Paroxysmal nocturnal hemoglobinuria — pathophysiology, classification and modern diagnostics

Abstract

Paroxysmal nocturnal hemoglobinuria (PNH) is a rare acquired clonal hematopoietic stem cell di- sease due to the somatic mutation of the PIGA gene. As a result, the clonal expansion of cells with­out glycosylphosphatidylinositol molecules (PNH clone) is observed which is associated with the lack of several proteins of different functions, including complement inhibitors CD55 and CD59. The deficiency of these proteins on erythrocyte surface is the main factor of the pathogenesis of PNH. In patients with PNH a triad of symptoms, expressed in varying degrees is observed, including hemolysis, thrombotic disorders and bone marrow failure. PNH is currently classified, taking into account clinical symptoms and the size of the defect into three groups: classical PNH, PNH clone accompanying marrow failure, and subclinical form of PNH. Modern diagnostic methods based on the flow cytometry analysis, using monoclonal antibodies, as well as FLAER reagent is essential for the detection and monitoring of PNH clone size, which has an important practical significance.