Thalassemia

General Principles

Definition

The thalassemia syndromes are inherited disorders characterized by reduced Hgb synthesis associated with mutations in either the α- or β-gene of the molecule (Table 21-3).

Table 21-3: Thalassemias

GenotypeHemoglobin (g/dL)Mean Cellular Volume (fL)Transfusion Dependent
α-Thalassemia
Silent carrierαα/α−NormalNoneNo
Traitα−/α− or αα/−−>10<80No
Hemoglobin Hα−/−−7–10<70±
Hydrops fetalis−−/−−Incompatible with life

β-Thalassemia (Thal)
Silent carrierβ/β+>10<80No
β-Thal minor (trait)β/β0>10<80No
β-Thal intermediaβ+/β+7–1065–75±
β-Thal majorβ+/β0 or β0/β0<7<70Yes

β+, β-thalassemia genes produce some β-globin chains but with impaired synthesis; β0, β-thalassemia genes produce no β-globin chains.

Etiology

  • β-Thalassemia results in a decreased production of β-globin and a resultant excess of α-globin, forming insoluble α-tetramers and leading to ineffective erythropoiesis.
    • β-Thalassemia minor (trait) occurs with one gene abnormality with underproduction of β-chain globin. Patients are asymptomatic and present with microcytic, hypochromic RBCs and Hgb levels >10 g/dL.
    • β-Thalassemia intermedia (non–transfusion-dependent) occurs with dysfunction in both β-globin genes so that anemia is more severe (Hgb 7–10 g/dL).
    • β-Thalassemia major (Cooley anemia or transfusion-dependent) is caused by mutations of both β globin genes that fail to produce significant amounts of β-globin and generally require lifelong RBC transfusion support.
  • α-Thalassemia occurs with a deletion of one or more of the four α-globin genes, leading to a β-globin excess.
    • Mild microcytosis and mild hypochromic anemia (Hgb >10 g/dL) are seen with the loss of one or two α-globin genes (silent carrier and α-thal trait).
    • Deletion of three α-globin genes (Hgb H disease) results in splenomegaly and hemolytic anemia. In patients with Hgb H disease, transfusion or splenectomy is often not necessary until after the second or third decade of life. In addition, oxidant drugs similar to those that exacerbate glucose-6-phosphate dehydrogenase (G6PD) deficiency should be avoided because increased hemolysis may occur.
    • Hydrops fetalis occurs with the loss of all four α-globin genes and is incompatible with life.

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