Wallach's Interpretation of Diagnostic Tests: Pathways to Arriving at a Clinical Diagnosis (303 page)

HEMOGLOBIN E–β-THALASSEMIA

   Definition

The most common symptomatic thalassemia in Southeast Asia. A severe condition that resembles β-thalassemia intermedia or β-thalassemia major (see below).

   Laboratory Findings

   Hemolytic anemia varies from moderate to severe, similar to β-thalassemias (see below).

   Peripheral blood smear (PBS) shows severe hypochromia and macrocytosis and marked anisopoikilocytosis with many teardrop and target red cells. Nucleated RBC and basophilic stippling may be present.

HEMOGLOBIN E–ALPHA-THALASSEMIA

A mild hemolytic anemia encountered in Southeast Asia. It causes microcytosis. The severity depends on the number of α genes deleted (see α-thalassemia below).

   
THE THALASSEMIAS

Thalassemias are chronic, microcytic, hemolytic anemias. They result from defective synthesis of either β- or α-globin subunits of the Hb A molecule. Thalassemias are classified into β- or α-thalassemia according to which of the globin chain is affected. The thalassemias are among the most common genetic disorders world-wide. They have an autosomal recessive inheritance resulting in either homozygous (thalassemia major) or subtle (thalassemia minor) clinical abnormalities. The β-thalassemia syndromes are extremely heterogenous. In addition to β-thalassemia trait and β-thalassemia major described below, there are combinations with other hemoglobinopathies and variants described above.

β-THALASSEMIA MAJOR

   Definition and Who Should Be Suspected

A severe condition resulting from impaired or absent production of the β globin chains of Hb. The resulting excess α chains precipitate inside the red cells with dire consequences: severe hemolysis, skeletal changes, liver abnormalities, premature gallbladder bilirubin stones, splenomegaly, aplastic crises, impaired growth, endocrine and cardiopulmonary complications, and hemosiderosis resulting from RBC transfusions. The clinical expression of the severe phenotype is extremely heterogenous. A milder form of β-thalassemia, b
-thalassemia intermedia
, is seen in patients with one β (−) allele mutation that produce no β globin chains and with a β (+) mutation from the second allele. It produces a small amount of β chains, thus these patients are less severely affected.

   β-thalassemia is most common in individuals of Mediterranean ancestry (mutations result from protection against endemic malaria in the Mediterranean basin); it is also found in African Americans and in some groups in India.

   Infants are well at birth, depending on high levels of HbF (no β chains, just α and fetal globins), for tissue oxygenation. The diagnosis is usually established at 6–12 months of age due to increasing symptoms: pallor, irritability, growth retardation abdominal swelling due to hepatosplenomegaly, followed by abnormal skeletal development, the result of an expanding extramedullary hematopoiesis.

   Coinheritance of an α-thalassemia trait may ameliorate the morbidity of β-thalassemia major.

   Laboratory Findings

   CBC.