Tranexamic acid: Beyond antifibrinolysis

Abstract

Tranexamic acid (TXA) is a popular antifibrinolytic drug widely used in hemorrhagic trauma patients and cardiovascular, orthopedic, and gynecological surgical patients. TXA binds plasminogen and prevents its maturation to the fibrinolytic enzyme plasmin. A number of studies have demonstrated the broad life‐saving effects of TXA in trauma, superior to those of other antifibrinolytic agents. Besides preventing fibrinolysis and blood loss, TXA has been reported to suppress posttraumatic inflammation and edema. Although the efficiency of TXA transcends simple inhibition of fibrinolysis, little is known about its mechanisms of action besides the suppression of plasmin maturation. Understanding the broader effects of TXA at the cell, organ, and organism levels are required to elucidate its potential mechanisms of action transcending antifibrinolytic activity. In this article, we provide a brief review of the current clinical use of TXA and then focus on the effects of TXA beyond antifibrinolytics such as its anti‐inflammatory activity, protection of the endothelial and epithelial monolayers, stimulation of mitochondrial respiration, and suppression of melanogenesis.

Anti‐fibrinolytic agent tranexamic acid suppresses the endotoxin‐induced expression of Tnfα and Il1α genes in a plasmin‐independent manner

“…An alternative explanation may be that the observed similarity of TXA effects in Plg null and heterozygous mice is due to the inhibition of other proteases besides plasmin. 21 In conclusion, it remains to be determined the molecular mechanisms of plasmin-independent suppression of proinflammatory cytokines genes by TXA. A mass-spectrometry-based search of novel protein targets of TXA could be useful to address this issue.…”

“…The decrease of proinflammatory cytokines expression by TXA may at least partially be explained by its beneficial effects on mitochondria. An alternative explanation may be that the observed similarity of TXA effects in Plg null and heterozygous mice is due to the inhibition of other proteases besides plasmin 21 …”

“…Such an analysis can be of clinical interest. TXA is known to exhibit a number of cell protective and anti-inflammatory effects both in vivo and in vitro, which are not directly related to its recognized clinical function, that is, suppression of fibrinolysis and decrease of blood loss (for review see 21 ). Thus, TXA has been shown to decrease the blood level of TNFα in animal hemorrhagic trauma models 7,9 and in human cardiac surgery patients.…”

Prehospital tranexamic acid is associated with a dose-dependent decrease in syndecan-1 after trauma: A secondary analysis of a prospective randomized trial

“…Tranexamic acid (TXA) in particular has emerged as a useful therapeutic agent to promote hemostasis and to prevent blood loss in injured patients. Prior to its application to trauma, TXA was routinely used in orthopedic, obstetrics and gynecology, and cardiothoracic patients in hospital and surgical settings 5–7 . Most recently, in the Study of Tranexamic Acid During Air and Ground Prehospital Transport (STAAMP) Trial, prehospital TXA was associated with lower mortality in specific subgroups of injured trauma patients who received TXA close to the time of their injuries 3,8,9 .…”

“…Importantly, these results may be sensitive to the dose and timing of TXA administration 15,21 . Tranexamic acid has also been shown to have beneficial effects on vascular permeability, inflammation, and glycocalyx degradation beyond antifibronolysis, highlighting several gaps in our mechanistic understanding of this drug 7 …”