Lebanon, New Hampshire—A large international study led by researchers at Dartmouth Health and the Geisel School of Medicine at Dartmouth has identified a previously overlooked transfusion risk associated with alpha-gal syndrome, a tick-borne allergy that can cause severe reactions to mammalian meat and animal-derived products. The findings suggest that some patients with the condition, particularly those with type O blood, may face an elevated risk of allergic reactions when they receive plasma or platelet products from donors with type B or AB blood. The researchers describe this phenomenon as transfusion-related alpha-gal syndrome, or TRAGS, and say it could influence transfusion practices in regions where alpha-gal syndrome is common.
Alpha-gal syndrome is caused by an immune response to galactose-alpha-1,3-galactose, commonly known as alpha-gal. This sugar is found in most nonprimate mammals but is absent from humans and other Old World primates. In susceptible people, a bite from a Lone Star tick can stimulate the production of immunoglobulin E, or IgE, antibodies directed against alpha-gal. Once sensitization has occurred, exposure to the molecule through beef, pork, lamb, dairy products, gelatin, or other mammalian-derived materials may activate mast cells and basophils. The resulting release of histamine and other inflammatory mediators can produce hives, abdominal pain, vomiting, swelling, breathing difficulty, cardiovascular instability, and, in severe cases, anaphylaxis.
Unlike many food allergies, alpha-gal reactions are often delayed. Symptoms may emerge several hours after exposure, a pattern believed to be related to the digestion and absorption of lipid-associated alpha-gal molecules in the intestine. That delay can make the source of a reaction difficult to identify, especially in patients who have undergone surgery or received multiple medications and blood products. The condition has also become more prominent as Lone Star ticks expand their geographic range and as clinicians improve recognition and testing. The new study indicates that the clinical relevance of alpha-gal antibodies may extend beyond food and pharmaceutical exposures to components of transfused blood products.
The investigation was prompted by observations at Dartmouth Hitchcock Medical Center, where clinicians reported an increase in serious allergic reactions among type O patients who received platelets or plasma from type B or AB donors. Allergic transfusion reactions are not unusual, but they are generally associated with antibodies or proteins in the donor’s plasma. Symptoms can include flushing, itching, hives, wheezing, low blood pressure, and, rarely, life-threatening anaphylaxis. The Dartmouth team suspected that some of the unexplained reactions might involve pre-existing IgE antibodies against alpha-gal in recipients who had previously been bitten by ticks.
To examine that possibility, researchers analyzed more than 550,000 platelet and plasma transfusions recorded at 40 medical centers in five countries. The study included nine United States sites located in areas with high concentrations of patients diagnosed with alpha-gal syndrome. Investigators compared reported allergic reactions according to the recipient’s ABO blood group and the blood group of the donor product. Among type O patients at the high-prevalence US centers, reactions occurred significantly more often after transfusion of B or AB products than after transfusion of O products. The pattern was not presented as proof that every reaction was caused by alpha-gal, but it was consistent with the team’s hypothesis that alpha-gal sensitization can contribute to transfusion-associated illness.
The biological explanation is complex because plasma and platelet products contain more than cells alone. Platelet units are suspended in plasma, and plasma contains antibodies, proteins, lipids, and other soluble molecules. Some biological materials used during collection, processing, or storage may also contain animal-derived components. In people with alpha-gal-specific IgE, even a small amount of the target sugar could theoretically cross-link antibodies bound to mast cells and basophils, initiating degranulation. The ABO system may modify this risk through differences in blood-group antigens, naturally occurring antibodies, and the molecular composition of plasma products. The researchers emphasize that the precise source and form of alpha-gal involved in these reactions still require laboratory confirmation.
Type O recipients may be particularly vulnerable because transfusion services sometimes use platelet or plasma products that are not identical in ABO type when supplies are limited or when urgent treatment is required. Although red blood cell compatibility remains central to transfusion safety, platelets and plasma involve additional considerations. Platelets express ABO antigens variably, while plasma contains donor antibodies that can react with antigens on recipient cells. In routine practice, hospitals balance compatibility, availability, urgency, and product shelf life. The new findings suggest that alpha-gal status may eventually become another factor in that calculation, especially in regions where tick exposure and alpha-gal sensitization are widespread.
Richard M. Kaufman, the study’s corresponding author and a professor of pathology and laboratory medicine at Geisel, said the results could change transfusion procedures in high-prevalence areas. Dartmouth Hitchcock Medical Center has already stopped giving B or AB platelet products to type O patients when suitable alternatives are available, a precaution intended to reduce the possibility of a severe reaction. Nancy M. Dunbar, the study’s senior author and a professor of medicine and pathology and laboratory medicine, said the expanding distribution of ticks is bringing clinicians into contact with diseases and immune complications that were previously uncommon in their practices.
The researchers caution that the findings do not mean type O patients should avoid necessary transfusions or that all people with alpha-gal syndrome will react to B or AB plasma or platelets. Blood transfusion remains a lifesaving treatment, and withholding a needed product can itself be dangerous. Instead, the study supports improved recognition of alpha-gal syndrome in transfusion histories, closer investigation of severe or unexplained allergic reactions, and further research into how alpha-gal enters blood products and interacts with recipient antibodies. Future studies will need to confirm the mechanism with laboratory assays, determine the absolute risk for sensitized patients, and establish whether special processing or donor-selection strategies can prevent TRAGS without restricting access to urgently needed blood components.
The study, “Epidemiologic Study of Transfusion-Related Alpha-Gal Syndrome,” was published in JAMA Internal Medicine on August 24, 2026. Its authors include investigators from Dartmouth Health, Geisel School of Medicine at Dartmouth, and collaborating institutions in the United States and abroad. The work carries several reported financial and professional disclosures involving blood-product manufacturers, pharmaceutical companies, professional organizations, and medical-data projects. Even so, the authors argue that the consistency of the ABO-linked reaction pattern across multiple high-prevalence sites warrants attention from hospitals and transfusion services. As alpha-gal syndrome becomes more common, transfusion medicine may need to account for an allergy that begins not with a meal, but with a tick bite and an otherwise routine medical procedure.
Subject of Research: People
Article Title: Epidemiologic Study of Transfusion-Related Alpha-Gal Syndrome
News Publication Date: 24-Aug-2026
Web References: https://jamanetwork-com.dartmouth.idm.oclc.org/journals/jamainternalmedicine/fullarticle/2852649
References: https://doi.org/10.1001/jamainternmed.2026.3983
Keywords: alpha-gal syndrome, transfusion-related alpha-gal syndrome, TRAGS, tick-borne disease, Lone Star tick, platelet transfusion, plasma transfusion, blood type O, allergic transfusion reaction, anaphylaxis, transfusion medicine, Dartmouth Health
