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For further information, see CMDT Part 13-04: 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 beta-thalassemia, elevated levels of hemoglobin A2 and F
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General Considerations
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Hereditary disorders characterized by reduction in synthesis of globin chains (alpha or β), causing reduced hemoglobin synthesis and eventually hypochromic microcytic anemia
Normal adult hemoglobin is primarily hemoglobin A, a tetramer of two alpha-chains and two beta-chains (alpha2beta2)
Thalassemias are described as
Trait, when there are laboratory features without clinical impact
Intermedia, when there is a RBC transfusion requirement or other moderate clinical impact
Major, when the disorder is life-threatening
Alpha-thalassemia syndromes are determined by the number of functional alpha-globin genes
Normal (four alpha-globin genes, normal hematocrit)
Silent carrier (three alpha-globin genes, normal hematocrit)
Alpha-thalassemia minor or trait (two alpha-globin genes, hematocrit 28–40%, mean cell volume [MCV] 60–75 fL)
Hemoglobin H disease (one alpha-globin gene, hematocrit 22–32%, MCV 60–70 fL)
Hydrops fetalis (0 alpha-globin genes, fatal in utero)
Beta-thalassemia: Reduced beta-globin chain synthesis results in relative increase in proportions of hemoglobins A2 and F compared with hemoglobin A, because beta-like globins (delta and gamma) substitute for missing beta-chains
With reduced beta-chains
Excess alpha-chains precipitate, causing hemolysis
Bone marrow becomes hyperplastic, resulting in bony deformities, osteopenia, and pathologic fractures
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Alpha-thalassemia occurs primarily in persons from southeast Asia and China and, less commonly, in blacks and persons of Mediterranean origin
Beta-thalassemia affects persons of Mediterranean origin (Italian, Greek) and to lesser extent Asians and blacks
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Alpha-thalassemia silent carriers: asymptomatic
Alpha-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 alpha-globin genes are deleted, no normal hemoglobin is produced and the affected fetus is stillborn
Heterozygotes for beta-thalassemia (thalassemia minor): mild microcytic anemia
Homozygotes for mild beta-thalassemia (thalassemia intermedia): chronic hemolytic anemia
Homozygotes for major beta-thalassemia (thalassemia major)
Severe anemia requiring transfusion
Growth failure
Bony deformities (abnormal facial structure, pathologic bone fractures)
Hepatosplenomegaly and jaundice
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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
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Alpha-thalassemia trait
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