Frontiers in immunology · 2026
Cell-dependent antithrombotic effect of tranexamic acid.
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Balog Virág Kata, Csikós Petra, Raska Alexandra, Baráth Barbara, Molnár Kristóf, Nikolova Natalia, Tenekedjiev Kiril, Kolev Krasimir, Wohner Nikolett
Аннотация
BACKGROUND: Tranexamic acid (TXA) is a synthetic lysine analog that inhibits fibrinolysis by blocking lysine-binding sites on plasminogen and plasmin. Although early therapeutic TXA reduces bleeding mortality in major trials, prophylactic benefit appears context- and timing-dependent. TXA is generally not associated with increased thromboembolism, yet its net effect on thrombus formation remains uncertain. Because plasmin(ogen) also acts on leukocytes, endothelium and platelets via cell-surface receptors, TXA may exert cell-dependent effects beyond antifibrinolysis.
OBJECTIVES: To determine how cellular elements modulate TXA's impact on thrombus formation.
METHODS: We studied TXA in an in vivo murine venous thrombosis model without endothelial injury (IVC stenosis). Plasma VWF: Ag and MCP-1 were measured by ELISA. Thrombin generation was assessed in whole blood and plasma-based systems to evaluate cell dependence. Leukocyte-associated plasminogen activation was quantified using plasmin generation assays in fibrin. Primary hemostasis was assessed by tail bleeding.
RESULTS: TXA reduced the odds of venous thrombus formation by 90% but did not alter thrombus mass once clots formed. VWF: Ag remained unchanged, whereas the stenosis-induced rise in MCP-1 was largely suppressed by TXA. TXA decreased thrombin generation in whole blood but not in platelet-rich plasma, indicating a cellular requirement. Consistently, TXA markedly inhibited leukocyte surface-mediated plasminogen activation within fibrin clots. Tail bleeding was unaffected.
CONCLUSION: TXA was not prothrombotic in venous stasis; it reduced thrombus initiation without impairing primary hemostasis. We show for the first time that TXA modulates thrombin generation in a cellular environment, consistent with inhibition of leukocyte-associated plasmin activity.
OBJECTIVES: To determine how cellular elements modulate TXA's impact on thrombus formation.
METHODS: We studied TXA in an in vivo murine venous thrombosis model without endothelial injury (IVC stenosis). Plasma VWF: Ag and MCP-1 were measured by ELISA. Thrombin generation was assessed in whole blood and plasma-based systems to evaluate cell dependence. Leukocyte-associated plasminogen activation was quantified using plasmin generation assays in fibrin. Primary hemostasis was assessed by tail bleeding.
RESULTS: TXA reduced the odds of venous thrombus formation by 90% but did not alter thrombus mass once clots formed. VWF: Ag remained unchanged, whereas the stenosis-induced rise in MCP-1 was largely suppressed by TXA. TXA decreased thrombin generation in whole blood but not in platelet-rich plasma, indicating a cellular requirement. Consistently, TXA markedly inhibited leukocyte surface-mediated plasminogen activation within fibrin clots. Tail bleeding was unaffected.
CONCLUSION: TXA was not prothrombotic in venous stasis; it reduced thrombus initiation without impairing primary hemostasis. We show for the first time that TXA modulates thrombin generation in a cellular environment, consistent with inhibition of leukocyte-associated plasmin activity.