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Thalassemia: causes, symptoms, diagnosis, treatment
Last reviewed: 05.07.2025
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Thalassemia (hereditary leptocytosis, Mediterranean anemia, major and minor thalassemia) is a group of hereditary microcytic hemolytic anemias characterized by anomaly of hemoglobin synthesis. They are especially typical for people of Mediterranean, African, Asian origin. Symptoms and complaints are caused by the development of anemia, hemolysis, splenomegaly, bone marrow hyperplasia and, with multiple transfusions, iron overload. Diagnosis is based on quantitative hemoglobin analysis. Treatment of severe forms includes blood transfusions, splenectomy, chelation therapy, stem cell transplantation.
Causes thalassemias
Thalassemia (hemoglobinopathy-b) is the most common inherited disorder of hemoglobin synthesis. The result of unbalanced hemoglobin synthesis is a violation of the production of at least one polypeptide chain (b a in 5).
Beta-thalassemia is the result of a disorder in the synthesis of beta-polypeptide chains. The inheritance pattern is autosomal, heterozygous patients are carriers and have asymptomatic anemia of mild to moderate severity (thalassemia minor), while the homozygous form (major beta-thalassemia or Cooley's anemia) develops severe anemia with bone marrow hyperplasia.
Beta thalassemia is the result of decreased synthesis of the beta polypeptide chain, has more complex congenital anomalies, since the control of synthesis
Beta chains are expressed by 2 pairs of genes (4 genes). The heterozygous form with one genetic defect [beta-thalassemia-2 (latent)] is usually asymptomatic. The heterozygous form with defects in 2 of 4 genes [beta-thalassemia-1 (typical)] results in mild to moderate asymptomatic microcytic anemia. Abnormalities in 3 of 4 genes impair beta chain production to a greater extent, resulting in the formation of tetramers with excess beta-chains (HbH) or, in children, y-chains (Barts' Hb). Abnormalities in 4 genes are lethal in utero; Hb lacking the beta-chain is unable to transport O 2. In blacks, the incidence of beta-thalassemia is about 25%, but only 10% have abnormalities in more than 2 genes.
Symptoms thalassemias
The clinical features of thalassemia are similar but vary in severity. β-thalassemia major presents at 1 to 2 years of age with features of severe anemia, post-transfusion and absorption iron overload. Patients have jaundice, leg ulcers, and cholelithiasis (as in sickle cell anemia). Massive splenomegaly is typical. Sequestration of red blood cells in the spleen may develop, increasing the destruction of transfused normal red blood cells. Bone marrow hyperplasia causes thickening of the skull and malar prominences. Involvement of the tubular bones predisposes to pathological fractures, growth failure, and possibly delayed sexual development. Accumulation of iron in the myocardium may lead to heart failure. Hepatic hemosiderosis is typical, leading to liver dysfunction and cirrhosis. Patients with HbH often have symptoms of hemolytic anemia and splenomegaly.
Diagnostics thalassemias
Thalassemia is suspected in patients with a family history, characteristic symptoms and signs of microcytic hemolytic anemia. If thalassemia is suspected, the studies recommended for microcytic and hemolytic anemias with quantitative determination of Hb are performed. There is an increase in serum bilirubin, iron and ferritin levels.
In major beta-thalassemia, severe anemia is detected, often with hemoglobin less than 60 g/l. The number of red blood cells is increased compared to the hemoglobin level, since there is pronounced microcytosis of the cells. In the peripheral blood smear, changes characteristic of this diagnosis are determined: a large number of nucleated red blood cells, target cells, small, pale red blood cells, basophilic puncturation.
Quantitative hemoglobin testing reveals elevated HbA, which is typical of beta-thalassemia minor. In beta-thalassemia major, the HbF level is usually elevated, sometimes up to 90%, and HbA is usually elevated by more than 3%. In beta-thalassemia, the percentage of HbF and HbA is usually within normal limits, and the detection of one or two genetic abnormalities typical of thalassemia excludes other causes of microcytic anemia. HbH disease can be diagnosed by detecting HbH or the Barts fraction during hemoglobin electrophoresis. Specific molecular changes can be identified, but this does not change the clinical management of the patient. Gene mapping is performed for prenatal diagnosis and genetic counseling.
If a bone marrow examination is performed (e.g., to exclude other causes), the myelogram will show erythroid hyperplasia. Radiography in patients with beta-thalassemia major shows changes due to chronic bone marrow hyperplasia. Skull radiographs show cortical thinning, widening of the diplopic spaces with a sunburst pattern, and the appearance of granules or ground glass. Tubular bones may have cortical thinning, widening of the bone marrow spaces, and foci of osteoporosis. Vertebral bodies may show granules or ground glass. Finger joints may be convex or rectangular.
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Treatment thalassemias
Patients with beta- and beta-thalassemia minor do not require treatment. Splenomegaly may be effective in patients with HbH disease in the presence of severe anemia or splenomegaly.
Children with beta-thalassemia major should receive as few transfusions as possible to prevent iron overload. However, suppression of abnormal hematopoiesis using periodic red blood cell transfusions may be effective in patients with severe disease. Excess (transfusion) iron should be removed (eg, by chelation therapy) to prevent or reduce hemochromatosis. Splenectomy may reduce the need for transfusion therapy in patients with splenomegaly. Allogeneic stem cell transplantation may be effective but requires a histocompatible donor, and the risk of complications, including death, and the need for long-term immunosuppressive therapy limit its use.