Paroxysmal Nocturnal Hemoglobinuria :Predisposing factor for Leukemia

The term "nocturnal" refers to the belief that hemolysis is triggered by acidosis during sleep and activates complement to hemolyze an unprotected and abnormal RBC membrane. However, this observation was later disproved. Hemolysis has been shown to occur throughout the day and is not actually paroxysmal, but the urine concentrated overnight produces the dramatic change in color.

This disease has been referred to as the great impersonator because of the variety of symptoms observed during the initial manifestation and course of paroxysmal nocturnal hemoglobinuria (PNH). The clinical syndrome can present in 3 types of symptoms including (1) an acquired intracorpuscular hemolytic anemia due to the abnormal susceptibility of the RBC membrane to the hemolytic activity of complement; (2) thromboses in large vessels, such as hepatic, abdominal, cerebral, and subdermal veins; and (3) a deficiency in hematopoiesis that may be mild or severe, such as pancytopenia in an aplastic anemia state. The triad of hemolytic anemia, pancytopenia, and thrombosis makes paroxysmal nocturnal hemoglobinuria (PNH) a truly unique clinical syndrome.Paroxysmal nocturnal hemoglobinuria (PNH) has been reclassified from purely an acquired hemolytic anemia due to a hematopoietic stem cell mutation defect. This change in concept was brought about by the observation that surface proteins were missing not only in the RBC membrane but also in all blood cells, including the platelet and white cells.Paroxysmal nocturnal hemoglobinuria (PNH) has been reclassified from purely an acquired hemolytic anemia due to a hematopoietic stem cell mutation defect. This change in concept was brought about by the observation that surface proteins were missing not only in the RBC membrane but also in all blood cells, including the platelet and white cells.The common denominator in the disease, a biochemical defect, appears to be a genetic mutation leading to the inability to synthesize the glycosyl-phosphatidylinositol (GPI) anchor that binds these proteins to cell membranes.