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a phenotypic switch in myeloproliferative neoplasms,

More severe thalassemias are suspected in patients with a family history, suggestive symptoms or signs, or microcytic hemolytic anemia. If thalassemias are suspected, laboratory tests for microcytic and hemolytic anemias and quantitative hemoglobin studies are done. Serum bilirubin, iron, and ferritin levels are increased.

In alpha-thalassemias, the percentages of Hb F and Hb A2 are generally normal, and the diagnosis of single or double gene defect thalassemias may be carried out with newer genetic tests. The diagnosis often is one of exclusion of other causes of microcytic anemia.

In beta-thalassemia major, anemia is severe, often with hemoglobin ≤ 6 g/dL (≤ 60 g/L). Red blood cell count is elevated relative to hemoglobin because the cells are very microcytic. The blood smear is virtually diagnostic, with many nucleated erythroblasts; target cells; small, pale red blood cells; and punctate and diffuse basophilia.

In quantitative hemoglobin studies, elevation of Hb A2 is diagnostic for beta-thalassemia minor. In beta-thalassemia major, Hb F is usually increased, sometimes to as much as 90%, and Hb A2 is usually elevated to > 3%.

Hb H disease can be diagnosed by demonstrating the fast-migrating Hb H or Bart’s fractions on hemoglobin electrophoresis. The specific molecular defect can be characterized but does not alter the clinical approach.

Recombinant DNA approaches of gene mapping (particularly polymerase chain reaction [PCR]) have become standard for prenatal diagnosis and genetic counseling.

If bone marrow examination is done for anemia (eg, to exclude other causes), it shows marked erythroid hyperplasia. X-rays done for other reasons in patients with beta-thalassemia major show changes due to chronic bone marrow hyperactivity. The skull may show cortical thinning, widened diploic space, a sun-ray appearance of the trabeculae, and a granular or ground-glass appearance. The long bones may show cortical thinning, marrow space widening, and areas of osteoporosis. The vertebral bodies may have a granular or ground-glass appearance. The phalanges may appear rectangular or biconvex.