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

Management of Beta-Thalassemia Major

Beta-thalassemia major requires lifelong regular blood transfusions with appropriate iron chelation therapy as the cornerstone of management to prevent complications and improve survival. 1

Transfusion Therapy

Goals and Protocol

• Maintain pre-transfusion hemoglobin levels of 9-10 g/dL with post-transfusion levels of 13-14 g/dL 1
• This balance minimizes iron loading while maximizing symptom relief
• Transfusions should be administered every 2-4 weeks depending on individual needs
• Fresh blood (<14 days old) is preferred as it maintains higher pre-transfusion hemoglobin levels 2
• Monitor hemoglobin levels every 2 weeks during treatment 1

Transfusion Safety

• Perform extended red cell antigen typing (including CcEe and Kell) to reduce alloimmunization risk 3
• Implement leukoreduction when available to reduce transfusion reactions 3
• Screen blood products for transfusion-transmitted infections 3

Iron Chelation Therapy

Iron chelation is essential to prevent cardiac failure and other complications from iron accumulation. Three main chelators are available:

1. Deferasirox (oral)

• First-line oral chelator for many patients
• Starting dose: 20 mg/kg/day (doses below this level fail to consistently lower liver iron and serum ferritin) 4
• Advantages: Once-daily oral administration, improving compliance
• Monitor liver and kidney function regularly

2. Deferiprone (oral)

• Superior efficacy in removing cardiac iron compared to deferoxamine 1
• May increase risk of neutropenia during antiviral treatment 1
• Often used in combination therapy for severe cardiac iron overload

3. Deferoxamine (subcutaneous/intravenous)

• Traditional chelator administered via subcutaneous infusion (8-12 hours, 5-7 days/week)
• Recommended during antiviral treatment for hepatitis C when deferiprone is contraindicated 1
• For severe cardiac iron overload or heart failure: continuous 24-hour intravenous administration 1

Combination Therapy

• Combined deferiprone with deferoxamine shows superior efficacy versus deferoxamine alone 1
• Particularly effective for patients with cardiac iron overload or impaired left ventricular function

Monitoring Iron Overload

Cardiac Iron Assessment

• T2* cardiovascular magnetic resonance (CMR) is the gold standard for cardiac iron assessment 1
• Severe cardiac iron: T2* <10 ms (high risk for heart failure)
• Moderate cardiac iron: T2* 10-20 ms
• Normal: T2* >20 ms

Other Monitoring

• Serum ferritin: Regular monitoring to assess iron burden trend
• Liver iron concentration (LIC): By MRI or biopsy
• Cardiac function: Regular echocardiography or CMR
• Endocrine function: Annual screening for endocrinopathies

Management of Complications

Cardiac Complications

• For patients with T2* <6 ms: Treat aggressively even if asymptomatic (47% risk of heart failure within 1 year) 1
• For heart failure: Continuous 24-hour intravenous deferoxamine plus oral deferiprone 1
• Avoid excessive diuretics or inotropes due to unusual loading conditions in thalassemia 1

Hepatitis C Management

• Common in transfusion-dependent patients
• Combination treatment with Peg-interferon and ribavirin is recommended 1
• Expect 30-40% increase in transfusion requirements during treatment 1
• Switch to deferoxamine for chelation during antiviral treatment 1
• Monitor hemoglobin levels every 2 weeks and maintain >9 g/dL 1

Endocrine Complications

• Screen regularly for diabetes, hypothyroidism, hypoparathyroidism, and hypogonadism
• Provide appropriate hormone replacement therapy as needed

Curative Approaches

• Hematopoietic stem cell transplantation: Currently the only definitive cure 5
• Best outcomes when performed before significant iron overload or organ damage
• Gene therapy: Promising approach under investigation 6

Pitfalls and Caveats

1. Inadequate chelation leads to iron-induced cardiac disease, the primary cause of death in beta-thalassemia major 1
2. Delayed initiation of chelation therapy results in irreversible organ damage
3. Poor compliance with chelation therapy significantly increases mortality risk
4. Overuse of diuretics in thalassemia patients can worsen cardiac function due to unique loading conditions
5. Deferiprone may increase neutropenia risk during antiviral treatment 1
6. Patients with cardiovascular disease require close monitoring during antiviral treatment; those with decompensated myocardiopathy should avoid antiviral treatment 1

With proper transfusion support and iron chelation therapy, life expectancy of patients with beta-thalassemia major has dramatically improved over the past decades 5.