Wallach's Interpretation of Diagnostic Tests: Pathways to Arriving at a Clinical Diagnosis (902 page)

   Interpretation

   Both the DAT and the IAT are reported and interpreted as either positive or negative.

   The DAT is positive whenever the patient’s red cells are coated with autoantibodies that developed against the patient’s own red cells. It is also positive when alloantibodies in a recipient’s circulation react with antigens on recently transfused red cells, as well as alloantibodies in maternal circulation, which cross the placenta and coat fetal red cells. Antibodies directed against certain drugs may also bind to red cell membranes and result in a positive test.

   The IAT is positive in the presence of serum alloantibodies in patients previously transfused and immunized against non-self–red cell antigens.

   Limitations

   Finding of a positive DAT indicates the presence of red cell autoantibodies, alloantibodies following transfusions, or of coating of red cells with excess immunoglobulins. It requires additional workup to elucidate the etiology of the immunoglobulins by performing tests for antibody specificity: cold agglutinins (see p. 377 under hemolytic anemias), Donath-Landsteiner antibody (see p. 379), and also serum protein electrophoresis or immunofixation when a plasmacytic disease (see p. 432) is suspected. The administration of certain drugs (α-methyldopa, IV penicillin, or procainamide) and recent transfusions must also be excluded.

   A negative DAT does not rule out hemolysis but only hemolysis of autoimmune etiology. For instance, DAT is negative in some cases of drug-induced hemolytic anemias, hemoglobinopathies, hereditary spherocytosis, and other hereditary hemolytic anemias.

   A positive IAT requires further investigation to identify more precisely the offending antigen(s).

ENZYME TESTS THAT DETECT CHOLESTASIS (ALP, 5’-NUCLEOTIDASE, GGT, LAP)

   Definition

   ALP refers to a group of enzymes that catalyze the hydrolysis of a large number of organic phosphate esters at an alkaline pH optimum. The major value of the serum ALP in the diagnosis of liver disorders is in the recognition of cholestatic disease. However, an elevation in the ALP concentration is a relatively common finding and does not always indicate the presence of hepatobiliary disease. The degree of elevation does not distinguish between intra- and extrahepatic cholestasis. Elevations in serum 5ʹ-nucleotidase are seen in the same types of hepatobiliary diseases associated with an increased serum ALP. Most studies suggest that serum ALP and 5ʹ-nucleotidase are equally valuable in demonstrating biliary obstruction or hepatic infiltrative and spaceoccupying lesions. Elevated serum levels of gamma-glutamyl transpeptidase (GGT) are found in diseases of the liver, biliary tract, and pancreas, and reflect the same spectrum of hepatobiliary disease as ALP, 5ʹ-nucleotidase, and leucine aminopeptidase. Serum GGT and ALP correlate reasonably well. There are conflicting data as to whether serum GGT has better sensitivity for hepatobiliary disease than ALP or leucine aminopeptidase.

   Interpretation