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Lessons learned from mouse models of hemolytic transfusion reactions

Hod, Eldad Aa; Zimring, James Cb; Spitalnik, Steven La

doi: 10.1097/MOH.0b013e328311f40a
Transfusion medicine and immunohematology: Edited by Martin L. Olsson
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Purpose of review Hemolytic transfusion reactions (HTRs) are potentially fatal complications of blood transfusions. Many studies, primarily performed in vitro, have provided a great deal of insight into the initiating events of HTRs; however, it is not clear how they are modulated and how they combine to lead to one or more of the final common pathways. Recently developed mouse HTR models now make it possible to enhance our understanding of the pathogenesis of HTRs; this will allow for the rational design of specific therapies to prevent or ameliorate this serious complication in transfusion medicine.

Recent findings Mouse models support the hypothesis that ‘cytokine storm’ plays an important role in the pathogenesis of HTRs. Nitric oxide and endothelial cell dysfunction are also implicated in the pathophysiology of these reactions. In addition, the intriguing phenomenon of ‘antigen loss,’ in which antigen crosslinking by alloantibody leads to antigen removal rather than red blood cell clearance, has been modeled and explored. Finally, these mouse models were used to evaluate new therapeutic targets employing complement receptor 1 peptide homologues and the antimacrophage agent, liposomal clodronate.

Summary Models of HTRs are valuable for gaining a better understanding of the pathophysiology of these potentially fatal complications of blood transfusion. The participation of various inflammatory mediators was shown to play a role in these reactions in vivo. This knowledge will lead to novel treatment options.

aDepartment of Pathology and Cell Biology, Columbia University Medical Center, New York, New York

bCenter for Transfusion and Cellular Therapies, Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, Georgia, USA

Correspondence to Steven L. Spitalnik, MD, Department of Pathology and Cell Biology, 630 West 168th Street, College of Physicians and Surgeons of Columbia University, New York, NY 10023, USA Tel: +1 212 305 2204; fax: +1 212 305 3693; e-mail: ss2479@columbia.edu

© 2008 Lippincott Williams & Wilkins, Inc.