High-Dose Tranexamic Acid Enhances Circulating Neutrophil Extracellular Traps and Thrombus in Thrombosis Mouse Model

Area of Science:

• Thrombosis research
• Pharmacology
• Hematology

Background:

• Tranexamic acid (TXA) is used to reduce mortality in massive hemorrhage by inhibiting fibrinolysis.
• However, TXA is associated with an increased risk of thrombosis.
• Neutrophil extracellular traps (NETs) activation is implicated in thrombosis formation.

Purpose of the Study:

• To investigate the effects of tranexamic acid (TXA) on circulating and localized NETs, neutrophils, platelets, and vascular endothelium.
• To evaluate the dose-dependent effects of TXA on thrombosis markers in a mouse model.

Main Methods:

• A ferric chloride-induced thrombosis mouse model was utilized.
• Mice received varying doses of TXA (5, 10, 20, 30 mg/kg) or phosphate-buffered saline (PBS).
• Markers of NETs, neutrophils, platelets, endothelial cells, fibrinogen, and D-dimer were analyzed using flow cytometry, immunohistofluorescence, and Western blot.

Main Results:

• Circulating anti-MPO antibody expression was significantly higher in TXA 20 and TXA 30 mg/kg groups.
• D-dimer and anti-fibrinogen antibody expression were lower in TXA 5, 10, and 20 mg/kg groups but higher in the TXA 30 mg/kg group compared to controls.
• No significant differences in anti-Ly6B.2, anti-fibrinogen, and anti-CD31 antibodies were observed across groups.

Conclusions:

• High-dose TXA (30 mg/kg) may increase circulating NETs and localized D-dimer, suggesting a higher thrombosis potential.
• The prothrombotic effects of TXA appear to be dose-dependent.
• Careful dosage adjustment of TXA is recommended, particularly for patients at risk of thrombosis.