PhD Scientific Days 2025

Molecular Medicine I.

Monocyte-dependent Antithrombotic Effect of Tranexamic Acid

Name of the presenter

Balog Virág Kata

Institute/workplace of the presenter

Semmelweis University, Department of Biochemistry

Authors

Kata Balog Virág¹, Alexandra Raska¹, Krisztián Bálint¹, Petra Csikós¹, Krasimir Kolev¹, Nikolett Wohner¹

1: Semmelweis University, Department of Biochemistry

Text of the abstract

Introduction
Tranexamic acid (TXA) is a widespread antifibrinolytic drug that effectively decreases bleeding. Its usage is common in surgical, obstetrical and gynecological procedures, as well as in hematological conditions with a risk of bleeding. Despite being an antifibrinolytic agent, TXA does not increase the risk for thrombosis, and according to some clinical studies, it reduces the prevalence of myocardial infarction.
Aims
To assess the effects of TXA on thrombus formation in vivo and blood coagulation in vitro.
Method
Thrombus formation was induced with inferior vena cava (IVC) stenosis in C57BL/6J mice. After 48-or 72-hours thrombi were retrieved and their weight and length determined. Some mice received 20 µg TXA intramuscularly 24 and 48 hours after IVC stenosis. Na-citrate anticoagulated blood was collected from the retroorbital plexus when thrombi were retrieved. Thrombin generation was measured in diluted whole blood, whereas von Willebrand factor antigen (VWF:Ag) and monocyte chemoattractant protein 1 (MCP-1) were measured in plasma samples.
Results
Thrombus weight was 14.6[9.5; 19]mg at 48 hours and 25.9[14.75; 31.25]mg at 72 hours, whereas their length was 4.9[4;6]mm and 7.22[6;9.5] mm, (median[bottom;top quartile],n=10), respectively. Thrombi were observed in 79% of untreated mice and in 27% of TXA-treated animals. Plasma MCP-1 was 157.3±46.6 pg/mL after IVC stenosis without TXA treatment and 29.8±9.3 pg/mL in TXA-treated mice (mean±SD, n=15), whereas the baseline MCP-1 level was 22.1±5.6 pg/mL in mice not exposed to IVC stenosis. IVC stenosis did not result in any significant difference in plasma VWF:Ag levels (97.6±36.1% vs. 120.7±18.6% in control). TXA-treatment after IVC stenosis significantly suppressed thrombin generation in diluted whole blood (2.7±1.5 RU/s vs. 15.1±2.2 RU/s in the absence of TXA-treatment).
Conclusion
TXA attenuates the formation of IVC stenosis-thrombi in mice. Our in vitro results suggest that this unusual effect of TXA may be caused by the inhibition of monocyte-dependent thrombin generation.
Funding
This project has received funding from the EU’s Horizon 2020 research and innovation program under grant agreement No 739593 and won an EKÖP grant (EKÖP-2024-221/274).