Advances in pathogenesis, diagnosis and treatment of paroxysmal nocturnal hemoglobinuria

Paroxysmal nocturnal hemoglobinuria (PNH) is a rare disorder of hematopoietic stem cells due to acquisition of somatic mutations. Somatic mutations in phosphatidylinositol glycan class A (PIGA) account for intravascular hemolysis and other PNH manifestations, but the pathophysiology of clonal expansion of PNH cells cannot be elucidated clearly. PNH is closely related to aplastic anemia and myelodysplastic syndromes. Today, the gold standard for PNH is flow cytometry to detect the absence or severe deficiency of glycosylphosphatidylinositol (GPI)-anchored proteins on white and red blood cells. However, PNH diagnosed by phenotype is a group of heterogeneous disease in pathogenesis. Eculizumab, a first-in-class monoclonal antibody that inhibits terminal complement, is highly effective in stopping intravascular hemolysis and improving quality of life. Further research on the pathogenesis of PNH would be helpful to understand the underlying reasons for PNH phenotype cells in different patients, improve differential diagnosis and more targeted and specific therapy. Research progress in recent years will be reviewed in this article. Key words: Paroxysmal nocturnal hemoglobinuria; Phosphatidylinositol glycan class A; Glycosylphosphatidylinositol-anchored proteins; Clonal expansion; Eculizumab