What are the management options for Sickle Cell Disease (SCD)?

Management Options for Sickle Cell Disease

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

Risk Stratification and Assessment

• Risk stratification is essential for guiding clinical decisions in SCD management 1
• Mortality risk can be determined by:
  • Tricuspid regurgitant velocity (TRV) > 2.5 m/second via Doppler echocardiography 1
  • NT-pro-BNP level > 160 pg/ml 1
  • Right heart catheterization (RHC)-confirmed pulmonary hypertension (mean pulmonary arterial pressure > 25 mm Hg) 1
• In children > 8 years old, TRV determines morbidity risk rather than mortality risk 1

First-Line Therapy

• Hydroxyurea (hydroxycarbamide) is strongly recommended as first-line therapy for patients with SCD who have increased mortality risk 1
  • Increases fetal hemoglobin production and reduces red blood cell sickling 2
  • Reduces frequency of acute painful vaso-occlusive episodes 3
  • Decreases hospitalization rates and improves quality of life 2
  • Prevents life-threatening neurological events in those at risk of primary stroke 3

Alternative and Adjunctive Therapies

• Chronic transfusion therapy is recommended for patients who are not responsive to or not candidates for hydroxyurea 1
• Newer FDA-approved therapies include:
  • L-glutamine: Reduces hospitalization rates by 33% and mean length of stay from 11 to 7 days compared to placebo 2
  • Crizanlizumab: Anti-P-selectin monoclonal antibody that reduced pain crises from 2.98 to 1.63 per year compared to placebo 2, 4
  • Voxelotor: Increases hemoglobin oxygenation and improved hemoglobin levels by at least 1 g/dL in 51% of patients versus 7% with placebo 2, 4

Management of Pulmonary Hypertension in SCD

• For patients with SCD who have RHC-confirmed PH, venous thromboembolism, and no additional risk factors for hemorrhage, indefinite anticoagulant therapy is suggested 1
• For patients with elevated TRV alone or elevated NT-pro-BNP alone, targeted PAH therapy is not recommended 1
• For select patients with RHC-confirmed PH with elevated pulmonary vascular resistance and normal pulmonary artery wedge pressure:
  • A trial of either prostacyclin agonist or endothelin receptor antagonist may be considered 1
  • Phosphodiesterase-5 inhibitor therapy is not recommended as first-line therapy 1

Perioperative Management

• Patients with SCD require specialized perioperative care including:
  • Adequate hydration to prevent sickling 1, 5
  • Maintenance of normothermia to prevent peripheral stasis 5
  • Thromboprophylaxis for all peri- and post-pubertal patients 5
  • Careful pain management 5
• Elective surgery should be performed in centers with experience in caring for SCD patients 1
• All patients at risk should be screened for hemoglobinopathy before surgery 1
• A nominated lead hematologist (or pediatrician/pediatric hematologist for children) should be responsible for the perioperative transfusion plan 1

Curative Options

• Hematopoietic stem cell transplant is the only curative therapy currently available 2
  • Best results seen in children with a matched sibling donor 2
  • Limited by donor availability 2, 6

Common Complications and Management

• Acute painful vaso-occlusive episodes: Require prompt pain management with analgesics and hydration 7
• Acute chest syndrome: Requires aggressive management including oxygen therapy, antibiotics, and possibly transfusion 2
• Stroke: Prevention through transcranial Doppler screening and prophylactic transfusions in high-risk children 3
• Chronic organ damage: Regular screening and early intervention for nephropathy, retinopathy, and other complications 2

Important Considerations

• Despite SCD being characterized by acute and chronic pain, patients are not more likely to develop addiction to pain medications than the general population 2
• Long-term effects of hydroxyurea on fertility and reproduction remain uncertain 3
• Evidence is limited regarding the effects of hydroxyurea on individuals with the HbSC genotype 3
• Transition from pediatric to adult-focused healthcare systems is associated with higher mortality 2