ilovepathology's video: Hemolytic Anemias- Part 7: Paroxysmal nocturnal hemoglobinuria PNH

Definition: Paroxysmal nocturnal hemoglobinuria (PNH) is a disease that results from acquired mutations in the phosphatidylinositol glycan complementation group A gene (PIGA), an enzyme that is essential for the synthesis of certain membrane-associated complement regulatory protein Typical Clinical Triad: Intravascular hemolysis, Bone marrow failure, and propensity to Thromboembolism History and Epidemiology: first described in the 18th century. It is a rare disease, with a worldwide prevalence estimated in the range of 1–5 cases per million regardless of ethnicity; an increased prevalence is reported in some regions which also harbor higher incidence of aplastic anemia (eg, Thailand and some other Asian countries) Unique feature: only hemolytic anemia caused by an acquired genetic defect Pathophysiology: Somatic mutation in the Phosphatidylinositol glycan complement group A gene(PIGA gene) [Cause: PIGA is X-linked and subject to lyonization (random inactivation of one X chromosome in cells of females) leading to a single acquired mutation in the active PIGA gene of any given cell] ↓ Deficient specialized phospholipid called glycosylphosphatidylinositol (GPI) linked protein in a hematopoetic stem cell PNH blood cells are deficient in three GPI-linked proteins that regulate complement activity: (1) Decay-accelerating factor or CD55 (2) Membrane inhibitor of reactive lysis or CD59