Epidemiologic Study of Transfusion-Related Alpha-Gal Syndrome
Year: 2026
Type: article
Study design: Observational Study
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.
Source: JAMA Internal Medicine
Authors: Richard M. Kaufman, Anne G. Hoen, Jenna Khan, C. Michael Knudson, Ryan A. Metcalf, Andres E. Mindiola Romero, Allison Mo, Richard Schäfer, Minoko Takanashi, Nancy M. Dunbar, UPTICK Study Group; for the Biomedical Excellence for Safer Transfusion (BEST) Collaborative, Rebecca Cardigan, Simon J. Stanworth, Scott P. Commins, Emily A. Scherer, Mark A. Cervinski, Yasuyuki Arai, Carlo Brugnara, Robertson D. Davenport, Richard M. Kaufman, Anne G. Hoen, Jenna Khan, C. Michael Knudson, Ryan A. Metcalf, Andres E. Mindiola Romero, Allison Mo, Richard Schäfer, Minoko Takanashi, Sajjad Afraz, Elizabeth S. Allen, Jennifer Andrews, Konstanze Aurich, John Casey, Claudia S. Cohn, Jensyn K. Cone Sullivan, Clara C. Cousins, Elizabeth P. Crowe, Valeria De Giorgi, Meghan Delaney, Regina M. DelBaugh, Colleen W. Gilstad, Alexander Gofton, Jeanne E. Hendrickson, Kate Hill, Keenan O. Hogan, Catherine Humbrecht, Kazuhiko Ikeda, Cyril Jacquot, Ayda Javanbakht, Justin E Juskewitch, Wen Lu, Monique M. Menzies Wojtowicz, Maureen J. Miller, Georgia Mills, Anna C. Nelson, Monica B. Pagano, Marie C. Pauly, Jessica L. Poisson, Jay S. Raval, Nabiha H. Saifee, Nikitha Samy, Tomohiko Sato, Yoshinori Takeda, Suzanne R. Thibodeaux, Pierre Tiberghien, Sheryl van Nunen, Mrigender S. Virk, Kamille West-Mitchell, Erica M. Wood, Jun Yamanouchi, Satoshi Yoshihara, X. Long Zheng, Alyssa Ziman, Nancy M. Dunbar
Institutions: Dartmouth–Hitchcock Medical Center, Dartmouth College, University of Virginia Health System, University of Iowa Health Care, University of Utah, University of Utah Health Care, University of New Mexico, Monash University, University of Freiburg, University Medical Center Freiburg, Japanese Red Cross Society, Japan, Stanford Medicine, Stanford University, University of California San Diego, Vanderbilt University Medical Center, Universitätsmedizin Greifswald, Australian Red Cross Lifeblood, University of Minnesota, University of Michigan, University of California, Los Angeles, Johns Hopkins University, National Institutes of Health, Children's National, Virginia Commonwealth University, MedStar Georgetown University Hospital, Commonwealth Scientific and Industrial Research Organisation, Emory Healthcare, Princess Alexandra Hospital, University of Kansas Medical Center, Établissement Français du Sang, Fukushima Medical University, The University of Texas Southwestern Medical Center, Mayo Clinic, Macquarie University, Gosford Hospital, University of Washington, Duke University, University of Vermont, Seattle Children's Hospital, The Jikei University Hospital, Université Marie et Louis Pasteur, Ehime University, Hyogo Medical University
Language: English
Subfield: Biochemistry
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W7204112843