Tranexamic acid (TXA) is an
antifibrinolytic agent that blocks
plasmin formation. Because
plasmin is known to promote inflammatory and immunosuppressive responses, we explored the possibility that
plasmin-mediated immunosuppression in patients undergoing cardiac surgery can be directly reversed by TXA and decrease postoperative
infection rates. The modulatory effect of TXA on inflammatory
cytokine levels and on innate immune cell activation were evaluated with multiplex
enzyme-linked
immunosorbent assay and flow cytometry, respectively. Postoperative
infection rates were determined in patients undergoing cardiac surgery and randomized to TXA (ACTRN12605000557639; http://www.anzca.edu.au). We demonstrate that TXA-mediated
plasmin blockade modulates the immune system and reduces surgery-induced immunosuppression in patients following cardiac surgery. TXA enhanced the expression of immune-activating markers while reducing the expression of immunosuppressive markers on multiple myeloid and lymphoid cell populations in peripheral blood. TXA administration significantly reduced postoperative
infection rates, despite the fact that patients were being administered prophylactic
antibiotics. This effect was independent of the effect of TXA at reducing blood loss. TXA was also shown to exert an immune-modulatory effect in healthy volunteers, further supporting the
fibrin-independent effect of TXA on immune function and indicating that baseline
plasmin levels contribute to the regulation of the immune system in the absence of any comorbidity or surgical
trauma. Finally, the capacity of TXA to reduce
infection rates, modulate the innate immune cell profile, and generate an
antifibrinolytic effect overall was markedly reduced in patients with diabetes, demonstrating for the first time that the diabetic condition renders patients partially refractory to TXA.