What is the recommended treatment for a patient with Thalassemia major?

Treatment of 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 cardiac death, which causes 70% of mortality in this disease. 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 prevent excessive marrow expansion 1
• Transfusion frequency: Every 3-4 weeks on a regular schedule 1

The moderate transfusion approach (pre-transfusion Hb 9-10 g/dL) reduces blood consumption by approximately 24% compared to hypertransfusion regimens, while still effectively suppressing erythropoiesis to only 2-3 times normal levels 2. This strategy significantly decreases iron loading and improves outcomes including spontaneous pubertal development 2.

Iron Chelation Therapy

Begin iron chelation immediately when regular transfusions are established - do not wait for iron overload to develop, as each unit of blood contains 200-250 mg of iron with no physiological excretion mechanism 1, 3.

First-line chelation options:

• Deferiprone (oral): 75 mg/kg/day - superior efficacy for cardiac iron removal compared to deferoxamine 4, 1
• Deferoxamine (subcutaneous): 50 mg/kg/day via subcutaneous infusion 5-7 nights per week 1
• Deferasirox (oral): Starting dose 20-30 mg/kg/day based on liver iron concentration - equivalent to deferoxamine for overall iron removal 4, 5

Critical evidence on chelator efficacy: Randomized controlled trials demonstrate deferiprone is superior to deferoxamine for cardiac iron removal, and combined deferiprone plus deferoxamine is superior to deferoxamine alone 4. Deferasirox doses below 20 mg/kg/day fail to provide consistent lowering of liver iron concentration and serum ferritin 5.

Cardiac Monitoring (The Target Organ)

Cardiac disease is the predominant cause of death in thalassemia major, accounting for approximately 70% of mortality 4, 3. Early detection and treatment of cardiac iron is easier and safer than treating late-stage heart failure when mortality risk is high 4.

Mandatory monitoring schedule:

• Cardiac MRI T2 annually* to detect cardiac iron before symptoms develop - this is the gold standard for cardiac iron assessment 1
• Echocardiography annually to assess left ventricular ejection fraction 1
• Serum ferritin every 3 months as a trend marker (note: this is a poor predictor of cardiac iron but useful for overall body iron trends) 1

Management of Acute Heart Failure

If acute heart failure develops, immediately transfer to a specialized thalassemia center and initiate intensive combination chelation:

• Continuous intravenous deferoxamine 50 mg/kg/day PLUS oral deferiprone 75 mg/kg/day 1

This aggressive dual-chelation approach is essential because cardiac iron overload with overt dysfunction requires maximal iron removal to reverse cardiomyopathy 4.

Infection Prevention

Before starting transfusions:

• Hepatitis B vaccination if not previously immunized 1
• Screen for hepatitis B and C regularly, as chronic viral hepatitis is common in transfused patients 1, 6

Transfusion-transmitted infections remain a significant risk, particularly in resource-limited settings where blood screening may be inadequate 6.

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, 7. Matched unrelated donor transplants now achieve results similar to matched sibling donors with advances in HLA typing 7. Despite complications such as graft-versus-host disease, the overall improvement in quality of life is substantial 7.

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. Before chelation therapy was available, patients with transfused but unchelated thalassemia typically died by age 10 from cardiac complications 3. The introduction of improved chelation has dramatically improved outcomes, with median age at death increasing to 35 years by 2000 3.

Common pitfall: Inadequate chelation remains the primary cause of preventable death. Many patients globally lack access to adequate iron chelation therapy and die from cardiac failure due to iron overload 6. Ensure chelation is started immediately with transfusions, not delayed until ferritin rises.