Could alpha-gal reshape transfusion practice?

Clinical takeaway: Consider alpha-gal syndrome as a potential risk factor for allergic transfusion reactions in patients with type O blood, particularly in regions where AGS is common. The findings suggest that avoiding group B or AB platelet and plasma products in these patients may improve transfusion safety.

Alpha-gal syndrome (AGS), a tick-associated allergy caused by sensitization to the carbohydrate alpha-gal, has traditionally been linked to reactions after consuming mammalian meat products. Recent case reports raised concerns that the same immune response could trigger allergic reactions to transfused blood products containing blood group B antigens, leading investigators to examine whether transfusion-related alpha-gal syndrome (TRAGS) is a real and clinically meaningful entity.

In this retrospective cohort study, investigators analyzed 558,823 platelet and plasma transfusions performed at 40 centers across five countries between 2020 and 2024. Among U.S. hospitals in regions with high AGS prevalence, patients with type O blood who received group B or AB platelet or plasma products were nearly four times more likely to experience an allergic transfusion reaction than similar patients who received group O products. The signal was strongest with group B units, where the risk of moderate-to-severe reactions was more than ninefold higher. By contrast, no meaningful increase in overall risk was seen in U.S. regions with low AGS prevalence, and no excess risk signal emerged in Australia, France, Germany, or Japan.

The findings support the existence of TRAGS as a previously underrecognized transfusion complication and may influence how blood banks allocate platelet and plasma products, especially in parts of the U.S. where lone star tick exposure and AGS are common. Some institutions have already begun modifying transfusion practices to reduce exposure of type O recipients to B-antigen–containing products.

“We anticipate that this will change transfusion practices in the U.S., at least in AGS high-prevalence regions,” concluded lead author Richard M. Kaufman, MD.

Source: Kaufman RM, et al. (2026 Aug 24) JAMA Internal Medicine. Epidemiologic Study of Transfusion-Related Alpha-Gal Syndrome