What is the management and treatment of beta thalassemia?

Management and Treatment of Beta Thalassemia

Core Treatment Strategy

Beta thalassemia requires regular blood transfusions every 3-4 weeks maintaining 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. 1, 2

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Transfusion Protocol

Initiation and Targets

• Begin regular transfusions immediately when diagnosis is confirmed in transfusion-dependent patients to maintain hemoglobin above 9 g/dL 2, 3
• Transfuse every 3-4 weeks on a fixed schedule to suppress ineffective erythropoiesis and reduce cardiac stress from chronic anemia 1, 2
• Target pre-transfusion hemoglobin of 9-10 g/dL to balance minimizing iron loading while controlling symptoms 1, 2
• Target post-transfusion hemoglobin of 13-14 g/dL to adequately suppress ineffective erythropoiesis 1, 2, 3

Monitoring During Transfusions

• Monitor hemoglobin levels every 2 weeks, especially during concurrent antiviral treatment if needed 3
• Screen for hepatitis B and C at baseline and regularly, as chronic viral hepatitis is common in transfused patients 1, 2, 3
• Vaccinate against hepatitis B before starting transfusions if not previously immunized 2

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Iron Chelation Therapy

When to Start

Begin iron chelation immediately when 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. 1, 2

First-Line Chelation Options

Deferoxamine (subcutaneous):

• Dose: 50 mg/kg/day via subcutaneous infusion 5-7 nights per week 1, 2
• Strength of evidence: High 2

Deferiprone (oral):

• Dose: 75 mg/kg/day orally 1, 2
• Strength of evidence: Moderate 2
• Use with caution due to neutropenia risk, particularly avoid during concurrent antiviral therapy 3

Deferasirox (oral):

• Starting dose: 20-30 mg/kg/day based on liver iron concentration 1
• Doses below 20 mg/kg/day fail to provide consistent lowering of liver iron concentration and serum ferritin 4
• Target serum ferritin <1000 mcg/L, though MRI is more accurate than ferritin alone 3

Combination Chelation for Cardiac Emergency

If acute heart failure develops, immediately initiate continuous intravenous deferoxamine 50 mg/kg/day PLUS oral deferiprone 75 mg/kg/day and transfer to a specialized thalassemia center. 2, 3

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Monitoring Requirements

Cardiac Surveillance

• Cardiac MRI T2 annually* to detect cardiac iron before symptoms develop (strength of evidence: high) 1, 2, 3
• Echocardiography annually to assess left ventricular ejection fraction (strength of evidence: moderate) 1, 2, 3
• Maintain continuous electrocardiographic and hemodynamic monitoring if cardiac complications are present 3

Iron Monitoring

• Serum ferritin every 3 months as a trend marker (strength of evidence: low) 1, 2
• Liver iron concentration (LIC) via MRI to guide chelation therapy intensity 1, 3
• Liver function tests every 3 months 3

Endocrine Surveillance

• Annual screening for diabetes, thyroid dysfunction, and hypogonadism 3

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Dietary Modifications

• Limit red meat consumption to reduce heme iron intake, which is highly absorbed 2
• Never take iron supplements or multivitamins containing iron (strength of evidence: high) 2

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Management of Hepatitis Co-infection

Hepatitis C

• Use Peg-interferon plus ribavirin for 24 weeks (genotypes 2/3) or 48 weeks (genotypes 1/4) 1, 3
• Anticipate a 30-40% increase in transfusion requirements during antiviral therapy due to ribavirin-induced hemolysis 1, 3
• Switch to deferoxamine during antiviral treatment to avoid neutropenia risk with deferiprone 3
• Exclude patients with decompensated myocardiopathy or severe arrhythmias from antiviral therapy 3

Hepatitis B

• Consider Peg-interferon or nucleoside/nucleotide analogs (NUCs) based on HBeAg status 3

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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 (strength of evidence: high). 1, 2, 5, 6

• Optimize iron chelation before bone marrow transplant to reduce non-relapse mortality 3
• HSCT is limited by clinical conditions, availability of matched donors, and potential graft-versus-host disease 7

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Management of Acute Cardiac Decompensation

Emergency Protocol

• Obtain immediate bedside echocardiography to exclude acute decompensated heart failure, as cardiac iron overload can present with seizures and has 50% one-year mortality if untreated 3
• Transfer immediately to a specialized thalassemia center with integrated cardiology and hematology expertise 3
• Initiate continuous intravenous deferoxamine 50 mg/kg/day PLUS oral deferiprone 75 mg/kg/day for combined chelation 2, 3
• Avoid aggressive diuretic therapy as thalassemia patients require adequate preload; use minimal diuretics only 3

Seizure Management

• Avoid valproic acid if possible due to potential hepatotoxicity in patients with underlying liver disease from iron overload or viral hepatitis 3
• Do not delay cardiac assessment thinking seizures are purely neurological 3

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Special Considerations for E Beta Thalassemia

• E beta thalassemia patients demonstrate greater propensity for pulmonary hypertension and thrombosis compared to beta thalassemia major 1
• Management follows the same transfusion-dependent protocol, with some patients classified as thalassemia intermedia (non-transfusion-dependent) requiring individualized approaches 1

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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 (strength of evidence: high). 2

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Common Pitfalls to Avoid

• Do not use deferasirox doses below 20 mg/kg/day, as they fail to consistently lower liver iron concentration 4
• Do not use deferiprone during concurrent antiviral therapy due to increased neutropenia risk 3
• Do not rely on serum ferritin alone for iron monitoring; MRI is more accurate 3
• Do not underestimate transfusion requirements during antiviral therapy, which increase by 30-40% 1, 3
• Do not delay cardiac assessment in patients presenting with seizures, as cardiac iron overload can present this way 3