From the Guidelines
Alpha thalassemia trait is a genetic condition that typically requires no specific treatment, as it usually causes minimal or no symptoms, and iron supplementation should be avoided unless true iron deficiency is confirmed, as it won't improve the microcytosis and could lead to iron overload. This condition results from deletions or mutations in one or two of the four alpha-globin genes, leading to reduced alpha-globin chain production, and is characterized by microcytic erythrocytosis (small red blood cells with increased numbers) with or without mild anemia 1. The diagnosis is typically made through complete blood count showing microcytosis with normal or slightly reduced hemoglobin, normal or elevated red blood cell count, and hemoglobin electrophoresis, and molecular genetic testing can confirm the specific alpha-globin gene mutations. Some key points to consider in the management of alpha thalassemia trait include:
- Genetic counseling is recommended for family planning, as couples where both partners have alpha thalassemia trait may have children with more severe forms of the condition 1
- Patients should be educated about their carrier status and that their microcytosis is not iron deficiency, to avoid unnecessary iron therapy 1
- Serum ferritin concentration is the most powerful test for iron deficiency, and a serum ferritin concentration of <12 μg/dl is diagnostic of ID, however, serum ferritin may be raised above 12–15 μg/dl in patients with ID and concurrent chronic inflammation, malignancy, or hepatic disease 1 It is essential to integrate clinical and molecular insights into daily practice to avoid unnecessary delay in diagnosis, invasive or costly diagnostic tests, and harmful treatments, and to recognize that in some genetic anemias, such as the sideroblastic anemias, iron overload is of greater consequence than the anemia itself, and unrecognized tissue iron loading might lead to severe morbidity and even mortality 1.
From the Research
Alpha Thalassemia Trait Characteristics
- Alpha thalassemia trait is generally associated with microcytic erythrocytosis with or without mild anemia 2
- It is a group of autosomal recessive hemoglobinopathies affecting the production of normal alpha- or beta-globin chains that comprise hemoglobin 2
- Ineffective production of alpha- or beta-globin chains may result in ineffective erythropoiesis, premature red blood cell destruction, and anemia 2
Diagnosis and Differentiation
- Thalassemia should be suspected in patients with microcytic anemia and normal or elevated ferritin levels 2
- Hemoglobin electrophoresis may reveal common characteristics of different thalassemia subtypes, but genetic testing is required to confirm the diagnosis 2
- A new index, called the Matos & Carvalho Index, has been developed to discriminate between iron deficiency anemia and thalassemia trait, with good diagnostic accuracy based on parameters derived from the blood cell count 3
Clinical Presentation and Treatment
- Alpha-thalassemia major results in hydrops fetalis and is often fatal at birth 2
- Beta-thalassemia major requires lifelong transfusions starting in early childhood 2
- Treatment of thalassemia includes transfusions, iron chelation therapy, hydroxyurea, hematopoietic stem cell transplantation, and luspatercept 2
- Coexisting iron deficiency anemia and beta thalassemia trait can be treated with oral iron therapy, leading to significant improvement in hemoglobin and red cell indices 4
Specific Considerations for Alpha-Thalassemia
- Alpha-thalassemia represents a group of recessively inherited hemoglobin disorders marked by deficient or absent synthesis of 1 to all 4 of the α-globin genes 5
- Inactivation of 3 α-globin genes results in hemoglobin H (Hb H) disease, which can have moderate to severe hemolytic anemia and variable degree of ineffective erythropoiesis 5
- Treatment for deletional Hb H disease is primarily preventative and transfusions are uncommon, while patients with nondeletional Hb H disease may require regular transfusions and comprehensive care 5