What is the initial treatment for sickle cell anaemia?

Initial Treatment for Sickle Cell Anemia

Hydroxyurea is the primary disease-modifying therapy recommended for all patients with sickle cell anemia (HbSS or HbSβ0-thalassemia genotypes), starting as early as 9 months of age. 1

First-Line Treatment: Hydroxyurea

Hydroxyurea offers significant benefits for patients with sickle cell anemia by:

• Increasing fetal hemoglobin (HbF) production, which reduces sickling of red blood cells 2
• Reducing the frequency of painful vaso-occlusive crises 3, 4
• Decreasing the incidence of acute chest syndrome 4
• Reducing the need for blood transfusions 4, 5
• Lowering mortality rates in patients with increased risk for mortality 3

Dosing and Administration

• Initial dosing typically starts at 15-20 mg/kg/day 6, 4
• Dose can be escalated to maximum tolerated dose (up to 30 mg/kg/day) based on laboratory parameters 6, 7
• Regular monitoring with complete blood count every 1-3 months is required 1

Additional Disease-Modifying Therapies

L-glutamine (Endari)

• FDA-approved for patients 5 years and older to reduce acute complications of sickle cell disease 8
• Recommended dosage based on weight:
  • Less than 30 kg: 5 g twice daily
  • 30-65 kg: 10 g twice daily
  • Greater than 65 kg: 15 g twice daily 8

Crizanlizumab (Adakveo)

• Indicated to reduce the frequency of vaso-occlusive crises in adults and pediatric patients aged 16 years and older 9
• Administered at 5 mg/kg by intravenous infusion on Week 0, Week 2, and every 4 weeks thereafter 9

Chronic Transfusion Therapy

• Recommended for specific indications, including:
  • Primary or secondary stroke prevention
  • Recurrent acute chest syndrome unresponsive to hydroxyurea 1
• Goal hemoglobin concentration of 10-12 g/dl is often attainable 3
• Risks include febrile reactions, allergic reactions, hemolytic reactions, and iron accumulation 3

Management of Specific Complications

Pulmonary Hypertension

• Hydroxyurea is strongly recommended for patients with confirmed pulmonary hypertension or increased risk of mortality (TRV >2.5 m/second, NT-pro-BNP >160 pg/ml, or RHC-confirmed PH) 3
• This recommendation is based on moderate-quality evidence showing reduced mortality with hydroxyurea therapy 3

Renal Disease

• Combination therapy with hydroxyurea and erythropoiesis-stimulating agents is recommended for patients with worsening anemia associated with chronic kidney disease 1, 10
• Target hemoglobin should not exceed 10 g/dL to reduce risk of vaso-occlusive complications 10

Monitoring and Safety Considerations

• Laboratory toxicities with hydroxyurea are typically mild, transient, and reversible upon temporary discontinuation 6
• Common adverse reactions with L-glutamine include constipation (21%), nausea (19%), headache (18%), and abdominal pain (17%) 8
• Infusion-related reactions may occur with crizanlizumab; monitoring during administration is necessary 9

Special Populations

Pediatric Patients

• Hydroxyurea has demonstrated safety and efficacy in children as young as 9 months 1, 6
• Studies in sub-Saharan Africa have shown significant benefits of hydroxyurea in reducing vaso-occlusive events, infections, malaria, transfusions, and death in children 4, 7
• L-glutamine is approved for children 5 years and older 8
• Crizanlizumab is approved for patients 16 years and older 9

Pregnancy

• Limited data available on L-glutamine use in pregnant women 8
• Careful consideration of risks and benefits is necessary when using these medications during pregnancy

Pitfalls and Caveats

• Hydroxyurea has no role in the treatment of crises already in progress; it is a preventive therapy 2
• Regular monitoring is essential to detect and manage potential toxicities 1, 6
• Patient adherence is critical for achieving optimal benefits 2
• Iron accumulation is a significant concern with chronic transfusion therapy; monitoring of serum ferritin levels is necessary 3