Table of Contents Author Guidelines Submit a Manuscript
BioMed Research International
Volume 2015, Article ID 363278, 11 pages
Review Article

Red Blood Cell Destruction in Autoimmune Hemolytic Anemia: Role of Complement and Potential New Targets for Therapy

1Department of Medicine, Haugesund Hospital, Helse Fonna, P.O. Box 2170, 5504 Haugesund, Norway
2Department of Immunology and Transfusion Medicine, Haugesund Hospital, Helse Fonna, P.O. Box 2170, 5504 Haugesund, Norway

Received 25 June 2014; Revised 6 November 2014; Accepted 10 November 2014

Academic Editor: Jerome Moreaux

Copyright © 2015 Sigbjørn Berentsen and Tatjana Sundic. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Autoimmune hemolytic anemia (AIHA) is a collective term for several diseases characterized by autoantibody-initiated destruction of red blood cells (RBCs). Exact subclassification is essential. We provide a review of the respective types of AIHA with emphasis on mechanisms of RBC destruction, focusing in particular on complement involvement. Complement activation plays a definitive but limited role in warm-antibody AIHA (w-AIHA), whereas primary cold agglutinin disease (CAD), secondary cold agglutinin syndrome (CAS), and paroxysmal cold hemoglobinuria (PCH) are entirely complement-dependent disorders. The details of complement involvement differ among these subtypes. The theoretical background for therapeutic complement inhibition in selected patients is very strong in CAD, CAS, and PCH but more limited in w-AIHA. The optimal target complement component for inhibition is assumed to be important and highly dependent on the type of AIHA. Complement modulation is currently not an evidence-based therapy modality in any AIHA, but a number of experimental and preclinical studies are in progress and a few clinical observations have been reported. Clinical studies of new complement inhibitors are probably not far ahead.