What are the treatment options for sickle cell disease?

Treatment Options for Sickle Cell Disease

The primary treatment options for sickle cell disease include hydroxyurea, L-glutamine, crizanlizumab, voxelotor, blood transfusions, and hematopoietic stem cell transplantation, with hydroxyurea being the first-line disease-modifying therapy for most patients. 1

Disease-Modifying Therapies

First-Line Therapy

• Hydroxyurea remains the cornerstone first-line therapy for most individuals with sickle cell disease (SCD) 1
  • Mechanism: Increases fetal hemoglobin production, reducing red blood cell sickling 1
  • Administration: Taken orally once daily as capsules or compounded liquid 2
  • Monitoring: Complete blood count (CBC) and reticulocyte count every 1-3 months to monitor for myelosuppression 2
  • Recommendation: Should be offered to children with HbSS or Sβ0-thalassemia by 9 months of age 2

Second-Line/Adjunctive Therapies

• L-glutamine (Endari)

  • FDA-approved for reducing pain events in SCD 2
  • Clinical benefit: Reduced hospitalization rates by 33% and mean length of stay from 11 to 7 days compared to placebo 1

• Crizanlizumab

  • Clinical benefit: Reduced pain crises from 2.98 to 1.63 per year compared to placebo 1

• Voxelotor

  • Clinical benefit: Increased hemoglobin by at least 1 g/dL in 51% of patients compared to 7% with placebo 1

Blood Transfusion Therapy

• Monthly red blood cell transfusions are indicated for:

  • Primary or secondary stroke prophylaxis 2
  • Recurrent complications not responding to other disease-modifying therapies 2

• Transfusion considerations:

  • Red blood cells should be matched for extended blood antigens (at least C, E, Kell) 2
  • Potential complications include febrile/allergic reactions, pathogen transmission, alloimmunization, and iron overload 2
  • Iron chelation therapy is required after 12-20 transfusions 2

• Perioperative transfusion strategies:

  • For high-risk surgeries: Exchange transfusion aiming for Hb of 100 g/L 2
  • For low/medium-risk surgeries in HbSS/HbSβ0 patients with baseline Hb <90 g/L: Top-up transfusion aiming for Hb of 100 g/L 2
  • For low/medium-risk surgeries in HbSS/HbSβ0 patients with baseline Hb ≥90 g/L: Partial exchange transfusion aiming for Hb of 100 g/L 2

Curative Approaches

• Hematopoietic stem cell transplantation (HSCT)

  • Currently the only curative therapy for SCD 2
  • Best outcomes achieved with HLA-matched sibling donors and when performed before 16 years of age 2
  • Main adverse effects: Infection, graft rejection, graft-versus-host disease, and potential infertility 2

• Gene therapy

  • Promising experimental approach using three strategies: gene addition, gene correction, and gene editing 2

Supportive Care and Complication Management

Infection Prevention and Management

• Prophylactic penicillin

  • Recommended for children with SCD 2
  • Can be discontinued after pneumococcal vaccine series is complete 2
  • Consider continuing in patients with history of invasive pneumococcal infection or surgical splenectomy 2

• Vaccination

  • Routine immunizations plus additional vaccines for children with functional asplenia 2

• Antibiotic therapy

  • Prompt and vigorous antibiotic therapy for infections 3
  • Patients with SCD are more susceptible to respiratory and wound infections 2

Pain Management

• Acute pain crises require effective analgesia 3
• Patients with SCD are not more likely to develop addiction to pain medications than the general population 1

Hydration Management

• Patients have impaired urinary concentrating ability and dehydrate easily 2
• Intravenous fluids should be 5% dextrose or 5% dextrose in 25% normal saline rather than normal saline due to reduced ability to excrete sodium load 3

Perioperative Care

• Maintain normothermia during perioperative period to prevent shivering and peripheral stasis 2
• Provide thromboprophylaxis for all peri- and post-pubertal patients 2
• Monitor oxygen saturation and maintain SpO2 above baseline or 96% (whichever is higher) for 24 hours postoperatively 2

Special Considerations

Pregnancy

• High-risk condition with increased complications:
  • Pre-eclampsia, intrauterine growth restriction, preterm labor, antepartum hemorrhage, and infection 2
  • Epidural analgesia is ideal for labor, particularly with opioid tolerance or sickle-related pain 2

Children

• Regular health maintenance should include:
  • Monitoring growth and development, cardiopulmonary status, hepatosplenomegaly, and neurologic status 2
  • Screening for proliferative retinopathy with annual dilated fundoscopic examinations beginning at 10 years of age 2
  • Educational support through 504 plans or individualized education programs 2

Emerging Therapies

• Clinical trials are ongoing for novel therapeutic approaches, particularly in gene therapy 2
• Multidisciplinary care is essential, with daily assessment by specialists after moderate or major surgery 2

Common Pitfalls and Caveats

• Avoid dehydration, especially in patients with pre-existing renal dysfunction 2
• Do not give continuous oxygen therapy unless necessary, but maintain adequate oxygenation 2
• Avoid hypothermia as it leads to shivering, peripheral stasis, hypoxia, and increased sickling 2
• Monitor for transfusion reactions in patients who have received blood transfusions 2