PhD Scientific Days 2026

Molecular Medicine 2.

Functional Aspects of Fibrin Structure Alterations by Tranexamic Acid in the Inhibition of Fibrinolysis

Name of the presenter

Balog Virág, Kata

Institute/workplace of the presenter

Semmelweis University, Department of Biochemistry

Authors

Kata Balog Virág¹, Barbara Baráth¹, Kristóf Molnár¹, Petra Csikós¹, Alexandra Raska¹, László Szabó¹, Krasimir Kolev¹, Nikolett Wohner¹
1: Semmelweis University, Department of Biochemistry

Text of the abstract

Introduction
Tranexamic acid (TXA) is a synthetic lysine analogue widely used as an antifibrinolytic agent. Large randomized trials have demonstrated life-saving benefit when TXA is administered early in acute hemorrhage, but prophylactic administration has repeatedly failed to improve clinical outcomes. The mechanisms underlying this discrepancy remain incompletely understood.
Aim
To investigate the molecular and structural mechanisms that determine TXA efficacy 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 plasminogen and TXA concentrations. 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 into paradoxical acceleration of lysis (lysis rate was 1182 ± 24 µm/h without TXA vs. 1488 ± 48 µm/h with TXA). 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 applying TXA at 64 µM concentration doubled the top-quartile values of the fibrin fiber diameter (108.5 nm vs. 228.3 nm), altering susceptibility to plasmin-mediated degradation without accelerating plasminogen activation.
Conclusion
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.
Funding
HCEMM