What is the management plan for a patient with thalassemia major?

Management of Thalassemia Major

Thalassemia major requires lifelong regular red blood cell transfusions every 3-4 weeks combined with daily iron chelation therapy, intensive cardiac surveillance, and consideration for hematopoietic stem cell transplantation as the only curative option. 1

Core Treatment Components

Regular Transfusion Therapy

• Transfuse packed red blood cells every 3-4 weeks to maintain hemoglobin >9 g/dL to suppress ineffective erythropoiesis and prevent skeletal deformities 1
• Patients require more than 8 transfusion events per year in adults to meet the definition of transfusion-dependent thalassemia major 1, 2
• Each transfused unit contains approximately 200-250 mg of elemental iron that accumulates without physiological excretion mechanisms 2

Iron Chelation Therapy

• Initiate iron chelation therapy as soon as regular transfusions are established to prevent iron accumulation in heart, liver, and endocrine organs 1
• Start chelation when serum ferritin consistently exceeds 1000 ng/mL after approximately 20-25 units of packed red blood cells 3
• Deferasirox (oral) is a first-line option: Start at 20 mg/kg/day, as doses below 20 mg/kg/day fail to provide consistent lowering of liver iron concentration and serum ferritin 4
• Alternative: Deferoxamine (subcutaneous) at 20-60 mg/kg/day for 5 days per week 4
• Deferiprone is another oral option available 5

Cardiac Surveillance (Critical for Mortality Prevention)

• Perform annual echocardiography and cardiac MRI T2 to detect early iron-related heart damage before symptoms develop* 1
• Cardiac iron loading accounts for approximately 70% of mortality in transfusion-dependent patients 1, 2
• Cardiac T2 <10 ms predicts heart failure: 98% of patients who developed heart failure had cardiac T2 <10 ms, and those with T2* <6 ms have a 50% likelihood of developing heart failure within 12 months without treatment intensification 3
• Perform cardiac T2* MRI screening for patients with high iron burden (liver iron content >15 mg/g dry weight) for ≥2 years, evidence of end-organ damage from transfusional iron overload, or evidence of cardiac dysfunction 3

Monitoring Iron Overload

• Monitor serum ferritin monthly while on chelation therapy 3
• Perform MRI for liver iron content every 1-2 years using validated R2, T2, or R2 methods** to guide chelation intensity, as ferritin alone is insufficient 3
• Long-term ferritin elevations >2500 μg/L predict cardiac mortality, but risk increases even at ferritin levels of 1000 μg/L 3

Critical Pitfall to Avoid

Do not rely on ferritin alone to assess cardiac risk—serum ferritin correlates poorly with cardiac iron loading in thalassemia, and a low ferritin does not guarantee freedom from heart failure 3. Inflammation (particularly from hepatitis C, which is highly prevalent in adult thalassemia patients) falsely elevates ferritin independent of iron stores 3.

Curative Treatment Option

Hematopoietic Stem Cell Transplantation (HSCT)

• HSCT is the only currently available cure for thalassemia major and should be performed as early as possible, ideally before age 14 years and before iron-related organ damage develops 1, 6
• Current outcomes show disease-free survival around 80% and overall survival over 90% 6, 1
• In young low-risk children transplanted from an HLA-matched sibling donor, transplant-related mortality has fallen to 5% or lower 6
• For patients with an HLA-identical sibling donor or well-matched related or unrelated donor, proceed as soon as possible to avoid transfusion-associated complications 6
• Disease-free survival is 96% in patients under age 14 years versus 82% in older patients 6

Screening for Viral Hepatitis

• Test all thalassemia patients who received blood transfusion before 1992 for anti-HCV antibodies 6
• Test for HBsAg and anti-HCV in patients with elevated serum aminotransferase levels for more than 6 months 6
• Confirm viral replication with qualitative serum HCV-RNA and quantitative serum HBV-DNA by PCR methods 6
• Patients with HBV or HCV and cirrhosis should receive liver ultrasound every 6 months for hepatocellular carcinoma surveillance, as they are at 6 times higher risk 6

Endocrine Monitoring

• Monitor growth and pubertal development carefully, particularly after age 10 years, as endocrine abnormalities frequently develop in patients with significant iron overload 7
• Manage endocrine complications in consultation with a pediatric or adult endocrinologist 7

Expected Outcomes

With optimal adherence to transfusions and chelation, survival into the fourth or fifth decade is now achievable for thalassemia major patients 1, 8. However, without treatment, death typically occurs by age 10 from cardiac complications 1, 2.