Wallach's Interpretation of Diagnostic Tests: Pathways to Arriving at a Clinical Diagnosis (305 page)

   Haptoglobin is decreased.

   Endocrine abnormalities are related to extensive iron deposits, with laboratory evidence of hypogonadism and diabetes.

   Hypercoagulability: abnormalities in the level of clotting factors and their inhibitors have been reported in some cases.

β-THALASSEMIA MINOR (TRAIT)

   Definition

Heterozygotes who carry one normal β-globin allele and one β-thalassemic allele are clinically normal but have an abnormal hematologic picture that may mislead for a diagnosis of iron deficiency.

   Laboratory Findings

   CBC shows microcytic anemia. The anemia is milder (Hg 10–13 g/dL), but the microcytosis is more profound (MCV 60–70 fL) than seen in iron deficiency. RBC count may be higher than normal (another contrast to iron deficiency anemia). RDW is normal, since the RBCs are uniformly microcytic and hypochromic. On peripheral blood smear (PBS), basophilic stippling of RBCs and target cells may be observed. During pregnancy, carriers may develop a more profound anemia, than attributable to the physiologic anemia of pregnancy.

   Hb variant analysis: HbA2 is elevated, sometimes as high as 7–8% with the ratio HbA2/HbA1 being 1:20 instead of the normal 1:40; HgF is slightly elevated in 50% of cases. Some forms of β-thalassemia trait may have a normal concentration of HbA2. Definitive diagnosis can only made by molecular genetic techniques.

ALPHA-THALASSEMIA SYNDROMES

   Definition

Normal subjects have four α globin genes, two on each chromosome. The α-thalassemias are caused by mutations or deletions affecting the production of one or more of the four α globin genes. This defect results in a relative excess of β globin chains, which may lead to hemolysis.

   Who Should Be Suspected?

α-Thalassemia should be suspected based on a family history of anemia and geographic and ethnic background. The condition is prevalent in populations of African, Middle East, or Southeast Asian ancestry. The diagnosis is further suspected in cases of microcytic, hypochromic anemia not due to iron deficiency, with normal levels of HbA
₂
on hemoglobin variant analysis.

   Diagnosis

The severity of the syndrome depends on the number of α genes affected.

   Loss of all four α globin loci results in
hydrops fetalis with Hb Bart
, condi tion incompatible with extrauterine life. This condition is not seen in populations of African ancestry, but it is encountered in Asian populations. Hb Bart is composed of four γ globin chains, which fails to deliver oxygen to tissues. It is fast moving on Hb electrophoresis.

   Loss of three α loci results in
Hemoglobin H disease
. These patients have a moderate microcytic, hypochromic anemia with inclusion bodies present on the peripheral blood smear (PBS). Hb levels are usually 8–10 g/dL. Hb electrophoresis or chromatographic techniques show 5–30% HbH, which is the result of tetrameric β-chains. HbH disease can be acquired in hematologic malignancies, especially in myelodysplastic syndromes.