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For further information, see CMDT Part 15-04: The Thalassemias
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Essentials of Diagnosis
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Microcytosis out of proportion to degree of anemia
Positive family history or lifelong personal history of microcytic anemia
Normal or elevated red blood cell (RBC) count
Abnormal RBC morphology with microcytes, hypochromia, acanthocytes, and target cells
In β-thalassemia, elevated levels of hemoglobin A2 or F
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General Considerations
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Hereditary disorder of several types characterized by reduction in synthesis of globin chains (α or β), causing reduced hemoglobin synthesis and eventually hypochromic microcytic anemia
Normal adult hemoglobin is primarily hemoglobin A, a tetramer of two α-chains and two β-chains (α2β2)
Thalassemias are described as
Trait, when there are laboratory features without clinical impact
Intermedia, when there is an RBC transfusion requirement or other moderate clinical impact
Major, when the disorder is life-threatening
α-Thalassemia syndromes are determined by the number of functional α-globin genes
Normal (four α-globin genes, normal hematocrit)
Silent carrier (three α-globin genes, normal hematocrit)
α-Thalassemia minor or trait (two α-globin genes, hematocrit 28–40%, mean cell volume [MCV] 60–75 fL)
Hemoglobin H disease (one α-globin gene, hematocrit 22–32%, MCV 60–70 fL)
Hydrops fetalis (0 α-globin genes, fatal in utero)
β-Thalassemia: Reduced β-globin chain synthesis results in relative increase in proportions of hemoglobins A2 and F compared with hemoglobin A, because β-like globins (δ and γ) substitute for missing β-chains
With reduced β-chains
Excess α-chains precipitate, causing hemolysis
Bone marrow becomes hyperplastic, resulting in bony deformities, osteopenia, and pathologic fractures, as well as extramedullary hematopoiesis
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α-Thalassemia occurs primarily in persons from southeast Asia and China and, less commonly, in Black persons and persons of Mediterranean origin (eg, Italian, Greek)
β-Thalassemia affects persons of Mediterranean origin (eg, Italian, Greek) and to lesser extent Asian and Black persons
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α-Thalassemia silent carriers: asymptomatic
α-Thalassemia trait: clinically normal with mild microcytic anemia
Hemoglobin H disease
Hydrops fetalis
Only hemoglobin species made is called hemoglobin Bart's (γ4)
All four α-globin genes are deleted, no normal hemoglobin is produced and the affected fetus is stillborn
Heterozygotes for β-thalassemia (thalassemia minor): mild microcytic anemia
Homozygotes for mild β-thalassemia (thalassemia intermedia): chronic hemolytic anemia
Homozygotes for major β-thalassemia (thalassemia major)
Severe anemia requiring transfusion
Growth failure
Bony deformities (abnormal facial structure, pathologic bone fractures)
Hepatosplenomegaly and jaundice
Thrombophilia
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Differential Diagnosis
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Iron deficiency anemia (thalassemia has lower MCV, normal iron studies, more normal RBC count, more abnormal peripheral blood smear at modest levels of anemia, and usually reticulocytosis)
Other hemoglobinopathy (eg, sickle thalassemia, hemoglobin C disorders)
Sideroblastic anemia
Anemia of chronic disease