Paroxysmal nocturnal hemoglobinuria (PNH) is a disorder characterized by a defect in the glycosylphosphatidylinositol (GPI) anchor, due to an acquired abnormality in the PIG-A gene. This leads to partial or complete absence of all GPI-linked proteins, particularly CD59 (membrane inhibitor of reactive lysis) and CD55 (decay accelerating factor), resulting in an increased sensitivity of the affected cells to the action of complement . (See "Pathogenesis of paroxysmal nocturnal hemoglobinuria".)
The clinical manifestations of PNH are primarily related to abnormalities in the hematopoietic system, including hemolytic anemia, a hypercoagulable state, and diminished hematopoiesis. Progression to aplastic anemia, myelodysplasia, and acute leukemia can also occur. In the past, the treatment of PNH had been largely empirical. As with most medical disorders, therapy is largely given to ameliorate the symptoms or complications rather than the cause of the disease. However, with improved understanding of the underlying pathogenesis, more rational therapies are emerging, such as the use of eculizumab. (See 'Eculizumab' below.)
The diagnosis and treatment of PNH will be reviewed here [1-4]. The clinical manifestations of this disorder are discussed separately. (See "Clinical manifestations of paroxysmal nocturnal hemoglobinuria".)
Clinical presentation of the classic disease — The diagnosis of PNH should be considered in a patient with any of the following manifestations:
●Evidence of acquired hemolysis, specifically with a negative direct antiglobulin (Coombs) test of the red cells.