Epidemiologic Study of Transfusion-Related Alpha-Gal Syndrome

Importance: Recent case reports suggest that B antigen-containing blood products may be associated with anaphylactic transfusion reactions in recipients with preformed immunoglobulin E to galactose-α-1,3-galactose (alpha-gal). Objective: To test the association of local alpha-gal syndrome (AGS) prevalence and allergic transfusion reaction (ATR) in patients with blood type O. Design, Setting, and Participants: In this international, multicenter, retrospective cohort study at academic medical centers, sites were assigned to AGS high- or low-prevalence clusters based on the known geographic distribution of AGS. Data were collected on platelet or plasma transfusions and ATRs during 2020 to 2024. Consecutive patients receiving platelet or plasma transfusions were included. Exposures: Patients with blood type O who received B or AB units and patients with blood type O who received O units (reference group) in AGS high- and low-prevalence clusters were compared. Main Outcomes and Measures: Before data collection, the hypothesis was that if transfusion-related alpha-gal syndrome (TRAGS) is a true clinical entity, excess ATRs to group B or AB units would be detected in AGS high-prevalence regions exclusively. The main measure was the overall risk ratio (RR) for ATRs to B or AB plasma or platelets in AGS high- vs low-prevalence clusters. Results: In total, 558 823 platelet and plasma transfusions at 40 sites in 5 countries were analyzed, of which ATRs occurred in 1744 transfusions (0.3%). In the US AGS high-prevalence cluster (9 sites), significantly more ATRs of any severity occurred among patients with blood type O who received B or AB units vs patients with blood type O who received O units (overall RR, 3.93; 95% CI, 2.96-5.21; P < .001). In contrast, in the primary analysis of the AGS low-prevalence cluster (15 sites), excess ATRs to B or AB units were not detected. In subgroup analyses among patients with blood type O receiving B units, the RR for moderate to severe ATRs was 9.14 (95% CI, 5.39-15.52; P < .001) in the AGS high-prevalence cluster vs 2.15 (95% CI, 1.34-3.47; P = .002) in the AGS low-prevalence cluster. Outside the US, a signal consistent with TRAGS was not detected. Conclusions and Relevance: This cohort study provides provocative epidemiologic evidence that TRAGS may be a unique manifestation of AGS and a previously unrecognized risk associated with transfusion. In AGS high-prevalence regions, blood collectors and hospital transfusion services should consider approaches to preventing severe ATRs from B or AB plasma or platelet units.

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Journal
JAMA Internal Medicine
Published
2026-08-24
DOI
https://doi.org/10.1001/jamainternmed.2026.3983
Primary Topic
Blood groups and transfusion
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article
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article

Epidemiologic Study of Transfusion-Related Alpha-Gal Syndrome

Nancy M. Dunbar, Wen Lu, Catherine Humbrecht, Jensyn Cone Sullivan et al.
JAMA Internal Medicine
Blood groups and transfusion
article

Epidemiologic Study of Transfusion-Related Alpha-Gal Syndrome

Nancy M. Dunbar, Wen Lu, Catherine Humbrecht, Jensyn Cone Sullivan, Pierre Tiberghien, Carlo Brugnara, Konstanze Aurich, Minoko Takanashi, Valeria De Giorgi, Allison Mo, Suzanne R. Thibodeaux, Claudia S. Cohn, Erica M. Wood, Richard Schäfer, Robertson D. Davenport, Keenan Hogan, Scott P. Commins, Kamille West-Mitchell, Jun Yamanouchi, Clara C. Cousins, Jessica Poisson, Regina M. DelBaugh, Cyril Jacquot, Anna C. Nelson, Colleen W. Gilstad, Ryan A. Metcalf, Monica B. Pagano, Elizabeth S. Allen, Yasuyuki Arai, Mark A Cervinski, Yoshinori Takeda, Jennifer Andrews, Nikitha Samy, Ayda Javanbakht, Anne G. Hoen, Andres E. Mindiola Romero, Jeanne E. Hendrickson, Nabiha H. Saifee, Elizabeth P. Crowe, Jay S. Raval, Jenna Khan, Georgia Mills, Richard M. Kaufman, Sajjad Afraz, Alexander Gofton, Sheryl van Nunen, Kate Hill, Simon J. Stanworth, Marie C. Pauly, Maureen J. Miller, John Casey, Satoshi Yoshihara, Mrigender S. Virk, Tomohiko Sato, UPTICK Study Group; for the Biomedical Excellence for Safer Transfusion (BEST) Collaborative, Monique M. Menzies Wojtowicz, C. Michael Knudson, Alyssa Ziman, Rebecca Cardigan, Meghan Delaney, X. Long Zheng, Kazuhiko Ikeda, Emily A. Scherer, Justin E Juskewitch
article en

Abstract

Importance: Recent case reports suggest that B antigen-containing blood products may be associated with anaphylactic transfusion reactions in recipients with preformed immunoglobulin E to galactose-α-1,3-galactose (alpha-gal). Objective: To test the association of local alpha-gal syndrome (AGS) prevalence and allergic transfusion reaction (ATR) in patients with blood type O. Design, Setting, and Participants: In this international, multicenter, retrospective cohort study at academic medical centers, sites were assigned to AGS high- or low-prevalence clusters based on the known geographic distribution of AGS. Data were collected on platelet or plasma transfusions and ATRs during 2020 to 2024. Consecutive patients receiving platelet or plasma transfusions were included. Exposures: Patients with blood type O who received B or AB units and patients with blood type O who received O units (reference group) in AGS high- and low-prevalence clusters were compared. Main Outcomes and Measures: Before data collection, the hypothesis was that if transfusion-related alpha-gal syndrome (TRAGS) is a true clinical entity, excess ATRs to group B or AB units would be detected in AGS high-prevalence regions exclusively. The main measure was the overall risk ratio (RR) for ATRs to B or AB plasma or platelets in AGS high- vs low-prevalence clusters. Results: In total, 558 823 platelet and plasma transfusions at 40 sites in 5 countries were analyzed, of which ATRs occurred in 1744 transfusions (0.3%). In the US AGS high-prevalence cluster (9 sites), significantly more ATRs of any severity occurred among patients with blood type O who received B or AB units vs patients with blood type O who received O units (overall RR, 3.93; 95% CI, 2.96-5.21; P < .001). In contrast, in the primary analysis of the AGS low-prevalence cluster (15 sites), excess ATRs to B or AB units were not detected. In subgroup analyses among patients with blood type O receiving B units, the RR for moderate to severe ATRs was 9.14 (95% CI, 5.39-15.52; P < .001) in the AGS high-prevalence cluster vs 2.15 (95% CI, 1.34-3.47; P = .002) in the AGS low-prevalence cluster. Outside the US, a signal consistent with TRAGS was not detected. Conclusions and Relevance: This cohort study provides provocative epidemiologic evidence that TRAGS may be a unique manifestation of AGS and a previously unrecognized risk associated with transfusion. In AGS high-prevalence regions, blood collectors and hospital transfusion services should consider approaches to preventing severe ATRs from B or AB plasma or platelet units.

JAMA Internal Medicine
Dartmouth College (US), University of Vermont (US), Dartmouth–Hitchcock Medical Center (US), Commonwealth Scientific and Industrial Research Organisation (AU), Seattle Children's Hospital (US), National Institutes of Health (US), Fukushima Medical University (JP), Emory Healthcare (US), Mayo Clinic (US), Children's National (US), Johns Hopkins University (US), University of California, Los Angeles (US), University of New Mexico (US), Duke University (US), Georgetown University (US), Virginia Commonwealth University (US), Australian Red Cross Lifeblood (AU), University of Washington (US), Washington University in St. Louis (US), University of Missouri–St. Louis (US), University of Utah (US), University of Michigan (US), Universitätsmedizin Greifswald (DE), University of Virginia Health System (US), Johns Hopkins Medicine (US), University of Minnesota System (US), Gosford Hospital (AU), University Medical Center Freiburg (DE), Princess Alexandra Hospital (AU), MedStar Georgetown University Hospital (US), University of California San Diego (US), Japanese Red Cross College of Nursing (JP), Japanese Red Cross Medical Center (JP), The Jikei University Hospital (JP), Collaborative Group (United States) (US), University of Kansas Medical Center (US), Établissement Français du Sang (FR), University of Iowa Health Care (US), Ehime University (JP), Université Marie et Louis Pasteur (FR), Monash University (AU), Seattle University (US), Hyogo University (JP), The University of Texas Southwestern Medical Center (US), Vanderbilt University Medical Center (US), Université de Franche-Comté (FR), Stanford University (US), Macquarie University (AU)
Good health and well-being
Openalex Percentile: Top 10%
Blood groups and transfusion
DOISourceOpenAlex
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