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Transfusion‐related alpha‐gal syndrome: Two new cases expanding the demographic and geographic spectrum, and evidence of a diagnostic gap in allergic transfusion reaction evaluation

Year: 2026
Type: article
Study design: Observational Study
Abstract: BACKGROUND: Transfusion-related alpha-gal syndrome (TRAGS) has recently been proposed as a cause of allergic transfusion reactions (ATRs) in which alpha-gal-specific IgE in sensitized group O (or potentially group A) recipients reacts with epitopes on group B or AB plasma-containing components. Fewer than 10 cases have been reported, all from the Northeast and mid-Atlantic United States, and alpha-gal-specific ATR evaluation practices are unstudied. STUDY DESIGN AND METHODS: Two patients with ATRs consistent with TRAGS at a large academic medical center in Nashville, Tennessee are reported alongside a 5-year retrospective cohort analysis of group O and A recipients experiencing ATRs following transfusion of group B or AB plasma-containing products. Alpha-gal IgE testing, AGS diagnosis documentation, and documented consideration of IgA deficiency were assessed for each qualifying reaction. RESULTS: Both index patients had pre-existing AGS diagnoses unrecognized at component selection; one was a 42-year-old female and the second an 83-year-old male. Among 50 qualifying ATRs in 44 patients, including 13 severe or anaphylactic reactions, alpha-gal IgE testing was not performed for any event, and no patient had a documented AGS diagnosis. IgA deficiency was considered in eight patients (18%), yielding no diagnoses. CONCLUSION: TRAGS occurs in the tick-endemic southeastern United States across a broader demographic range than previously recognized. IgA deficiency, present in <0.3% of the population, was considered in 18% of qualifying patients while alpha-gal sensitization, affecting 20%-30% in this region, was investigated in none. Integration of AGS history into pre-transfusion risk assessment and ATR evaluation protocols is warranted.
Source: Transfusion
Language: English
Subfield: Biochemistry
Field: Medicine
Open Access status: hybrid
Estimated APC paid: $4,100
OpenAlex ID: W7142505236
FWCI: 6.827
Cites: 31
Cited by: 2
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