Wallach's Interpretation of Diagnostic Tests: Pathways to Arriving at a Clinical Diagnosis (313 page)

   Patients with unexplained refractory anemia.

   Laboratory Findings

Highly Recommended

   Flow cytometry (high sensitivity and specificity).

   At least two different monoclonal antibodies, directed against two different glycosylphosphatidylinositol (GPI) anchored proteins, either absent or greatly diminished in PNH, on at least two different cell lineages, should be used to diagnose a patient with PNH. In fact, the preferred approach includes the detailed evaluation of leukocytes, because some red blood cells may be lost secondary to hemolysis or diluted from their true frequency by repeated transfusions.

   CD59 and CD55 are the most commonly assessed. Other monoclonal antibodies directed against determinants on leukocytes such as CD14, CD16, and CD24, can be used.

   Fluorescently labeled aerolysin (FLAER): This reagent is more sensitive and specific than the available monoclonal antibodies. This allows the simultaneous detection of PNH clones in monocyte and neutrophil lineages in a single-tube, multiparameter flow cytometric assay.

   Direct Coombs test: negative.

Recommended

   CBC: RBC indices: macrocytic anemia evolving into a microcytic picture. Reticulocytes are increased, but not commensurate with the degree of anemia. Mild leukopenia and thrombocytopenia may be present; if severe, a combination with aplastic anemia or another bone marrow failure syndrome should be considered.

   Bone marrow: normoblastic hyperplasia; indicated if an additional underlying hematologic disease is suspected.

   Haptoglobin: reduced.

   Serum iron and ferritin: decreased.

   Karyotype: normal.

   LDH: increased.