title: Complement in hemolytic anemia.
abstract: Complement is increasingly being recognized as an important driver of human disease, including many hemolytic anemias. Paroxysmal nocturnal hemoglobinuria (PNH) cells are susceptible to hemolysis because of a loss of the complement regulatory proteins CD59 and CD55. Patients with atypical hemolytic uremic syndrome (aHUS) develop a thrombotic microangiopathy (TMA) that in most cases is attributable to mutations that lead to activation of the alternative pathway of complement. For optimal therapy, it is critical, but often difficult, to distinguish aHUS from other TMAs, such as thrombotic thrombocytopenic purpura; however, novel bioassays are being developed. In cold agglutinin disease (CAD), immunoglobulin M autoantibodies fix complement on the surface of red cells, resulting in extravascular hemolysis by the reticuloendothelial system. Drugs that inhibit complement activation are increasingly being used to treat these diseases. This article discusses the pathophysiology, diagnosis, and therapy for PNH, aHUS, and CAD.
authors.affiliation: Division of Hematology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD.
authors.forename: Robert A
authors.initials: RA
authors.lastname: Brodsky
mesh_terms: D000818:Animals; D065766:Atypical Hemolytic Uremic Syndrome / Q000097:blood* / Q000188:drug therapy; D018958:CD55 Antigens / Q000097:blood*; D018957:CD59 Antigens / Q000097:blood*; D003167:Complement Activation; D003165:Complement System Proteins / Q000378:metabolism*; D006457:Hemoglobinuria, Paroxysmal / Q000097:blood* / Q000188:drug therapy; D006801:Humans; D057049:Thrombotic Microangiopathies / Q000097:blood / Q000188:drug therapy
chemical_list: D018958:CD55 Antigens; D018957:CD59 Antigens; C051590:CD59 protein, human; D003165:Complement System Proteins