Treatment of Beta Thalassemia
Beta thalassemia major requires lifelong regular blood transfusions every 3-4 weeks combined with immediate iron chelation therapy to prevent cardiac death, which historically caused 70% of mortality in these patients. 1, 2
Core Treatment Strategy
Blood Transfusion Protocol
- Maintain pre-transfusion hemoglobin at 9-10 g/dL to suppress ineffective erythropoiesis while minimizing iron loading 1, 2
- Target post-transfusion hemoglobin of 13-14 g/dL to adequately suppress bone marrow expansion and reduce cardiac workload 1, 2
- Transfuse every 3-4 weeks on a fixed schedule rather than waiting for symptoms to develop 2
The rationale for these specific targets is that they balance symptom control with iron accumulation—each unit of blood contains 200-250 mg of iron with no physiological mechanism for excretion 2, 3. Before transfusion therapy became standard, patients died by age 10 from severe anemia and cardiac complications 2.
Iron Chelation Therapy
Begin iron chelation immediately once regular transfusions are established, not after waiting for iron overload to develop 2. This is critical because cardiac iron overload remains the leading cause of death even in the modern era 1.
First-Line Chelation Options:
- Deferoxamine (subcutaneous): 50 mg/kg/day via subcutaneous infusion 5-7 nights per week 2
- Deferiprone (oral): 75 mg/kg/day divided into three daily doses 2
- Deferasirox (oral): Equivalent efficacy to deferoxamine based on randomized controlled trials 1
For cardiac iron overload without overt dysfunction, deferiprone shows superior efficacy versus deferoxamine in removing cardiac iron 1. Combined deferiprone plus deferoxamine is superior to deferoxamine alone for cardiac iron clearance 1.
Monitoring Requirements
Cardiac disease is easier and safer to treat early rather than late when mortality risk is high 1. Therefore, aggressive monitoring is essential:
- Annual cardiac MRI T2* to detect cardiac iron deposition before symptoms develop—severe cardiac iron loading is defined as T2* <10 ms, mild-to-moderate as 10-20 ms 1, 2
- Annual echocardiography to assess left ventricular ejection fraction and detect early dysfunction 2
- Serum ferritin every 3 months as a trend marker (though it correlates poorly with cardiac iron specifically) 2
- Liver function tests every 3 months to detect progressive hepatic iron damage and guide chelation intensity 3
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 2. This timing is critical because outcomes deteriorate significantly once cardiac or hepatic complications occur.
Management of Acute Cardiac Decompensation
If acute heart failure develops, immediately transfer to a specialized thalassemia center and initiate continuous intravenous deferoxamine 50 mg/kg/day PLUS oral deferiprone 75 mg/kg/day 2. This intensive combined chelation approach is necessary because cardiac iron clearance substantially lags improvements in systolic function, creating high relapse risk with premature termination 1.
Standard heart failure medications (diuretics, inotropes) require careful adjustment due to the unusual loading conditions in thalassemia patients 1.
Infection Prevention
- Hepatitis B vaccination before starting transfusions if not previously immunized 2
- Regular screening for hepatitis B and C, as chronic viral hepatitis is common in chronically transfused patients and contributes to liver dysfunction 2, 3
Dietary Modifications
- Never take iron supplements or multivitamins containing iron—this is an absolute contraindication 2
- Limit red meat consumption to reduce heme iron intake, which has high bioavailability 2
Common Pitfalls to Avoid
Do not wait for symptoms or ferritin elevation before starting chelation—begin immediately with regular transfusions 2. Cardiac iron deposition can occur even with normal ferritin levels, and by the time heart failure symptoms appear, mortality risk is substantially elevated 1.
Do not rely solely on serum ferritin to guide cardiac chelation—cardiac MRI T2* is essential because ferritin correlates poorly with cardiac iron specifically 1, 2. Patients can have severe cardiac iron with relatively modest ferritin elevation.
Do not undertransfuse in an attempt to reduce iron loading—maintaining hemoglobin below 9 g/dL leads to increased cardiac output, bone marrow expansion, and extramedullary hematopoiesis, which worsen outcomes 1, 4.
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 2. In the United Kingdom by 2000, median age at death improved to 35 years with deferoxamine treatment, and continues to improve with newer chelation strategies 1.
Emerging Therapies
Gene therapy, gene editing, and luspatercept represent promising approaches targeting the underlying globin chain imbalance and ineffective erythropoiesis 5, 6, 4. However, these remain investigational and are not yet standard of care outside clinical trials.