice daily 1

• Chronic transfusion therapy: Recommended for specific indications 1

  • Primary or secondary stroke prevention 1
  • Recurrent acute chest syndrome unresponsive to hydroxyurea 1
  • Requires monitoring for iron overload and alloimmunization 1

Management of Specific Complications

Pulmonary Hypertension

• For patients with confirmed pulmonary hypertension, hydroxyurea is strongly recommended 1
• For patients with venous thromboembolism and pulmonary hypertension, indefinite anticoagulation is suggested 1
• Targeted pulmonary arterial hypertension therapies are generally not recommended 1

Renal Disease

• For patients with worsening anemia associated with chronic kidney disease, combination therapy with hydroxyurea and erythropoiesis-stimulating agents is recommended 1
• Blood pressure goal of ≤130/80 mmHg is recommended for adults with SCD 1

Infection Prevention

• Penicillin V potassium prophylaxis (125 mg orally twice daily) starting at 2 months of age for all infants with HbSS and Sβ0-thalassemia 1
• Dose increases to 250 mg orally twice daily at 3 years of age and continued until age 5 years 1
• Vaccination against encapsulated organisms, including pneumococcal and meningococcal vaccines 1

Curative Therapies

• Hematopoietic stem cell transplantation: Currently the only curative therapy 2
  • Best outcomes achieved with HLA-matched sibling donors before 16 years of age 2
  • Limited by donor availability and potential complications 2

Common Pitfalls and Caveats

• Underutilization of hydroxyurea despite strong evidence supporting its efficacy and safety 5
• Inadequate dose optimization leading to suboptimal clinical response 8
• Concerns about potential side effects (e.g., myelosuppression, teratogenicity) that may be mitigated with appropriate monitoring 6, 5
• Failure to recognize that hydroxyurea may take 3-6 months to achieve maximal clinical benefit 5
• Discontinuation of therapy due to temporary myelosuppression rather than appropriate dose adjustment 6

Hydroxyurea remains the cornerstone of sickle cell disease management with the strongest evidence base for improving morbidity, mortality, and quality of life 2, 5, 3.