Alpha-gal syndrome (AGS), the tickborne disease that triggers an allergic reaction to red meat and animal byproducts, may present an additional complication for patients who need blood transfusions, according to a study published this week in JAMA Internal Medicine. Patients with alpha-gal and type O blood may have severe allergic reactions after receiving a blood transfusion from a donor with type B or AB blood. 

Historically, clinicians haven’t considered donor and recipient blood types important when assessing the risk of allergic transfusion reactions. But researchers now think some people with alpha-gal syndrome may react to transfused blood products containing the type B antigen. The alpha-gal molecule closely resembles the B antigen, which may allow alpha-gal antibodies to mistakenly bind to it. 

To test their hypothesis, a team led by researchers from Dartmouth Hitchcock Medical Center (DHMC) analyzed data from nearly 559,000 platelet and plasma transfusions at 40 sites in five countries. 

Their findings showed that, in US regions with a high prevalence of alpha-gal syndrome (nine sites), there were significantly more allergic transfusion reactions among patients with O blood type who received B or AB units than among those with O blood type who received O units (risk ratio, 3.93). Excess allergic reactions were not seen when patients with blood type B were transfused with B or AB units.

We anticipate that this will change transfusion practices in the U.S., at least in AGS high-prevalence regions.

In areas with a low prevalence of alpha-gal syndrome (15 sites), the researchers did not identify increased allergic transfusion reactions among patients with O blood type who received B or AB units. At sites outside the United States, the team did not find a signal consistent with transfusion-related alpha-gal syndrome (TRAGS).

“We anticipate that this will change transfusion practices in the U.S., at least in AGS high-prevalence regions,” lead author and Dartmouth Professor of Pathology and Laboratory Medicine Richard M. Kaufman, MD, said in a Dartmouth Health news release. “DHMC has already taken the step to cease giving transfusions of B or AB platelets to O patients to avoid potential injury to these patients.”

In an accompanying commentary, Marie A. Hollenhorst, MD, PhD; Jacob R. Anderson, MD, PhD; and Walter Dzik, MD, all of Harvard Medical School, note that “this study provides the strongest data to date supporting the existence of TRAGS,” citing the large numbers of  both transfusions analyzed and participating sites across a wide geographic area.

While the number of allergic transfusion reactions attributed to alpha-gal syndrome is currently “vanishingly small,” continue the commentators, “physicians should be aware of TRAGS as a potential newly identified allergic transfusion reaction” and consider testing for anti–alpha-gal immunoglobulin E antibodies when evaluating blood transfusion candidates. 

“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,” said coauthor and DHMC pathologist Nancy M. Dunbar, MD. 

“AGS is a particularly fascinating and challenging tickborne disease as it causes this life-threatening allergy the patient did not have before, and now we know the risk is even greater for AGS patients who are type O. It is our hope that other hospitals, especially in regions with high tick populations, will follow DHMC’s lead and avoid B and AB units for O-group patients in need of platelet or plasma transfusion.”