What are the primary treatment recommendations for a patient with beta-thalassemia major?

Management of Beta-Thalassemia Major

Initiate regular blood transfusions every 3-4 weeks maintaining pre-transfusion hemoglobin at 9-10 g/dL and post-transfusion hemoglobin at 13-14 g/dL, combined with immediate iron chelation therapy to prevent life-threatening cardiac complications. 1

Transfusion Protocol

Target hemoglobin levels:

• Pre-transfusion hemoglobin: 9-10 g/dL to balance iron loading minimization with symptom control 1, 2
• Post-transfusion hemoglobin: 13-14 g/dL to suppress ineffective erythropoiesis and reduce cardiac stress from chronic anemia 1, 2
• Transfusion frequency: Every 3-4 weeks on a regular schedule 1, 2

The evidence strongly supports this moderate transfusion regimen over hypertransfusion (baseline hemoglobin 10-12 g/dL). Research demonstrates that maintaining pre-transfusion hemoglobin at 9-10 g/dL reduces transfusion requirements from 137 to 104 mL/kg/year while decreasing mean serum ferritin from 2448 to 1187 μg/L, with half of patients achieving ferritin levels below 1000 μg/L. 3 This approach also increases spontaneous pubertal development without producing excessive erythroid marrow expansion. 3

Iron Chelation Therapy

Begin iron chelation immediately when regular transfusions are established - do not wait for iron overload to develop. 1, 2 Each unit of blood contains 200-250 mg of iron with no physiological excretion mechanism, and cardiac iron overload causes 70% of deaths in thalassemia. 1, 2

First-line chelation options:

• Deferoxamine (subcutaneous): 50 mg/kg/day via subcutaneous infusion 5-7 nights per week 1, 2
• Deferiprone (oral): 75 mg/kg/day 1, 2
• Deferasirox (oral): Starting dose 20-30 mg/kg/day based on liver iron concentration 2, 4

Deferasirox doses below 20 mg/kg/day fail to provide consistent lowering of liver iron concentration and serum ferritin levels. 4 The choice between agents depends on patient preference, adherence capability, and organ-specific iron distribution patterns.

Monitoring Requirements

Cardiac monitoring (highest priority given cardiac complications cause 71% of deaths): 5

• Annual cardiac MRI T2* to detect cardiac iron before symptoms develop 1, 2
• Annual echocardiography to assess left ventricular ejection fraction 1, 2

Iron burden monitoring:

• Serum ferritin every 3 months as a trend marker (though this is a low-quality marker) 1, 2
• Liver iron concentration via MRI to guide chelation therapy intensity 2, 6
• Liver function tests every 3 months to detect progressive liver damage and guide chelation intensification 6

Infection screening:

• Hepatitis B and C screening at baseline and regularly, as chronic viral hepatitis is common in transfused patients 2, 6
• Hepatitis B vaccination before starting transfusions if not previously immunized 1

Dietary Modifications

• Limit red meat consumption to reduce heme iron intake, which is highly absorbed 1
• Never take iron supplements or multivitamins containing iron 1

Curative Treatment

Hematopoietic stem cell transplantation (HSCT) is the only currently available cure and should be performed as early as possible, ideally before age 14 years and before iron-related organ damage develops. 1, 2, 7 This timing is critical because outcomes deteriorate significantly once organ damage from iron overload has occurred.

Management of Acute Cardiac Decompensation

If acute heart failure develops:

• Immediately transfer to a specialized thalassemia center 1
• Initiate continuous intravenous deferoxamine 50 mg/kg/day PLUS oral deferiprone 75 mg/kg/day (combination therapy for urgent cardiac iron removal) 1

Common Pitfalls to Avoid

Undertransfusion: Over 60% of regularly transfused patients have low pre-transfusion hemoglobin levels despite receiving large transfusion volumes, particularly in hemoglobin E β-thalassemia variants. 8 Monitor closely and adjust transfusion frequency rather than just volume.

Delayed chelation initiation: Waiting for ferritin elevation before starting chelation allows irreversible cardiac damage to develop. Begin chelation as soon as regular transfusions are established. 1, 2

Relying solely on serum ferritin: Serum ferritin is only a low-quality trend marker and does not accurately reflect cardiac or hepatic iron burden. Use cardiac MRI T2* and liver iron concentration for organ-specific assessment. 1, 2

Prognosis

With optimal adherence to transfusions and chelation, patients can expect survival into their 40s-50s with reasonable quality of life, compared to death by age 10 without treatment. 1