PATHOGENESIS AND EPIDEMIOLOGY OF IG PRODUCT-RELATED HEMOLYSIS
Pathogenesis and mechanisms of antibody-mediated hemolysis
Willy A. Flegel,
Corresponding Author
Willy A. Flegel
Department of Transfusion Medicine, NIH Clinical Center, National Institutes of Health, Bethesda, Maryland
Address reprint requests to: Willy A. Flegel, MD, Department of Transfusion Medicine, NIH Clinical Center, National Institutes of Health, Bethesda, MD 20892; e-mail: [email protected].Search for more papers by this authorWilly A. Flegel,
Corresponding Author
Willy A. Flegel
Department of Transfusion Medicine, NIH Clinical Center, National Institutes of Health, Bethesda, Maryland
Address reprint requests to: Willy A. Flegel, MD, Department of Transfusion Medicine, NIH Clinical Center, National Institutes of Health, Bethesda, MD 20892; e-mail: [email protected].Search for more papers by this authorThis work was supported by the Intramural Research Program of the NIH Clinical Center.
The views expressed do not necessarily represent the view of the National Institutes of Health, the Department of Health and Human Services, or the U.S. Federal Government.
This manuscript represents the author's thoughts on the subject and his interpretation of a set of slides prepared by Dr George Garratty (Slide Set S1, available as supporting information in the online version of this paper) as presented in the transcript of the Strategies to Address Hemolytic Complications of Immune Globulin Infusions Workshop organized by FDA/PPTA/NHLBI in Bethesda on January 28, 2014.
Abstract
BACKGROUND
The clinical consequences of antibodies to red blood cells (RBCs) have been studied for a century. Most clinically relevant antibodies can be detected by sensitive in vitro assays. Several mechanisms of antibody-mediated hemolysis are well understood. Such hemolysis after transfusion is reliably avoided in a donor-recipient pair, if one individual is negative for the cognate antigen to which the other has the antibody.
STUDY DESIGN AND RESULTS
Mechanisms of antibody-mediated hemolysis were reviewed based on a presentation at the Strategies to Address Hemolytic Complications of Immune Globulin Infusions Workshop addressing intravenous immunoglobulin (IVIG) and ABO antibodies. The presented topics included the rates of intravascular and extravascular hemolysis; immunoglobulin (Ig)M and IgG isoagglutinins; auto- and alloantibodies; antibody specificity; A, B, A,B, and A1 antigens; A1 versus A2 phenotypes; monocytes-macrophages, other immune cells, and complement; monocyte monolayer assay; antibody-dependent cell-mediated cytotoxicity; and transfusion reactions due to ABO and other antibodies.
CONCLUSION
Several clinically relevant questions remained unresolved, and diagnostic tools were lacking to routinely and reliably predict the clinical consequences of RBC antibodies. Most hemolytic transfusion reactions associated with IVIG were due to ABO antibodies. Reducing the titers of such antibodies in IVIG may lower the frequency of this kind of adverse event. The only way to stop these events is to have no anti-A or anti-B in the IVIG products.
Supporting Information
Additional Supporting Information may be found in the online version of this article at the publisher's website:
| Filename | Description |
|---|---|
| trf13147-sup-0001-suppinfo.pdf4.7 MB |
Slide Set S1. George Garratty: Pathogenesis and mechanisms of immune hemolytic anemia. January 2014. |
Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
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