The impacts of tranexamic acid on immune system during trauma

Abstract

Tranexamic acid (TXA) is a synthetic, reversible competitive inhibitor of the lysine receptor on plasminogen. It inhibits plasmin, the active form of plasminogen, from binding to and degrading the fibrin matrix. The mechanism not only effectively mitigates bleeding complications in various hemostatic challenges but also lowers mortality, with minimal adverse effects, including postoperative seizures in specific situations. Although the effectiveness of TXA in acute trauma is well-established, its impact on both the innate and adaptive immune systems underscore the need to address existing knowledge gaps. This review aims to shed light on both the pro- and anti-inflammatory effects of TXA in the context of traumatic injuries. Moreover, we will argue about TXA immunological effects through its anti-plasmin activity, stemming from its high affinity for lysine residues on plasmin and fibrin residues on plasminogen, leading to reduced vascular permeability, decreased allergic responses, and diminished inflammation. Furthermore, it will be disclosed that TXA administration significantly inhibited neutrophil extracellular trap (NETosis) formation during trauma injuries. More importantly, we will provide profound insights about the prominent factors orchestrating TXA immunomodulatory and prophylactic effects during trauma, including the type of trauma, presence of infection, TXA dosage, duration since trauma onset, the persistence of TXA treatment and genetic background.