PB0782 - Monocyte-dependent antithrombotic effect of tranexamic acid

Background: 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.

Methods: Thrombus 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(s): 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.