Application of flow cytometry to the diagnosis of paroxysmal nocturnal hemoglobinuria

Within the contemporary multitude of complex methods used in clinical flow cytometry, very few techniques exist which can he described as disease-spec ific diagnostic tests. Detection of glycophosphatidylinositol (GPI)-linked antigens on hematopoietic cells using monoclonal antibodies and flow cytome try forms the basis of a specific diagnostic test for paroxysmal nocturnal hemoglobinuria (PNH), Absent or markedly diminished expression of GPI-linke d antigens is, in the appropriate clinical setting, specific for all patien ts with PNH, Clinically, PNH is a syndrome characterized by bone marrow fai lure, acquired hemolytic anemia, and a thrombotic tendency. The molecular g enetic lesion responsible for this condition is a somatic mutation of the X -linked pig-a gene within a multipotent hematopoietic stem cell. Due to its rarity, delay in diagnosis is not uncommon for patients with PNH, Once a d efinitive diagnosis is established, this can make a considerable impact on patient management and prognosis. In this article, we review the compliment ary roles that molecular biology and flow cytometry have played in unraveli ng the genotypic and phenotypic aspects of this unique condition. Cytometry (Comm. Clin, Cytometry) 42:223-233, 2000, (C) 2000 Wiley-Liss, Inc.