B-Containing Transfusions Linked to Alpha-Gal Reactions

A large international retrospective cohort study found evidence that alpha-gal syndrome may contribute to allergic transfusion reactions when blood type O recipients receive plasma or platelets containing B antigen, particularly in US regions where alpha-gal syndrome is prevalent.

The analysis included 558,823 platelet and plasma transfusions performed at 40 sites in five countries. Allergic transfusion reactions occurred after 1,744 transfusions, or 0.3% of the total. Investigators compared reactions among recipients with type O blood who received group B or AB units with reactions among those who received group O units.

At nine US sites in high-prevalence alpha-gal regions, type O recipients had nearly four times the risk of an allergic reaction of any severity after B or AB products compared with O products (risk ratio [RR], 3.93; 95% CI, 2.96-5.21). In a subgroup analysis limited to group B units, the RR for moderate to severe reactions was 9.14 (95% CI, 5.39-15.52) in high-prevalence regions and 2.15 (95% CI, 1.34-3.47) in low-prevalence regions. However, the primary analysis found no overall excess of allergic reactions to combined B or AB units at the 15 low-prevalence sites. No signal consistent with transfusion-related alpha-gal syndrome was detected outside the United States.

Alpha-gal syndrome involves immunoglobulin E sensitization to galactose-alpha-1,3-galactose, a carbohydrate antigen. The findings suggest that transfusion-related alpha-gal syndrome may be a unique manifestation of the condition and a previously unrecognized transfusion risk.

The authors characterized the epidemiologic evidence as provocative. They said blood collectors and hospital transfusion services in high-prevalence regions should consider approaches to preventing severe allergic reactions involving group B or AB plasma or platelet units.

Source: Kaufman RM, Hoen AG, Khan J, et al. Epidemiologic study of transfusion-related alpha-gal syndrome. JAMA Intern Med. Published online August 24, 2026. doi:10.1001/jamainternmed.2026.3983.