Study: Non-O Blood Type Transfusions, Higher Intravenous Immunoglobulin Lead to Increased Risk of Hemolytic Reactions


Although the patient demographics are similar for the 3 categories of hemolytic reactions with intravenous immunoglobulin, the reaction with delayed hemolytic transfusion reactions was highest compared to the other 2 hemolytic reactions.

Hemolytic reactions with intravenous immunoglobulin (IVIG) infusions have decreased over time, with risk factors including non-O blood group transfusions and IVIG dosage, according to results of a study published in Vox Sanguinis.1

man in hospital having an intravenous drip immunoglobulin infusion

Image credit: UlrikaArt -

Investigators question whether medication taken prior to the procedure may increase the risk of hemolysis. In a study previously published in Transfusion, investigators reported that in 33 articles, there was a higher incidence of IVIG-related hemolysis in patients with blood groups A and AB and for those who had higher IVIG doses, which supports the findings of the current study.2

In the current study, the authors said that hemolysis can occur after an IVIG infusion. According to the investigators, hemolytic reactions are the fourth most common reaction to IVIG. Out of 1170 reactions included in the study, the most common reactions were febrile non-hemolytic reactions (26.1%), minor allergic reactions (24.5%), IVIG headache (15.3%), and hemolytic reactions (10.3%).1

They analyzed data using a novel approach, including 2 control groups with no hemolysis in reaction to IVIG. Investigators included a summary of all reactions to IVIG, rate estimates, and analysis of hemolytic reactions, which included risk factors.1

The study authors gathered data from Ontario, Canada from 2013 to 2021. The data included IVIG distribution, transfusion data from the blood supplier, and data from a large local transfusion registry. Investigators had a control group of patients who had IVIG reactions that were not hemolytic and a control group of patients who had no adverse reactions to IVIG. A descriptive analysis and 2 logistic regression models were used for the different control groups, according to the study authors.1

Investigators noted that the current estimate of reaction times from 2020 were 1.5/1000 kg IVIG use and 2.9/1000 kg IVIG use, respectively.1

The results of the study showed that the 2 biggest risk factors for hemolysis were receiving a non-O blood type transfusion and IVIG dose per 10 g increase. The risk factors were also evident when compared to the results of the no-reaction control group.1

Furthermore, investigators found that no pre-medication was associated with a higher risk of hemolysis.1

Although the patient demographics were similar for the 3 categories of hemolytic reactions, the rate of delayed hemolytic transfusion reactions (DHTR) was highest compared to acute hemolytic transfusion reactions and delayed serological transfusion reactions. Investigators reported that most of the reactions were classified as non-severe, while 41.9% were classified as severe and 4.7% were life threatening. The severe reactions were most frequent with DHTR, according to the study authors.1

The study authors identified various limitations of the study, which include limitations regarding data from surveillance. They identified that the structure of the reporting form could have led to missing data, a failure to report key test results that could indicate types of reactions, and a lack of diagnosis or other clinical data, including the reason for transfusion.1

Investigators said their results confirm previous studies indicating risk factors for hemolysis with IVIG, but also suggest that the lack of pre-medication could be another risk factor. They said the methodology in their study could be applied to other studies, investigating other types of rations following transfusions.1


  1. Batarfi K, Liu Y, Nixon J, Webert KE, et al. A retrospective analysis of haemolytic reactions to intravenous immunoglobulin using data from the Transfusion-Transmitted Injuries Surveillance System (Ontario). Vox Sang. 2023;10.1111/vox.13501. doi:10.1111/vox.13501
  2. Cuesta H, El Menyawi I, Hubsch A, Hoefferer L, et al. Incidence and risk factors for intravenous immunoglobulin-related hemolysis: A systematic review of clinical trial and real-world populations. Transfusion. 2022;62(9):1894-1907. doi:10.1111/trf.17028
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