What is the management of thalassemia, particularly beta-thalassemia major?

Management of Beta-Thalassemia Major

The management of beta-thalassemia major requires a comprehensive approach centered on regular blood transfusions to maintain hemoglobin levels between 9-10 g/dL pre-transfusion, combined with appropriate iron chelation therapy to prevent iron overload complications. 1

Transfusion Therapy

• Transfusion Protocol:

  • Maintain pre-transfusion hemoglobin levels of 9-10 g/dL and post-transfusion target of 13-14 g/dL 1
  • Typically requires transfusions every 2-4 weeks 1
  • Monitor hemoglobin levels every 2 weeks during treatment 1
  • A moderate transfusion regimen (pre-transfusion Hb 9-10 g/dL) reduces blood consumption while still effectively suppressing erythropoiesis 2

• Benefits of Optimal Transfusion:

  • Prevents bone marrow expansion and extramedullary hematopoiesis
  • Promotes normal growth and development
  • Reduces cardiac workload
  • Improves quality of life

Iron Chelation Therapy

• Initiation Criteria:

  • Start when serum ferritin >1000 ng/mL 1
  • Usually begins after 10-20 transfusions

• Available Chelators:

  1. Deferoxamine (Desferal):

     • Parenteral administration (subcutaneous or intravenous)
     • Recommended during antiviral treatment 1
     • Used in pregnancy (second trimester) if needed 3

  2. Deferiprone (Ferriprox):

     • Oral administration
     • Superior efficacy for cardiac iron removal 1
     • May increase risk of neutropenia during antiviral treatment 1

  3. Deferasirox (Exjade, Jadenu):

     • Oral administration
     • Effective at doses of 20-30 mg/kg/day 4
     • Once-daily dosing improves compliance

  4. Combination Therapy:

     • Combined deferiprone with deferoxamine shows superior efficacy for cardiac iron overload 1
     • 24-hour continuous IV deferoxamine plus oral deferiprone for heart failure 1

Monitoring Iron Overload

• Cardiac Assessment:

  • T2* cardiovascular magnetic resonance (CMR) is the gold standard 1
  • Severe cardiac iron: T2* <10 ms
  • Moderate cardiac iron: T2* 10-20 ms
  • Normal: T2* >20 ms
  • Aggressive treatment needed for T2* <6 ms (47% risk of heart failure within 1 year) 1

• Liver Assessment:

  • Liver iron concentration (LIC) via biopsy or MRI
  • Ultrasound analysis every 6-12 months 3
  • Transient elastography (TE) if available 3

• Laboratory Monitoring:

  • Serum ferritin every 3 months
  • Liver function tests
  • Complete blood count (especially with deferiprone)

Management of Complications

Cardiac Complications

• Arrhythmias (particularly atrial fibrillation) are common in iron-overloaded patients 3
• For heart failure: continuous 24-hour IV deferoxamine plus oral deferiprone 1
• Avoid excessive diuretics due to unusual loading conditions in thalassemia 1

Hepatic Complications

• For HCV infection:

  • Combination therapy with Peg-interferon plus ribavirin 3
  • 48 weeks for genotypes 1/4; 24 weeks for genotypes 2/3 3
  • Withdraw therapy if HCV-RNA hasn't decreased by 2 log units after 12 weeks (genotypes 1/4) 3
  • Expect 30-40% increase in transfusion requirements during treatment 1

• For HBV infection:

  • Options include finite treatment with Peg-interferon, finite treatment with nucleoside/nucleotide analogs (NUCs), or long-term NUCs 3

Endocrine Complications

• Regular screening for diabetes, hypothyroidism, hypoparathyroidism, and hypogonadism 1
• Provide appropriate hormone replacement therapy as needed

Pregnancy Management in Thalassemia

• Assess heart T2* and cardiac function before conception 3
• Monitor heart function carefully during pregnancy 3
• Consider restarting iron chelation with deferoxamine in second trimester for severe iron overload 3
• Provide thromboembolism prophylaxis with heparin or low-molecular-weight heparin, especially in splenectomized patients 3
• Manage in expert centers due to increased risks to mother and baby 3

Important Considerations

• Delayed initiation of chelation therapy results in irreversible organ damage 1
• Poor compliance with chelation therapy significantly increases mortality risk 1
• Inadequate chelation leads to iron-induced cardiac disease, the primary cause of death in beta-thalassemia major 1
• Adherence to transfusion and chelation regimens is critical for long-term survival and quality of life