From the Guidelines
Thalassemia major patients should receive lifelong iron chelation treatment to prevent or reverse iron-related complications, in addition to regular blood transfusions, as this approach has been shown to improve morbidity, mortality, and quality of life outcomes. Thalassemia is an inherited blood disorder characterized by reduced or abnormal production of hemoglobin, leading to anemia. It occurs when there are mutations in genes responsible for hemoglobin production, with two main types: alpha and beta thalassemia, depending on which part of the hemoglobin molecule is affected. Treatment varies based on severity, with mild forms often requiring no intervention beyond periodic monitoring. Moderate to severe cases may need regular blood transfusions every 2-4 weeks to maintain adequate hemoglobin levels, typically aiming for hemoglobin levels of 9-10 g/dL.
Key Considerations
- Iron chelation therapy is essential for transfusion-dependent patients, using medications like deferasirox (Exjade, 20-40 mg/kg/day), deferiprone (Ferriprox, 75-100 mg/kg/day in three divided doses), or deferoxamine (Desferal, 20-60 mg/kg/day via subcutaneous infusion) to prevent iron overload complications, as supported by the American Heart Association consensus statement 1.
- Bone marrow transplantation offers a potential cure but carries risks and requires a compatible donor, with current experience worldwide showing that more than 90% of patients now survive hematopoietic stem cell transplantation and disease-free survival is around 80% 1.
- Folic acid supplementation (1 mg daily) helps support red blood cell production.
- The disorder results from impaired synthesis of either alpha or beta globin chains, creating an imbalance that causes premature destruction of red blood cells and ineffective erythropoiesis.
Management
- Regular monitoring of hemoglobin levels, iron status, and organ function is crucial for managing this lifelong condition effectively.
- A broad phenotypic characterization of thalassemia major is the requirement for >8 transfusion events per year in an adult aged >16 years, as noted in the Circulation journal study 1.
From the Research
Overview of Thalassemia
- Thalassemia is a group of autosomal recessive hemoglobinopathies affecting the production of normal alpha- or beta-globin chains that comprise hemoglobin 2.
- It is a global disease that is most highly prevalent in Southeast Asia, Africa, and Mediterranean countries, but its distribution is changing due to population migration 3.
Types and Symptoms of Thalassemia
- Thalassemia should be suspected in patients with microcytic anemia and normal or elevated ferritin levels 2.
- Alpha-thalassemia major results in hydrops fetalis and is often fatal at birth, while beta-thalassemia major requires lifelong transfusions starting in early childhood 2.
- Alpha- and beta-thalassemia intermedia have variable presentations based on gene mutation or deletion, with mild forms requiring only monitoring but more severe forms leading to symptomatic anemia and requiring transfusion 2.
Treatment and Management of Thalassemia
- Treatment of thalassemia includes transfusions, iron chelation therapy to correct iron overload, hydroxyurea, hematopoietic stem cell transplantation, and luspatercept 2, 4.
- Iron chelation therapy is essential to prevent cardiac failure and other complications due to iron accumulation 3, 5.
- The safety of licensed drugs for the management of beta-thalassemia is reviewed, using evidence from clinical trials and observational research 6.
Complications and Quality of Life
- Thalassemia complications arise from bone marrow expansion, extramedullary hematopoiesis, and iron deposition in peripheral tissues, affecting the skeletal system, endocrine organs, heart, and liver 2.
- Life expectancy of those with thalassemia has improved dramatically over the past 50 years with increased availability of blood transfusions and iron chelation therapy, and improved iron overload monitoring 2, 5.
- Advances in the understanding of the pathology of beta-thalassemia have led to the development of new treatment options that have the potential to reduce the RBC transfusion burden in patients with transfusion-dependent beta-thalassemia and improve quality of life 4.