title: Paroxysmal nocturnal hemoglobinuria: a complement-mediated hemolytic anemia.
abstract: Paroxysmal nocturnal hemoglobinuria is manifests with a chronic hemolytic anemia from uncontrolled complement activation, a propensity for thrombosis and marrow failure. The hemolysis is largely mediated by the alternative pathway of complement. Clinical manifestations result from the lack of specific cell surface proteins, CD55 and CD59, on PNH cells. Complement inhibition by eculizumab leads to dramatic clinical improvement. While this therapeutic approach is effective, there is residual complement activity resulting from specific clinical scenarios as well as from upstream complement components that can account for suboptimal responses in some patients. Complement inhibition strategies are an area of active research.
authors.affiliation: Division of Hematologic Malignancies, Department of Oncology, The Bunting and Blaustein Cancer Research Building, 1650 Orleans Street, Room 3M87, Baltimore, MD 21287-0013, USA. Electronic address: adezern1@jhmi.edu.
authors.forename: Amy E
authors.initials: AE
authors.lastname: DeZern
authors.affiliation: Division of Hematology, The Johns Hopkins University School of Medicine, 720 Rutland Avenue, Ross Research Building, Room 1025, Baltimore, MD 21205, USA.
authors.forename: Robert A
authors.initials: RA
authors.lastname: Brodsky
mesh_terms: D000743:Anemia, Hemolytic / Q000276:immunology*; D061067:Antibodies, Monoclonal, Humanized / Q000276:immunology / Q000627:therapeutic use; D018958:CD55 Antigens / Q000276:immunology / Q000378:metabolism; D018957:CD59 Antigens / Q000276:immunology / Q000378:metabolism; D003167:Complement Activation / Q000187:drug effects / Q000276:immunology*; D003165:Complement System Proteins / Q000276:immunology*; D006457:Hemoglobinuria, Paroxysmal / Q000276:immunology* / Q000378:metabolism / Q000517:prevention & control; D006801:Humans; D018448:Models, Immunological
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D018958:CD55 Antigens; D018957:CD59 Antigens; D003165:Complement System Proteins; C481642:eculizumab
keywords: Alternative pathway of complement; Bone marrow failure; C1 inhibition; C3 blockade; Eculizumab; Hemolytic anemia; Humanized anti-C5 monoclonal antibody; Paroxysmal nocturnal hemoglobinuria