Tranexamic acid for haemostasis and beyond: does dose matter?

Abstract

Tranexamic acid (TXA) is a widely used antifibrinolytic agent that has been used since the 1960’s to reduce blood loss in various conditions. TXA is a lysine analogue that competes for the lysine binding sites in plasminogen and tissue-type plasminogen activator impairing its interaction with the exposed lysine residues on the fibrin surface. The presence of TXA therefore, impairs the plasminogen and tPA engagement and subsequent plasmin generation on the fibrin surface, protecting fibrin clot from proteolytic degradation. However, critical lysine binding sites for plasmin(ogen) also exist on other proteins and on various cell-surface receptors allowing plasmin to exert potent effects on other targets that are unrelated to classical fibrinolysis, notably in relation to immunity and inflammation. Indeed, TXA was reported to significantly reduce post-surgical infection rates in patients after cardiac surgery unrelated to its haemostatic effects. This has provided an impetus to consider TXA in other indications beyond inhibition of fibrinolysis. While there is extensive literature on the optimal dosage of TXA to reduce bleeding rates and transfusion needs, it remains to be determined if these dosages also apply to blocking the non-canonical effects of plasmin.

A systematic review and meta-analysis of systematic and topical tranexamic acid administration in aesthetic plastic surgery

“…However, in our systematic review and meta-analysis, significant heterogeneity was observed in the blood loss volume analysis, mainly due to differences in surgery type, blood loss volume calculation method (Gerdessen et al 2021 ; Sokoliuk and Levchenko 2022 ), and TXA dose (Taam et al 2020 ; Lam et al 2023 ). There may be significant differences in blood loss volume between different surgeries, such as breast aesthetic surgery, liposuction, or rhinoplasty.…”

Plasminogen degrades α-synuclein, Tau and TDP-43 and decreases dopaminergic neurodegeneration in mouse models of Parkinson’s disease

“…Furthermore, it is widely accepted that plasmin/plasminogen exerts cell-associated activities by binding to the cell surface via surface plasminogen receptors. The binding of plasminogen with these cell receptors triggers downstream intracellular signaling pathways associated with immune cell recruitment, inflammation modulation and improved wound healing 29 . To date, at least twelve plasminogen receptors have been identified, and their functions have been extensively studied 29 .…”

“…The binding of plasminogen with these cell receptors triggers downstream intracellular signaling pathways associated with immune cell recruitment, inflammation modulation and improved wound healing 29 . To date, at least twelve plasminogen receptors have been identified, and their functions have been extensively studied 29 . However, by using confocal microscopy, ELISA and plasmin activity analysis, we demonstrated that plasminogen itself rapidly entered the cytoplasm and that most plasminogen eventually accumulated in the nucleus.…”

The Roles of Fibrinolytic Factors in Bone Destruction Caused by Inflammation

“…The alteration in plasmin activity may impact the progression of chronic inflammatory diseases. Additionally, tranexamic acid, a lysine analogue that competes for lysine-binding sites in Plg, has been shown to exhibit anti-inflammatory effects by inhibiting plasmin in patients undergoing cardiac surgery [ 74 ]. TXA also suppresses the expression of inflammatory cytokines and inhibits inflammatory osteoclastogenesis.…”