Transfusion-related alpha-gal syndrome (TRAGS)
A newly identified potential risk for patients with alpha-gal syndrome (AGS)
TRAGS
It has been hypothesized that AGS may result in allergic transfusion reactions (ATRs) due to the structural similarity between the alpha-gal antigen and the Group B antigen. Dunbar et al have proposed a new entity which they term “transfusion-related alpha-gal syndrome (TRAGS).” They propose that patients with AGS may be at risk for severe and even fatal ATRs following exposure to Group B antigen and/or substance through plasma or platelet transfusions.
Background
Three published case series describe six Group O patients who experienced severe ATRs after receiving Group B plasma transfusions or a Group B platelet transfusion. In these reports, four of five patients had IgE alpha-gal antibodies. The remaining patient was not tested. One reaction resulted in a fatality.
All case reports published to date involve Group B transfusions to Group O recipients.
Further studies are needed to establish whether transfusion-related alpha-gal syndrome (“TRAGS”) is a true clinical entity.
Key publications
Key publications on transfusion-related alpha-gal syndrome
- Malard L, Beuscart C, de Chaisemartin L, et al. Association between group B major ABO-incompatible platelet or plasma transfusion and severe allergic reactions: A nationwide haemovigilance analysis suggesting a role for α-gal syndrome. A Biomedical Excellence for Safer Transfusion Collaborative study. Vox Sang. 2025;(vox.70136). doi:10.1111/vox.70136
- Jones VM, Nakahara H, Choudhary SK, et al. Immunologic investigation of an allergic transfusion reaction suspected due to alpha-gal syndrome. Transfusion. Published online September 12, 2025. doi:10.1111/trf.18405
- Dunbar NM, Kaufman RM, Bary KS, et al. ABO-mismatched platelet and plasma transfusion practices and the potential for transfusion-related alpha-gal syndrome: The Biomedical Excellence for Safer Transfusion Collaborative Study. Transfusion. 2025;(trf.18338). doi:10.1111/trf.18338
- Miller MJ, Lee P, Lee BG, Flegel WA, West-Mitchell K, Conry, Cantilena K, et al. Consideration for alpha-gal syndrome in two critically ill persons with group O blood who received group B plasma. Transfusion. 2024;64:949–51.
- Gilstad CW, Conry-Cantilena K, Zarpak R, Eder AF. An outbreak of anaphylactic transfusion reactions to group B plasma and platelets and its possible relationship to alpha-gal syndrome. Transfusion. 2023;63:1997–2000.
Highlights from
ABO-mismatched platelet and plasma transfusion practices and the potential for transfusion-related alpha-gal syndrome: The Biomedical Excellence for Safer Transfusion Collaborative Study
JDunbar NM, Kaufman RM, Bary KS, Bellairs GR, Cohn CS, Delettre F, Ditcham S, Duarte GC, Ellison A, Fachini R, George CE.
July, 2025
The following are excerpts were taken directly from this paper:
Key points
- “The existence and true incidence of TRAGS remains unknown at this time.”
- “Transfusion services should be aware of AGS and consider the possibility of TRAGS whenever a Group O patient experiences a severe ATR in the context of a Group B or AB plasma and/or platelet transfusion. In such cases, we suggest that patients be tested for IgE antibodies to alpha-gal with referral to allergy/immunology for patients who test positive.”
- “Such antibody-positive patients should also be restricted from receiving Groups B and AB plasma and platelets for future transfusions.”
- “Further basic science and epidemiological studies will be needed to determine whether and to what extent AGS is related to the risk of severe ATRs.”