What are the treatment options for beta (β) thalassemia?

Beta Thalassemia: Diagnosis and Treatment

Diagnosis

Beta thalassemia is diagnosed through complete blood count showing microcytic anemia, hemoglobin electrophoresis demonstrating elevated HbA2 and HbF levels, and DNA analysis to identify specific beta-globin gene mutations. 1

Diagnostic Testing

• Complete blood count reveals microcytic anemia with reduced hemoglobin levels 1
• Blood smear examination shows characteristic red blood cell abnormalities 1
• Hemoglobin electrophoresis differentiates thalassemia types and severity 1
• DNA analysis (genetic testing) identifies specific mutations in the beta-globin gene 1
• Prenatal testing through amniocentesis allows early diagnosis in at-risk pregnancies 1

Treatment Strategy

Transfusion-Dependent Thalassemia Major

Initiate 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 iron chelation therapy to prevent life-threatening cardiac complications. 2, 3

Regular Transfusion Protocol

• Start transfusions immediately when diagnosis is confirmed to raise hemoglobin above 9 g/dL 3
• Maintain pre-transfusion hemoglobin of 9-10 g/dL to balance iron loading minimization with symptom control 4, 3
• Target post-transfusion hemoglobin of 13-14 g/dL to suppress ineffective erythropoiesis 4, 3
• Transfuse every 3-4 weeks on a regular schedule 2
• This moderate transfusion regimen reduces iron loading compared to hypertransfusion while effectively suppressing erythropoiesis 5

Iron Chelation Therapy (Mandatory)

Begin iron chelation as soon as regular transfusions are established, as each unit of blood contains 200-250 mg of iron with no physiological excretion mechanism, and cardiac iron overload causes 70% of deaths in thalassemia. 6, 4

First-Line Chelation Options:

• Deferoxamine (subcutaneous): 50 mg/kg/day via subcutaneous infusion 5-7 nights per week 2

  • Highly effective but burdensome administration 2
  • Gold standard for cardiac iron removal 4

• Deferasirox (oral): Starting dose 20-30 mg/kg/day 7

  • Doses below 20 mg/kg/day fail to consistently lower liver iron concentration 7
  • Monitor renal function as it may be problematic with marginal renal perfusion 4

• Deferiprone (oral): 75 mg/kg/day 4, 3

  • Risk of neutropenia requiring weekly blood count monitoring 2, 3
  • Particularly effective for cardiac iron removal 4

Combination Therapy for Severe Cardiac Iron:

• Daily subcutaneous deferoxamine PLUS daily oral deferiprone (both drugs taken together every day) for patients with cardiac T2* <6 ms or impaired left ventricular function 4
• This combination is more effective than monotherapy for severe cardiac iron overload 4

Monitoring Requirements

Cardiac Surveillance (Critical)

• Annual cardiac MRI T2* to detect cardiac iron before symptoms develop 2, 3
  • T2* <20 ms indicates cardiac iron loading 4
  • T2* <10 ms requires intensified chelation 4
  • T2* <6 ms carries 47% risk of heart failure within 1 year and should be treated as aggressively as overt heart failure 4
• Annual echocardiography to assess left ventricular ejection fraction 2, 3

Iron Status Monitoring

• Liver iron concentration via MRI to guide chelation intensity 3, 7
• Serum ferritin every 3 months as a trend marker 4, 3
• Target serum ferritin <1000 mcg/L for optimal outcomes 5

Endocrine and Metabolic Screening

• Annual screening for diabetes mellitus 2, 3
• Annual thyroid function tests 2, 3
• Annual assessment for hypogonadism 2, 3
• Liver function tests every 3 months 3

Infection Prevention

• Hepatitis B vaccination before starting transfusions if not previously immunized 2
• Screen for hepatitis B and C regularly, as chronic viral hepatitis is common in transfused patients 3
• Vaccinate sexual partners of HBV-positive patients 2

Dietary Modifications

• Limit red meat consumption to reduce heme iron intake which is highly absorbed 2
• Never take iron supplements or multivitamins containing iron 2
• Limit vitamin C to <500 mg daily, as excess vitamin C mobilizes iron from stores and worsens cardiac deposition 2
• Consume citrus fruits and juices alone, not with meals, to minimize iron absorption enhancement 2
• Avoid or minimize alcohol, as it accelerates liver damage in iron overload 2

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, when disease-free survival exceeds 90% with matched sibling donors. 2

• Age and iron-related organ dysfunction are the main predictors of transplant complications 2
• Gene therapy is emerging as a powerful curative approach but remains investigational 8

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, as cardiac iron-related heart failure has 50% one-year mortality if inadequately treated. 4, 3

• Obtain immediate bedside echocardiography 3
• Maintain continuous cardiac monitoring 4
• Use minimal diuretics only, as thalassemia patients require adequate preload 4, 3
• Cardiac iron removes very slowly even with intensive chelation and requires years of treatment 4

Thalassemia Intermedia

• Initially may not require transfusions 4, 6
• Monitor for complications including pulmonary hypertension and thrombosis 4
• May require transfusions later in life to prevent cardiovascular complications, which then necessitates iron chelation 4, 6

Reproductive Counseling

• Test partners for thalassemia carrier status, as two carriers have 25% chance of having a child with thalassemia major 2
• Pregnancy is possible with proper management despite potential fertility issues 2

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, 6