ICCS/ESCCA consensus guidelines to detect GPI-deficient cells in paroxysmal nocturnal hemoglobinuria (PNH) and related disorders part 1 – clinical utility

Paroxysmal nocturnal hemoglobinuria (PNH) arises as a consequence of the non-malignant clonal expansion of one or more hematopoietic stem cells with an acquired somatic mutation of the PIGA gene (Brodsky RA. Blood 113 (2009) 6522–6527). Progeny of affected stem cells are deficient in glycosyl phosphatidylinositol–anchored proteins (GPI-APs). This deficiency is readily detected by flow cytometry. Though this seems straightforward, the clinical utility of this testing requires that the ordering clinician understand not only the characteristics of the test, but also the biology of the underlying disease, and the clinical and laboratory manifestations in the individual patient. When interpreted correctly, the results from PNH flow cytometry testing, including presence and size of the clonal populations and the cell types involved, can allow the clinician to classify the disease appropriately; evaluate the risk of disease progression; and subsequently monitor response to therapy. In these guidelines, we discuss the evaluation of a patient with suspected PNH or other bone marrow failure disorders, with specific emphasis on the contribution of this testing to the diagnosis, classification, and monitoring of patients. For convenience we will commonly refer to these flow cytometry studies as “PNH testing” recognizing that an abnormal result is not diagnostic of PNH; rather both laboratory and clinical features are used to establish this diagnosis.