Paroxysmal nocturnal hemoglobinuria is an acquired hematopoietic stem cell disorder. The most common clinical manifestations of PNH include intravascular hemolysis, venous thrombosis, and bone marrow failure. Hematopoietic stems cells with mutant PIG-A are present in normal marrow, but they are not noticed because they have no advantage under normal circumstances. In the setting of immune-mediated bone marrow injury, such as that seen in aplastic anemia, PIG-A mutant cells are selected because they have a survival advantage based on deficiency of one or more GPI-anchored proteins. Expansion of the PIG-A-mutant clones occurs when other events that enhance the growth properties of the cells work together with the effects of the PIG-A mutation to enhance further the growth properties of the mutant cells.