Paroxysmal Nocturnal Hemoglobinuria

Abstract

Paroxysmal nocturnal hemoglobinuria (PNH) is a clonal hematopoietic disorder arising from a mutation in the X chromosome-linked PIG-A gene. The mutated cell is unable to build the GPI anchor, which is needed to bind a number of molecules on the outer cell surface. Some GPI-linked molecules are responsible for cell defense against activated complement; this is why PNH red cells are hypersensitive to complement attack and are continuously destroyed in the circulation, with paroxysmal exacerbations. However, many other defects are present on PNH cell membrane, involving red cells, granulocytes, monocytes, and platelets, leading to tendency to infection and thrombosis. This review highlights the molecular pathophysiology of the disease and analyses the mechanisms responsible for the expansion of a hematopoietic clone, which is paradoxically less vital as compared with normal cells. Key Words: Aplastic anemia; bone marrow failure; CD55/DAF; CD59/MIRL; clonal hematopoiesis; complement-mediated lysis; escape theory; GPI anchor; GPI-linked molecules; intravascular hemolysis; pancytopenia; paroxysmal nocturnal hemoglobinuria; PIG-A gene; T-cell clonality; thrombophilia.