Paroxysmal nocturnal hemoglobinuria

Paroxysmal nocturnal hemoglobinuria is a rare acquired blood disorder caused by PIGA-mutant blood-forming stem cells. Their descendants lack complement-protective surface proteins, leading to blood-cell destruction, thrombosis, and sometimes bone marrow failure.

PIGA: PIGA is a gene required for the first step in assembling glycosylphosphatidylinositol anchors. Acquired mutations in this gene give rise to the abnormal blood-cell clone.
Flow cytometry: Flow cytometry measures properties of individual cells as they pass through a laser-equipped instrument. It detects and quantifies blood cells lacking GPI-linked proteins in suspected PNH.
Thrombosis: Thrombosis is the formation of a blood clot within a blood vessel. Clots are a major cause of serious illness and death in PNH.
Autoimmune hemolytic anemia: Autoimmune hemolytic anemia is red-cell destruction caused by antibodies directed against the body's own red cells. Unlike PNH, its red-cell injury is antibody-mediated rather than due to missing GPI-linked complement regulators.
Glycosylphosphatidylinositol anchor: A glycolipid structure that attaches certain proteins to the outer surface of a cell membrane. PNH cells lack these anchors, so they cannot display key complement regulators.
FLAER: FLAER is a fluorescent aerolysin reagent that binds glycosylphosphatidylinositol anchors on blood cells. Its failure to bind identifies GPI-anchor-deficient leukocytes in PNH testing.
Cerebral venous sinus thrombosis: Cerebral venous sinus thrombosis is a clot in the veins that drain blood from the brain. It is one of the unusual-site clots associated with PNH.
Hereditary spherocytosis: Hereditary spherocytosis is an inherited red-cell membrane disorder that causes spherical cells and hemolytic anemia. It causes hemolysis through an inherited membrane defect, not an acquired complement-sensitive clone.
CD55: CD55 is a cell-surface protein that accelerates the decay of complement convertases. Its absence leaves PNH red cells more vulnerable to complement-mediated lysis.
Eculizumab: Eculizumab is a monoclonal antibody that blocks complement protein C5. C5 inhibition reduces intravascular hemolysis and thrombosis in PNH.

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