Exploring the frontiers of IVIG-associated hemolysis

Authors:  Jacob Pendergrast, B.A., B.Sc., MD, FRCPC; Donald Branch, B.Sc., MT (ASCP), PhD


Red blood cell hemolysis following administration of intravenous immunoglobulin (IVIG) can occur in individuals of blood group A, B and AB due to the ABO isoagglutinins (anti-A and anti-B) contained in all IVIG products. The risk of hemolysis in non-blood group O people is related to the dose of IVIG given, with the risk becoming significant when given at immunomodulatory doses (e.g., ≥2 g/kg.) Although it has been reported that hemolysis resulting from IVIG administration occurs in about 35–37% of non-O patients receiving these high doses, with about 10% of the cases being severe and sometimes life-threatening, many clinicians are not aware of this adverse effect, in part because the onset is usually delayed by 5-10 days after the IVIG has been administered. Indeed, until recently, no studies have prospectively looked at the mechanism and incidence of IVIG-associated hemolysis; however, efforts to minimize the potential for IVIG products to cause hemolysis have begun, with manufacturers reducing the ABO isoagglutinins in newer formulations of IVIG. These research gaps are addressed in this educational symposium.

In this educational symposium organized by the Canadian Society for Transfusion Medicine and CSL Behring, Dr. Pendergrast and Dr. Branch present the incidence and risk factors for IVIG-associated hemolysis and explore new advances in the prevention and minimization of IVIG-associated hemolysis.

Dr. Pendergrast’s presentation highlights the prevalence and incidence of IVIG-associated hemolysis, the role of isoagglutinin binding density and macrophage function, and patient risk factors.

Dr. Branch’s presentation focuses on the research between isoagglutinin-reduced versus non-reduced IVIG, highlighting the differences in anti-A and anti-B titers, and proposing impact of isoagglutinin-reduced IVIG on hemolytic adverse events in patients requiring high-dose IVIG therapy.

This symposium was recorded on May 29, 2020 and edited for posting on this website.

To view an unabridged recording of the symposium, visit the Canadian Society for Transfusion Medicine website.


The Canadian Society for Transfusion Medicine is an inter-professional organization that promotes excellence in transfusion medicine for Canadians. The vision of the Society is to inspire and promote safe transfusion practices, to promote quality and provide guidance for hospital transfusion services, to facilitate opportunities for education and research in transfusion medicine, to cultivate regional, national, and international partnerships with key stakeholders. To learn more about The Canadian Society for Transfusion Medicine visit Transfusion.ca.