Mechanism of intravascular hemolysis in paroxysmal nocturnal hemoglobinuria (PNH)

✍ Scribed by Nakakuma, Hideki

• Publisher: John Wiley and Sons
• Year: 1996
• Tongue: English
• Weight: 832 KB
• Volume: 53
• Category: Article
• ISSN: 0361-8609
• DOI: 10.1002/(sici)1096-8652(199609)53:1<22::aid-ajh5>3.0.co;2-7

✦ Synopsis

Paroxysmal nocturnal hemoglobinuria (PNH) hemolysis requires both intravascular complement activation and affected erythrocytes susceptible to complement. This susceptibility is explained by a deficiency in complement regulatory membrane proteins that are attached to the membrane by a glycosylphosphatidylinositol (GPI) anchor. Affected cells lack a series of GPI-anchored membrane proteins with various functions. The lack is caused by a synthetic defect of the anchor due to an impaired transfer of Kacetylglucosamine to phosphatidylinositol which is an early metabolic precursor in the anchor synthesis. Moreover, PIG-A gene responsible for the membrane defect was recently cloned. Further, a possible mechanism of complement activation has been proposed, especially for an infection-induced hemolytic precipitation which is clinically crucial. Thus, the molecular events, leading to intravascular hemolysis characteristic of PNH, has been virtually clarified. Next major concern is the nature of PIG-A: How does PIG-A explain the complex pathophysiology of PNH which exhibits various clinical manifestations?