TRANSFUSION MEDICINE AND IMMUNOHEMATOLOGY: Edited by Karina YazdanbakhshRole of complement in alloimmunization and hyperhemolysisChonat, Satheesha,b; Mener, Amandac,d; Verkerke, Hansc,d; Stowell, Sean R.c,d,eAuthor Information aDepartment of Pediatrics, Emory University School of Medicine bAflac Cancer and Blood Disorders Center, Children's Healthcare of Atlanta cDepartment of Laboratory Medicine and Pathology, Center for Transfusion Medicine and Cellular Therapies dDepartment of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, Georgia eJoint Program in Transfusion Medicine, Department of Pathology, Harvard Medical School, Boston, MA, USA Correspondence to Sean R. Stowell, MD, PhD, Joint Program in Transfusion Medicine, Department of Pathology, Harvard Medical School, 630D New Research Building, 77 Avenue Louis Pasteur, Boston, MA 02115. E-mail: [email protected] Current Opinion in Hematology: November 2020 - Volume 27 - Issue 6 - p 406-414 doi: 10.1097/MOH.0000000000000610 Buy Metrics Abstract Purpose of review The purpose of this review is to summarize the role of complement in regulating the removal of a target alloantigen following an incompatible red blood cell (RBC) transfusion, the formation of alloantibodies following RBC alloantigen exposure, and the development of hyperhemolysis in patients with sickle cell disease (SCD). Recent findings Recent studies demonstrate that complement can accelerate alloantibody-mediated removal of target alloantigens from the RBC surface following incompatible transfusion. Complement also influences alloantigen availability during developing alloimmune responses and serves as a unique mediator of CD4 T-cell-independent alloantibody formation following RBC alloantigen exposure. Finally, alternative complement pathway activation appears to play a key role in the development of acute hemolytic episodes in patients with SCD, providing a potential druggable target to prevent acute complications in patients with this disease. Summary Recent studies suggest that complement can regulate a wide variety of processes germane to hematology, from transfusion complications to baseline hemolysis in patients with SCD. As the role of complement in various disease processes becomes more fully understood, the ability to leverage recently developed complement modulating drugs will only continue to enhance providers’ ability to favorably intervene in many hematological diseases. Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.