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Mechanism of intravascular hemolysis in paroxysmal nocturnal hemoglobinuria (PNH)
Author(s) -
Nakakuma Hideki
Publication year - 1996
Publication title -
american journal of hematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.456
H-Index - 105
eISSN - 1096-8652
pISSN - 0361-8609
DOI - 10.1002/(sici)1096-8652(199609)53:1<22::aid-ajh5>3.0.co;2-7
Subject(s) - paroxysmal nocturnal hemoglobinuria , hemolysis , cd59 , complement system , hemoglobinuria , pathophysiology , complement membrane attack complex , eculizumab , immunology , mechanism (biology) , biology , microbiology and biotechnology , endocrinology , immune system , philosophy , epistemology
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 N ‐acetylglucosamine 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? © 1996 Wiley‐Liss, Inc.