What is the treatment for a patient with Thalassemia (a genetic disorder affecting hemoglobin production)?

Treatment of Thalassemia

For β-thalassemia major, initiate lifelong regular blood transfusions to maintain pre-transfusion hemoglobin of 9-10 g/dL combined with mandatory lifelong iron chelation therapy, while considering hematopoietic stem cell transplantation (HSCT) as the only curative option for eligible patients with an HLA-matched sibling donor, ideally performed in early childhood before iron-related organ damage develops. 1

β-Thalassemia Major: Core Treatment Strategy

Regular Blood Transfusions

• Maintain pre-transfusion hemoglobin levels of 9-10 g/dL with post-transfusion levels of 13-14 g/dL to suppress ineffective erythropoiesis and prevent complications from chronic anemia 1
• Transfusions are required lifelong, typically starting at 1-2 years of age when fetal hemoglobin production declines 2
• The transfusion regimen balances minimization of iron loading against maximization of symptom relief and prevention of bone marrow expansion 1

Mandatory Iron Chelation Therapy

• Iron chelation is required lifelong because each unit of transfused blood contains approximately 200-250 mg of elemental iron, and humans lack physiological mechanisms for iron excretion 2, 3
• Deferasirox (oral chelator) at starting doses of 20-30 mg/kg/day provides consistent lowering of liver iron concentration (LIC) and serum ferritin levels; doses below 20 mg/kg/day fail to provide consistent benefit 3
• Deferoxamine (subcutaneous/intravenous) remains an alternative chelation option, particularly during antiviral therapy for hepatitis C when deferiprone may increase neutropenia risk 1
• Early cardiac disease from iron overload is easier and safer to treat than late-stage disease, which carries high mortality risk; cardiac iron overload accounts for approximately 70% of deaths in transfusion-dependent patients 1, 2

Hematopoietic Stem Cell Transplantation (HSCT): The Only Cure

• HSCT is the only curative treatment currently available and should be considered for all eligible patients with β-thalassemia major who have an HLA-matched sibling donor 1
• Perform HSCT as early as possible in childhood (ideally in the first years of life) before iron-related complications develop, as patient status at transplantation is the critical predictor of outcome 1
• Modern transplantation approaches in young, low-risk children with HLA-matched sibling donors achieve overall survival and disease-free survival of 91% with transplant-related mortality of 5% or lower 1
• The Pesaro risk classification identifies three risk factors (hepatomegaly, portal fibrosis, inadequate chelation) that predict transplant outcomes; transplant in low-risk patients yields superior results 1

β-Thalassemia Intermedia

• Patients generally do not require regular transfusions to maintain hemoglobin levels initially 1
• As patients age, transfusions may become necessary to prevent cardiovascular complications, pulmonary hypertension, and thrombosis 1
• Once transfusions begin, iron chelation therapy becomes necessary due to transfusional iron loading 1

α-Thalassemia Management by Severity

Hemoglobin H Disease (3-gene deletion)

• Monitor with complete blood count every 3-6 months to assess for worsening hemolytic anemia 4
• Transfusions may be required episodically based on severity of anemia 5, 6
• Iron chelation therapy is needed if transfusion-dependent 5

Hemoglobin Bart's Hydrops Fetalis (4-gene deletion)

• This condition is typically fatal, resulting in severe intrauterine hypoxia and non-immune hydrops fetalis in late second or early third trimester 4
• Intrauterine transfusion is considered investigational and not generally recommended outside research settings 4
• Prenatal diagnosis is critical when both parents are carriers to allow informed reproductive decision-making 4

α-Thalassemia Trait (1-2 gene deletions)

• Asymptomatic carrier state requiring no treatment 7, 6
• Do not prescribe iron supplementation—it provides no benefit and may contribute to unnecessary iron accumulation 8

Critical Monitoring and Complication Prevention

Cardiac Surveillance

• Regular cardiac monitoring is essential as cardiac iron overload is the leading cause of death 1, 2
• T2* cardiovascular magnetic resonance imaging can assess cardiac iron loading; values <10 ms indicate severe cardiac iron overload requiring intensified chelation 1
• Treat cardiac disease early rather than waiting for late-stage heart failure, which carries high mortality 1

Hepatic Complications

• For patients with chronic hepatitis C, combination treatment with pegylated interferon and ribavirin achieves sustained virologic response in 64% of patients with genotypes 1 or 4 1
• During antiviral therapy, switch to deferoxamine for iron chelation as deferiprone increases neutropenia risk 1
• Monitor hemoglobin every 2 weeks during antiviral therapy and increase transfusions to maintain hemoglobin >9 g/dL 1

Common Pitfalls to Avoid

• Never give iron supplementation to confirmed thalassemia trait patients—the microcytic anemia does not respond to iron therapy, distinguishing it from iron deficiency 8
• Do not delay HSCT in eligible young patients waiting for gene therapy, which remains investigational; patient outcomes worsen with age and development of iron-related organ damage 1
• Do not underestimate transfusion requirements—inadequate transfusion leads to bone marrow expansion, extramedullary hematopoiesis, and skeletal deformities 1, 7
• In pregnant women of Mediterranean, Middle Eastern, Southeast Asian, or African ancestry with persistent mild anemia unresponsive to prenatal iron, evaluate with MCV, RDW, and hemoglobin electrophoresis to avoid missing thalassemia diagnosis 8