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

First-Line Disease-Modifying Therapy

• Hydroxyurea remains the cornerstone of treatment for most individuals with sickle cell disease, functioning by increasing fetal hemoglobin levels and reducing red blood cell sickling 2
• The American Academy of Pediatrics specifically recommends initiating hydroxyurea in infants as young as 9 months of age with HbSS or HbSβ0-thalassemia genotypes 1
• This medication works by inhibiting DNA synthesis through ribonucleotide reductase inhibition, ultimately increasing fetal hemoglobin production 3

Clinical Benefits

• Hydroxyurea reduces pain crisis frequency, duration, and intensity, along with decreasing hospital admissions and opioid requirements 1
• The medication decreases acute chest syndrome episodes by approximately 80% in pediatric patients 4
• Blood transfusion requirements are significantly reduced with hydroxyurea therapy 4, 5
• Hospitalizations for painful events decrease by approximately 30% compared to pre-treatment periods 4

Essential Monitoring Requirements

• Complete blood count monitoring every 1-3 months is mandatory for all patients receiving hydroxyurea 1
• Bone marrow suppression (decreased counts in one or more cell lines) commonly occurs and requires temporary discontinuation if severe 6
• When used with erythropoiesis-stimulating agents, target hemoglobin should not exceed 10 g/dL to reduce vaso-occlusive complication risk 1, 6

Additional Disease-Modifying Options

Second-Line Therapies

• L-glutamine (Endari) is approved for patients ≥5 years old to reduce pain events through reduction of oxidative stress in red blood cells, demonstrating a 33% reduction in hospitalization rates 1, 2
• Crizanlizumab reduces pain crises from 2.98 to 1.63 per year compared to placebo 2
• Voxelotor increases hemoglobin by at least 1 g/dL in 51% of patients versus 7% with placebo 2

Chronic Transfusion Therapy

• Reserved for specific indications including primary or secondary stroke prevention and recurrent acute chest syndrome unresponsive to hydroxyurea 1

Infection Prophylaxis

• Penicillin V potassium prophylaxis must be started at 2 months of age for all infants with HbSS and Sβ0-thalassemia 1
• This represents a critical component of comprehensive care alongside hydroxyurea therapy

Special Populations

Renal Impairment

• Hydroxyurea exposure increases by 64% in patients with creatinine clearance <60 mL/min or end-stage renal disease 3
• Dose reduction is required for patients with CrCl <60 mL/min or ESRD following hemodialysis 3
• Combination therapy with hydroxyurea and erythropoiesis-stimulating agents is recommended for patients with chronic kidney disease and worsening anemia 1, 6
• Blood pressure goal of ≤130/80 mmHg should be maintained in adults with SCD 1

Pulmonary Hypertension

• Hydroxyurea is strongly recommended for patients with confirmed pulmonary hypertension 1

Important Caveats

• Hydroxyurea may not prevent complications once organ damage is established, as recurrent acute splenic sequestration and progressive symptomatic osteonecrosis have been observed during therapy 4
• The medication is mutagenic and clastogenic, with potential effects on fertility (testicular atrophy and decreased spermatogenesis observed in animal studies at 0.3 times the maximum human dose) 3
• Despite 30 years of accumulated evidence demonstrating safety and efficacy, hydroxyurea remains underutilized in clinical practice 7
• Linear growth continues unchanged and patients gain weight appropriately during therapy 4

Curative Option

• Hematopoietic stem cell transplant remains the only curative therapy but is limited by donor availability, with best results in children with matched sibling donors 2