What are the recommended management strategies for beta‑thalassemia (including major, intermedia, and minor)?

Management of Beta-Thalassemia

Begin regular blood transfusions every 3–4 weeks to maintain pre-transfusion hemoglobin at 9–10 g/dL and post-transfusion hemoglobin at 13–14 g/dL, combined with immediate initiation of iron chelation therapy, as cardiac iron overload causes 70% of deaths in beta-thalassemia major. 1, 2

Beta-Thalassemia Major: Core Treatment Algorithm

Transfusion Protocol

• Initiate regular red blood cell transfusions starting at 1–2 years of age when clinical symptoms emerge as fetal hemoglobin production declines. 1, 2
• Maintain pre-transfusion hemoglobin of 9–10 g/dL to balance iron loading minimization with adequate symptom control. 1
• Target post-transfusion hemoglobin of 13–14 g/dL to suppress ineffective erythropoiesis and prevent skeletal deformities and extramedullary hematopoiesis. 1
• Transfuse every 3–4 weeks on a fixed schedule rather than waiting for symptomatic anemia. 1

Iron Chelation Therapy: Critical for Survival

Start iron chelation as soon as regular transfusions are established—do not wait for iron overload to develop. Each transfused unit delivers 200–250 mg of elemental iron with no physiological excretion mechanism, making chelation mandatory for survival. 1, 2, 3

Chelator Selection Based on Cardiac Iron Status

For patients WITHOUT cardiac iron overload or heart failure:

• Deferasirox (oral) 20–30 mg/kg/day is equivalent to deferoxamine for overall iron removal and offers superior adherence due to once-daily oral dosing. 4, 3
• Deferoxamine (subcutaneous) 50 mg/kg/day via subcutaneous infusion 5–7 nights per week remains an alternative but requires nightly infusions. 1

For patients WITH cardiac iron overload (T2 <10 ms) but NO heart failure:*

• Deferiprone (oral) 75 mg/kg/day is superior to deferoxamine for removing cardiac iron deposits and should be the preferred agent. 4, 1

For patients WITH acute heart failure:

• Immediately transfer to a specialized thalassemia center and initiate combination therapy with continuous intravenous deferoxamine 50 mg/kg/day PLUS oral deferiprone 75 mg/kg/day. 4, 1
• Combined deferiprone plus deferoxamine is superior to deferoxamine alone for cardiac iron removal in this life-threatening situation. 4

Monitoring Requirements: Detect Problems Before Symptoms

Cardiac monitoring is non-negotiable because heart disease is the predominant cause of death in beta-thalassemia major. 4

• Annual cardiac MRI T2* to detect cardiac iron deposition before left ventricular dysfunction develops; T2* <10 ms is the most important predictor of heart failure development. 1
• Annual echocardiography to assess left ventricular ejection fraction, though interpretation is complicated by the high-output state from chronic anemia. 1
• Serum ferritin every 3 months as a trend marker only—it does NOT correlate reliably with cardiac iron and should never be used as the sole monitoring parameter. 1
• Liver iron concentration assessment annually, though it also does not predict cardiac iron burden. 4

Infection Prevention

• Administer hepatitis B vaccination before starting transfusions if not previously immunized. 1
• Screen for hepatitis B and C regularly as chronic viral hepatitis is common in multiply-transfused patients. 1

Dietary Modifications

• Limit red meat consumption to reduce heme iron intake, which has high bioavailability. 1
• Never prescribe iron supplements or multivitamins containing iron—this is a critical error that worsens iron overload. 1, 5

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, 6, 7

Beta-Thalassemia Intermedia: Selective Intervention

Patients with thalassemia intermedia generally do NOT require routine transfusions and should be managed conservatively unless complications develop. 4, 8

When to Initiate Transfusions in Intermedia

• Start regular transfusions if cardiovascular complications develop, including pulmonary hypertension, thrombosis, or progressive heart failure. 4
• Consider transfusions for severe extramedullary hematopoiesis causing spinal cord compression or disfiguring masses. 8, 9
• Initiate transfusions for growth retardation or severe skeletal deformities in children. 9

Iron Chelation in Intermedia

• Begin iron chelation when regular transfusions are established (same threshold as thalassemia major). 4
• Consider chelation even without transfusions if increased gastrointestinal iron absorption leads to documented iron overload on liver MRI or biopsy. 4, 8

Alternative Therapies for Intermedia

• Hydroxyurea may increase fetal hemoglobin production and reduce transfusion requirements in selected patients. 9
• Splenectomy can reduce transfusion burden but increases thrombotic risk. 8, 9

Beta-Thalassemia Minor (Trait): No Treatment Required

Patients with beta-thalassemia trait have microcytic, hypochromic anemia (MCV <80 fL) that does NOT respond to iron supplementation and requires no treatment. 2, 5

Critical Management Pitfall

• Never prescribe iron supplements to patients with confirmed thalassemia trait—this provides no therapeutic benefit and may contribute to unnecessary iron accumulation. 2, 5
• Genetic counseling is essential for reproductive planning, as two carriers have a 25% risk of having a child with thalassemia major. 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 Prior to modern iron chelation therapy, most patients died from cardiac complications by age 10; with optimal chelation, survival into the seventh decade is now achievable. 2