Study in Which ARUP Played a Role Identifies New Transfusion Risk Linked to Alpha-Gal Syndrome

That a transfusion reaction that threatened the life of a 76-year-old patient during heart surgery originated with a tick bite may seem far-fetched, but the case prompted researchers to perform an international epidemiologic study to investigate a previously unrecognized risk of transfusion.

Richard Kaufman, MD, Principal Investigator; Professor of Pathology and Laboratory Medicine at the Geisel School of Medicine at Dartmouth College

Findings of the study in which ARUP Laboratories participated are detailed in an article published today in the journal JAMA Internal Medicine. This study provides important evidence supporting the existence of a new category of potentially lethal transfusion reactions, said Richard Kaufman, MD, principal investigator and a professor of Pathology and Laboratory Medicine at the Geisel School of Medicine at Dartmouth College in New Hampshire.

Kaufman said the case drew the interest of researchers at Dartmouth Hitchcock Medical Center because the patient, who had type O blood, was nearing the end of a successful surgery when he received a unit of type B platelets and his blood pressure plummeted suddenly, signaling a severe allergic reaction. Only rapid intervention by his care team saved his life.

A laboratory test later showed that the man had antibodies associated with alpha-gal syndrome (AGS), an allergic condition that can develop after a person is bitten by the lone star tick, a species prevalent in the Southeast and along the Atlantic Coast. AGS typically manifests as an allergic reaction to red meat or other mammalian products.

To explore further whether AGS played a role in the transfusion reaction, Kaufman and the paper's senior author, Nancy Dunbar, MD, also a professor of Pathology and Laboratory Medicine at Dartmouth, engaged colleagues at 40 academic medical centers in five countries in an epidemiologic study. The researchers included Ryan Metcalf, MD, CQA(ASQ), section chief of Transfusion Medicine at ARUP and University of Utah Health, who is a coauthor of the study along with Kaufman, Dunbar, and others.

Ryan Metcalf, MD, CQA(ASQ), Section Chief of Transfusion Medicine at ARUP and University of Utah Health

Their research analyzed data on 558,823 platelet or plasma transfusions and allergic transfusion reactions (ATRs) from 2020 to 2024. Researchers compared patients with type O blood who received B or AB units with patients with type O blood who received O units in areas where AGS is prevalent and where the allergic condition is not.

"The results were striking," Kaufman said. Among patients with type O blood in high-prevalence AGS regions, those who received type B or AB plasma or platelet products were nearly four times more likely to experience ATRs than those receiving type O products. The risk of moderate to severe reactions was even greater for the affected group. Patients receiving type B products were more than nine times as likely to experience a moderate or severe allergic reaction compared with the reference group, he said.

In contrast, no comparable increase in risk was detected at sites where AGS is virtually nonexistent, such as U of U Health, according to Metcalf.

Kaufman explained that galactose-α-1,3-galactose, the sugar molecule that triggers AGS, is structurally almost identical to the B blood group antigen found in type B and AB blood products.

In people with AGS, antibodies that were created after a tick bite may recognize and bind to these transfused B antigens, triggering an allergic reaction. Patients with type O blood appear to be at greatest risk because they do not naturally carry B antigens. As a result, some blood type O patients with AGS-related antibodies may experience ATRs, ranging from hives and itching to life-threatening anaphylaxis, when they receive plasma or platelets from type B or AB donors.

Kaufman noted that several reported ATR cases that were part of the study, including the case involving the 76-year-old patient who underwent heart surgery, involved patients with no history of meat allergy, suggesting that alpha-gal sensitization may go undetected in many individuals who may not know they face a risk of transfusion reaction.

"Certainly, people in transfusion medicine need to know about this risk, but really, so do all physicians who are caring for patients who may need transfusions, whether they be surgeons, anesthesiologists, hematologists, and so on," he said.

Kaufman, Dunbar, Metcalf, and the study's other authors said further research is needed to confirm the findings prospectively, better understand the underlying mechanisms, and identify practical approaches to reducing risk.

However, their findings are already influencing clinical practice. Because Dartmouth Hitchcock is in an area where AGS is prevalent, it has stopped providing B- or AB-containing platelet products to patients with type O blood, Kaufman said, adding that blood donor centers and transfusion services may need to rethink inventory management, including redistributing certain blood products to areas where AGS is rare.

At U of U Health, broad screening of patients for AGS is unlikely because AGS prevalence is so low in the West, Metcalf said. Instead, he and his colleagues are exploring ways to identify and flag any patients who are known to have tested positive for AGS so that transfusion strategies can be adjusted if they need blood products in the future.

For Metcalf, the study is important not only for the significance of its findings, but also because it reflects a broader mission to help clinicians and patients better understand both the benefits and risks of transfusion. Blood transfusions save lives every day, he said, but informed medical decisions require accurate information about potential complications as well.

"My interest has been understanding what are the actual risks and what are the actual benefits," Metcalf said. "So, if a patient or clinician is making that decision, they know what the real risks are."

Research that quantifies both sides of that equation ultimately helps patients and their caregivers make the best medical decisions possible.

Lisa Carricaburu, [email protected]