Patients with blood type O who received B or AB plasma or platelets had a higher risk of allergic transfusion reactions than those who received O products at US sites in regions with high alpha-gal syndrome prevalence.

Investigators conducted an international, multicenter, retrospective cohort study of platelet and plasma transfusions administered from 2020 through 2024 at academic medical centers in the US, Australia, Japan, Germany, and France. Sites were classified as having high or low alpha-gal syndrome (AGS) prevalence based on known geographic distributions. Overall, 558,823 platelet and plasma transfusions at 40 sites in 5 countries; allergic transfusion reactions (ATRs) occurred in 1,744 transfusions (0.3%).

Investigators compared ATR rates among patients with blood type O who received B or AB plasma or platelets with rates among patients with blood type O who received O products at the same sites. The primary measure was the overall risk ratio of ATRs to B or AB products in AGS high-prevalence vs low-prevalence clusters. They also examined reaction severity, the ABO group of transfused products, and reactions among patients with blood type B.

At 9 US sites in the AGS high-prevalence cluster, patients with blood type O who received B or AB products had 3.93 times the risk of an ATR of any severity compared with patients who received O products. In contrast, the primary analysis at 15 US sites in the AGS low-prevalence cluster did not detect excess ATRs to B or AB products. Compared with the low-prevalence cluster, the high-prevalence cluster had 5 additional ATRs of any severity and 11 additional moderate to severe ATRs per 10,000 transfusions.

Risk also differed by the ABO group of the transfused product. In the AGS high-prevalence cluster, B products were associated with 4.48 times the risk of an ATR compared with O products, whereas AB products were associated with 2.53 times the risk. A products were not associated with excess ATR risk. In the AGS low-prevalence cluster, the authors found no statistically significant overall differences in ATR rates among patients with blood type O receiving B, AB, or A products compared with O products.

The association was stronger for moderate to severe reactions. Among patients with blood type O who received B products, the risk of moderate to severe ATRs was 9.14 times that of the reference group in the AGS high-prevalence cluster and 2.15 times that of the reference group in the low-prevalence cluster. The excess risk was statistically significantly greater in the high-prevalence cluster.

Additional findings supported the geographic and blood type pattern. At AGS high-prevalence sites, excess ATRs were not observed among patients with blood type B who received B or AB products. Patients with blood types B or AB are relatively protected from producing immunoglobulin E to alpha-gal and developing AGS. Investigators also did not detect a signal consistent with transfusion-related alpha-gal syndrome (TRAGS) outside the US or at the single AGS high-prevalence pediatric hospital.

Because of its retrospective design, the authors could not test recipients for alpha-gal immunoglobulin E or determine whether they had a history of AGS, preventing direct confirmation that AGS accounted for the observed reactions. ATRs were uncommon and generally depended on passive clinician reporting, raising the possibility of underreporting. Investigators also could not exclude greater investigation or reporting of reactions to B or AB products at sites where AGS was more prevalent. Geographic misclassification and factors unrelated to AGS could also have contributed to the findings.

The findings provided epidemiologic evidence consistent with TRAGS as a potentially previously unrecognized transfusion risk, although prospective validation is needed. Investigators suggested that hospitals in regions with high AGS prevalence evaluate local reaction patterns and consider approaches to reducing risk from B antigen-containing products.

“This cohort study provides provocative epidemiologic evidence consistent with TRAGS representing a newly recognized risk to recipients of blood transfusions,” wrote lead study author Richard M. Kaufman, MD, of Dartmouth Hitchcock Medical Center, and colleagues.

Disclosures: Several researchers reported financial relationships with industry. No study funding was reported.

Source: JAMA Internal Medicine