Tick-borne meat allergy linked to allergic reactions when type O patients get type B plasma or platelets

Doctors at a hospital in New Hampshire kept seeing the same odd thing. A patient with type O blood would be given platelets or plasma from a type B donor, a routine substitution, and have a severe allergic reaction. They suspected a culprit that had nothing obvious to do with blood: a meat allergy spread by ticks.

A study published in JAMA Internal Medicine in August put the hunch to a test across 40 hospitals in five countries. The pattern the doctors predicted is the pattern they found. The excess of reactions appeared in the parts of the United States where the tick-borne allergy is common, with no overall excess elsewhere. The risk to any one patient is low, and the study could not confirm the allergy in a single person who reacted. But at least one hospital has already changed what it gives.

What alpha-gal syndrome is

The allergy has an unwieldy name. In the words of the US Centers for Disease Control and Prevention, alpha-gal syndrome (AGS) is an emerging, tick bite-associated allergic condition characterized by a potentially life-threatening immunoglobulin E (IgE)-mediated hypersensitivity to a sugar called alpha-gal. Immunoglobulin E is the type of antibody behind allergies. Hypersensitivity means an overreaction of the immune system.

Alpha-gal is made by most mammals and not by people. The sugar is present in the saliva of the lone star tick, and after a bite some people’s immune systems respond by making antibodies against it. The initial IgE sensitization follows a bite from the Amblyomma americanum (lone star) tick in the United States, a review explains. After that, eating meat from a mammal can set off a reaction.

The reactions are unusual for a food allergy in that they are slow. A pooled analysis of 15 studies comprising 1162 AGS patients found that hives were the most common single symptom, in about 64%, and that seven in ten had at least one stomach or bowel symptom. In more than nine in ten, symptoms began an hour or more after the meal. Nearly four in five remembered a tick bite.

That delay makes the condition hard to spot. The same review notes that the nonspecificity of the symptoms can delay the diagnosis of AGS for years.

It is not rare where the tick lives. A federal analysis of laboratory records found that over six years, 90,018 (30.5%) persons received a positive test result out of roughly 295,000 tested. The suspected cases predominantly occurred in counties within the southern, midwestern, and mid-Atlantic regions of the country. The same report states that no treatment or cure is currently available. Management rests on avoiding the triggers.

Why a meat allergy could matter in a transfusion

The connection is a coincidence of chemistry. Blood groups are defined by sugar markers, called antigens, on the surface of cells. The marker for group B looks very much like alpha-gal. A report on the study from AABB, a professional body for transfusion medicine, puts it this way: its structure closely resembles the human blood group B antigen, and many alpha-gal IgE antibodies cross-react with B antigen. To cross-react is to mistake one target for another.

People with blood group B or AB carry that marker themselves, so their immune systems treat anything resembling it as their own. People with group O or A do not.

Red blood cells are matched strictly to the patient’s blood group. Platelets, the cell fragments that help blood clot, and plasma, the liquid part of blood, are handled more loosely because supplies are short and platelets expire in days. In the report’s words, transfusion services routinely give group B or AB plasma and platelets to type O patients to avoid product outdating or in bleeding emergencies.

Put those facts together and a prediction follows. A type O patient who has been sensitized to alpha-gal by a tick, and who is then given a group B unit, receives a dose of something their allergy antibodies recognize.

The paper notes that individual cases had already pointed that way. Recent case reports suggest that B antigen-containing blood products may be associated with anaphylactic transfusion reactions in such patients. Anaphylactic means a severe, whole-body allergic reaction.

How the transfusion study tested the idea

The researchers, led by Richard Kaufman and Nancy Dunbar of Dartmouth Hitchcock Medical Center, turned the hunch into a test that could fail.

They wrote down their prediction first. Before data collection, the hypothesis was that if transfusion-related alpha-gal syndrome (TRAGS) is a true clinical entity, excess ATRs to group B or AB units would be detected in AGS high-prevalence regions exclusively. An ATR is an allergic transfusion reaction, and prevalence means how common a condition is. If the extra reactions showed up everywhere, or nowhere, the idea would be in trouble.

The study was retrospective, meaning it used records already kept. It was an international, multicenter, retrospective cohort study at academic medical centers, covering transfusions given from 2020 to 2024. American hospitals were sorted into two groups according to how common the allergy is in their area.

Within each hospital the comparison was simple: patients with blood type O who received B or AB units and patients with blood type O who received O units. The second group is the yardstick. As the AABB report explains, the design meant every site served as its own control, so differences between hospitals in how carefully reactions are recorded could not produce the result.

In all, platelet and plasma transfusions at 40 sites in 5 countries were analyzed. There were 558,823 of them.

Where the excess allergic reactions appeared

Allergic reactions were uncommon. They followed 1,744 of the transfusions, or 0.3%.

Hospitals	Type O patients given B or AB units, compared with type O patients given O units
US, allergy common (9 sites)	3.93 times the rate of allergic reactions
US, allergy uncommon (15 sites)	No excess in the main analysis
Outside the US	No signal

In the nine American hospitals where the allergy is common, type O patients given B or AB units had reactions at 3.93 times the rate of type O patients given O units, with a plausible range of 2.96 to 5.21.

In the 15 American hospitals where it is uncommon, the main analysis showed nothing: excess ATRs to B or AB units were not detected.

The signal sharpened when the researchers narrowed the question to group B units and to the more serious reactions. In the high-prevalence hospitals, moderate to severe reactions were about nine times as frequent in type O patients given B units. In the low-prevalence hospitals the figure was about twice, a smaller excess that the main analysis had not picked up.

Two further checks fit the explanation. According to the AABB report, group A units were not associated with excess risk, as would be expected if the B marker is what matters. And patients who were themselves group B showed no excess when given B units.

Abroad there was nothing. Outside the US, a signal consistent with TRAGS was not detected. The AABB report names the countries: no excess reactions were detected in Australia, France, Germany or Japan.

The authors chose a careful word for what they had. This cohort study provides provocative epidemiologic evidence that TRAGS may be a unique manifestation of AGS and a previously unrecognized risk associated with transfusion. Epidemiologic evidence is evidence from patterns across populations.

What hospitals are doing about transfusion reactions

The hospital where the question started has already acted. “We anticipate that this will change transfusion practices in the U.S., at least in AGS high-prevalence regions,” Kaufman said in a statement from Dartmouth Health. The release says the hospital has stopped giving B or AB platelets to type O patients.

Dunbar tied the problem to a changing map of tick-borne disease. “The changing climate and ensuing greater proliferation of ticks is leading to illnesses and symptoms we had not seen before, and we continue to learn about them in real time,” Dunbar said.

The paper’s own recommendation is addressed to institutions. In AGS high-prevalence regions, blood collectors and hospital transfusion services should consider approaches to preventing severe ATRs from B or AB plasma or platelet units.

The AABB report lists what those approaches might be. They include testing for the allergy antibody when a reaction is investigated, and using group A rather than AB plasma in bleeding emergencies. A further idea is logistical: blood collectors could consider redistributing B and AB units toward lower-prevalence regions.

What the study cannot show about alpha-gal and transfusion

Whether the patients who reacted had the allergy. This is the main gap, and the authors acknowledge it. As the AABB report summarizes, the retrospective design meant patient sera could not be tested to confirm alpha-gal IgE, and no patient AGS history was available, so the link to sensitization remains inferential. Sera are blood samples. The study shows that reactions track the geography of the allergy. It does not show the allergy in the people who reacted.

How large the risk is for one patient. The results are ratios. With allergic reactions following 3 in every 1,000 transfusions, even a fourfold increase leaves the chance for an individual patient small.

How many reactions go unrecorded. Hospitals rely on staff to report reactions. The report cautions that passive reporting likely undercounts reactions.

Whether awareness skewed the count. Doctors at hospitals in tick country, having heard of the idea, may have looked harder. In the report’s words, rising awareness of TRAGS during the study period may also have prompted clinicians at high-prevalence sites to investigate suspected reactions more actively. The own-control design guards against some of this but not all.

Why nothing appeared abroad. The allergy exists in other countries, carried by other ticks. The absence of a signal there may reflect how rarely those hospitals give B units to O patients, or how reactions are recorded.

Red blood cells. The study examined platelets and plasma, the products that are commonly given across blood groups.

Which blood product a patient receives depends on their blood group, what is available and the urgency, which is assessed by their doctor.

Across 558,823 platelet and plasma transfusions, type O patients given group B or AB units had nearly four times the usual rate of allergic reactions at US hospitals in areas where tick-borne alpha-gal syndrome is common and no overall excess elsewhere, in a records-based study that could not test any patient for the allergy and in which allergic reactions of any severity followed 0.3% of transfusions.