What is the recommended evaluation and treatment approach for an adult with beta thalassemia, including assessment of transfusion dependence, iron overload management, organ monitoring, and curative options such as hematopoietic stem‑cell transplantation or gene therapy?

Management of Beta Thalassemia in Adults

Adults with beta thalassemia require regular transfusions every 3-4 weeks to maintain pre-transfusion hemoglobin at 9-10 g/dL, immediate initiation of iron chelation therapy once regular transfusions begin, and annual cardiac MRI T2 surveillance to prevent cardiac iron overload—the leading cause of death accounting for 70% of mortality in these patients.* 1, 2

Transfusion Strategy

Establish a fixed transfusion schedule every 3-4 weeks to maintain pre-transfusion hemoglobin between 9-10 g/dL and achieve post-transfusion levels of 13-14 g/dL. 1 This aggressive transfusion approach suppresses ineffective erythropoiesis and prevents skeletal deformities that occur with inadequate transfusion. 1

• Patients requiring more than 8 transfusion events per year meet criteria for transfusion-dependent thalassemia major. 1
• Each unit of packed red blood cells contains 200-250 mg of elemental iron that accumulates with no physiological excretion mechanism. 1, 2
• Monitor hemoglobin levels every 2 weeks, particularly if concurrent antiviral treatment is needed. 1

Iron Chelation Therapy

Initiate iron chelation immediately once regular transfusions are established—do not wait. 1 The traditional threshold of serum ferritin >1000 ng/mL after approximately 20-25 units should not delay chelation in transfusion-dependent patients, as cardiac iron overload is the primary cause of death. 1

Chelator Selection for Cardiac Iron

The evidence on chelator efficacy for cardiac iron removal shows important differences: 3

• Deferiprone is superior to deferoxamine for removing cardiac iron without overt cardiac dysfunction. 3
• Combined deferiprone plus deferoxamine is superior to deferoxamine alone for cardiac iron removal. 3
• Deferasirox is equivalent to deferoxamine for cardiac iron removal. 3

Critical Pitfall: Ferritin Limitations

Do not rely on single ferritin measurements to guide chelation decisions. 1 Inflammation falsely elevates ferritin independent of iron stores, particularly in patients with hepatitis C. 1 More importantly, ferritin does not predict cardiac iron loading, which is the leading cause of death in thalassemia. 1

Organ Surveillance Protocol

Cardiac Monitoring (Highest Priority)

Perform annual echocardiography and cardiac MRI T2 to detect early iron-related cardiomyopathy before symptoms develop.* 1 Cardiac complications account for approximately 70% of deaths in transfusion-dependent thalassemia patients. 2, 4

• If cardiac complications are suspected, obtain immediate bedside echocardiography to exclude acute decompensated heart failure—this is a medical emergency where delay can be life-threatening. 1
• Transfer to a specialized thalassemia center with integrated cardiology and hematology expertise if cardiac complications are present. 1
• Avoid aggressive diuretic therapy as thalassemia patients require adequate preload; use minimal diuretics only. 1

Hepatic Monitoring

• Liver function tests every 3 months to monitor for hepatotoxicity from iron overload or chelation therapy. 1
• Screen for hepatitis B and C at baseline and periodically, as chronic viral hepatitis affects many adult thalassemia patients. 1
• Patients with HBV or HCV and cirrhosis require liver ultrasound every 6 months for hepatocellular carcinoma surveillance, as they are at 6-fold higher risk. 1

Endocrine Surveillance

Annual screening for diabetes, thyroid dysfunction, and hypogonadism is mandatory, as iron deposition causes widespread subclinical organ dysfunction including glucose intolerance with reduced insulin output and limited pituitary reserves. 1

Management of Concurrent Viral Hepatitis

For HCV infection, use combination therapy with pegylated interferon plus ribavirin for 24 weeks (genotypes 2/3) or 48 weeks (genotypes 1/4). 1

Critical adjustments during antiviral therapy: 1

• Anticipate a 30-40% increase in transfusion requirements due to ribavirin-induced hemolysis
• Switch to deferoxamine during antiviral treatment to avoid compounding neutropenia risk with deferiprone
• Exclude patients with decompensated myocardiopathy or severe arrhythmias from antiviral therapy

Curative Treatment Options

Hematopoietic stem cell transplantation (HSCT) is the only currently available cure for thalassemia major, with disease-free survival around 80% and overall survival over 90%. 1

• For patients with an HLA-identical sibling donor or well-matched related or unrelated donor, HSCT should be performed as soon as possible to avoid transfusion-associated complications. 1
• Optimize iron chelation before bone marrow transplant to reduce non-relapse mortality, as effective iron chelation therapy prevents the impact of iron overload on non-relapse mortality in transfusion-dependent thalassemia patients undergoing allo-SCT. 1

Thalassemia Intermedia Considerations

Thalassemia intermedia patients generally do not require transfusions initially but may need them later in life to prevent complications. 3, 5 When transfusions begin in adulthood, these patients are at very high risk for developing red cell alloimmunization and serious hemolytic transfusion reactions. 6

• These patients develop iron overload primarily through increased gastrointestinal iron absorption due to ineffective erythropoiesis, even without transfusions. 2
• Cardiovascular manifestations typically include greater propensity to pulmonary hypertension and thrombosis compared to thalassemia major. 3

Expected Outcomes

With optimal adherence to transfusions and chelation, survival into the fourth or fifth decade is now achievable for thalassemia major patients, whereas without treatment, death typically occurs by age 10 from cardiac complications. 1, 2 Before the introduction of chelation therapy, patients with transfused but unchelated β-thalassemia typically died by age 10, primarily from cardiac complications. 2