A major new study published in JAMA Internal Medicine provides strong evidence that the allergy associated with certain tick bites and red meat may also put some patients at risk of sudden, dangerous allergic reactions during blood transfusions. Led by researchers at Dartmouth Health and the Geisel School of Medicine, the study provides compelling epidemiologic evidence for a condition researchers call Transfusion-Related Alpha-Gal Syndrome (TRAGS), which appears to affect certain type O patients receiving specific platelet or plasma products.
Alpha-gal syndrome (AGS) can develop after bites from certain ticks — most notably the Lone Star tick in the United States — trigger the immune system to produce antibodies against a sugar molecule called alpha-gal. Alpha-gal is found in most non-primate mammals but not humans. Once sensitized, people can experience delayed and potentially life-threatening allergic reactions — including hives, gastrointestinal symptoms, or anaphylaxis — after eating mammalian meat such as beef, pork, or lamb and, in some cases, consuming mammalian-derived products such as dairy or gelatin. The new findings suggest that alpha-gal sensitization may also have implications for certain blood transfusions.
Doctors at Dartmouth Hitchcock Medical Center (DHMC) first spotted the pattern after noticing an unusual increase in severe allergic reactions among patients with blood type O. Specifically, the reactions occurred when type O patients received platelets or plasma from donors with blood type B or AB. The B blood-group antigen is structurally similar to alpha-gal, leading researchers to hypothesize that pre-existing antibodies against alpha-gal may recognize B antigen in the transfused product and trigger an allergic reaction.
To determine how widespread the phenomenon might be, researchers analyzed 558,823 platelet and plasma transfusions across 40 hospitals in five countries, documenting 1,744 allergic transfusion reactions. They compared reactions according to donor and recipient blood groups and grouped participating sites according to whether they were located in regions with high or low prevalence of alpha-gal syndrome.
The results revealed a striking geographic pattern. Among type O recipients at US sites in regions where AGS is common, receiving B or AB platelets or plasma was associated with nearly four times the risk of an allergic transfusion reaction compared with receiving type O products. The association was even stronger when researchers examined moderate-to-severe reactions among type O patients receiving type B products. Importantly, the same pattern was not detected at sites outside the United States, strengthening the suspected connection to alpha-gal sensitization.
Dr Richard M Kaufman, one of the lead authors, explained the potential impact on transfusion practices: “We anticipate that this will change transfusion practices in the US, at least in AGS high-prevalence regions. 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.”
The findings take on added significance as ticks associated with AGS expand into new territories. Senior author Dr Nancy M Dunbar emphasized: “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. 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. Even if it’s an abundance of caution, it could save the patient’s life.”
Blood transfusions remain essential, life-saving treatments, and the findings should not discourage patients from receiving them when needed. Rather, the study suggests that transfusion services in regions where AGS is common should consider strategies to reduce the risk of giving B- or AB-group platelets or plasma to type O patients. The researchers caution that the study provides epidemiologic evidence for TRAGS rather than directly confirming alpha-gal allergy in every patient who experienced a reaction, and further research will be needed to better understand the mechanism and determine the most effective precautions.
