Background Allergic transfusion reactions (ATRs) represent a common adverse event, particularly with plasma rich blood components like platelets. While most are mild, severe (anaphylactic) reactions can occur, posing significant risks. The underlying pathophysiology is thought to involve complex interactions between donor factors and recipient susceptibility, often mediated by IgE but potentially involving other mechanisms like passive transfer of inflammatory mediators. Our study details two cases of anaphylactic reaction caused by platelet products from the same donor to explore potential underlying factors.

Methods

A retrospective investigation was initiated following the two reactions. To investigate potential mechanisms, we applied the Milliplex 48-plex human cytokine panel to compare levels of plasma cytokines in residual donor product, post-transfusion plasma from both affected recipients, and plasma from three random platelet units. All tests were performed in triplicate.

Results Both reactions were reported as anaphylactic and resolved with epinephrine. Neither recipient had a prior history of allergy or ATRs. Hemovigilance investigation showed that both reactions linked to apheresis platelet units originating from the same donor who is previously a long-time and frequent donor, had donated a separate product two months earlier that also resulted in an anaphylactic reaction. Consequently, the donor was indefinitely deferred from the donor pool.

Cytokine analysis demonstrated that several pro-inflammatory cytokines were elevated in the remaining donor product, including notable increases in TNFa, IL-9, and IL-13, along with chemokines including CCL22 and CCL11. These cytokines are implicated in mast cell function, eosinophil recruitment, Th2 immunity, and IgE class-switching, all potentially contributing to or amplifying an allergic/anaphylactic state. Recipient post-transfusion plasma contained elevated levels of CCL2, IL-10, and IL-6, all inflammatory mediators known to be pre-stored in basophil granules and suggestive of an anaphylactic response.

Conclusion These cases highlight the complex mechanisms of ATRs and suggest that anaphylactic transfusion reactions may be related to passively transfused biologically active mediators or other factors within the donor component, as evidenced by a single donor causing multiple anaphylactic reactions in different recipients across different donations. The findings underscore the importance of donor history review (identifying potentially problematic donors) and potential of personalized transfusion approaches to enhance patient safety and efficacy in transfusion medicine, setting the stage for further investigations for pathophysiology of ATRs.