Fuente: Biomolecules - Revista científica (MDPI) Biomolecules, Vol. 16, Pages 696: Functional Aspects of Fibrin Structure Alterations by Tranexamic Acid in the Inhibition of Fibrinolysis
Biomolecules doi: 10.3390/biom16050696
Authors:
Kata Balog Virag
Barbara Baráth
Kristóf Molnár
Petra Csikós
Alexandra Raska
László Szabó
Natalia Nikolova
Kiril Tenekedjiev
Krasimir Kolev
Nikolett Wohner

Background: Tranexamic acid (TXA) is a synthetic lysine analog widely used as an antifibrinolytic agent. Large randomized trials have demonstrated life-saving benefits when TXA is administered early in acute hemorrhage, but results regarding prophylactic administration have been conflicting, and several trials have not shown improved clinical outcomes. The mechanisms underlying this discrepancy remain incompletely understood. Objectives: To investigate the molecular and structural mechanisms that determine TXA efficacy in purified fibrin clots under conditions mimicking therapeutic versus prophylactic administration. Methods: We examined fibrinolysis induced by tissue plasminogen activator (tPA) in vitro using confocal microscopy, viscoelastic testing (ClotPro), turbidimetry, and plasmin generation assays at physiologically and therapeutically relevant concentrations of plasminogen and TXA. Scanning electron microscopy (SEM) was employed to assess fibrin structure. Results: When TXA was incorporated into fibrin clots before the addition of tPA, physiological plasminogen concentrations (2.5 µM) reversed the antifibrinolytic effect, resulting in paradoxical acceleration of lysis. By contrast, when clotting and fibrinolysis occurred simultaneously in the presence of TXA and tPA, TXA consistently prolonged lysis time irrespective of plasminogen concentration. SEM demonstrated that TXA, even at concentrations as low as 16 µM, doubled the top-quartile values of the fibrin fiber diameter, altering susceptibility to plasmin-mediated degradation without accelerating plasminogen activation. Conclusions: TXA efficacy is determined not only by dose but also by timing and the plasminogen availability in the clot microenvironment. These findings provide mechanistic insight into the failure of prophylactic TXA administration and highlight the importance of context in optimizing its clinical use.