Complement in hemolytic anemia

• Published in: Blood Vol. 126; no. 22; pp. 2459 - 2465
• Main Author: Brodsky, Robert A.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 26-11-2015; The American Society of Hematology
• Subjects: Animals; Atypical Hemolytic Uremic Syndrome - blood; Atypical Hemolytic Uremic Syndrome - drug therapy; CD55 Antigens - blood; CD59 Antigens - blood; Complement Activation; Complement System Proteins - metabolism; Hemoglobinuria, Paroxysmal - blood; Hemoglobinuria, Paroxysmal - drug therapy; Humans; Review; Thrombotic Microangiopathies - blood; Thrombotic Microangiopathies - drug therapy
• ISSN: 0006-4971; 1528-0020; 1528-0020
• DOI: 10.1182/blood-2015-06-640995

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.