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Updated: Jun 20, 2025
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Published on: April 19, 2024
Evaluation of thrombomodulin/thrombin activatable fibrinolysis inhibitor function in plasma using tissue-type
Tetsumei Urano1,2, Yoshie Sano1, Yuji Suzuki3
1Department of Medical Physiology, Hamamatsu University School of Medicine, Hamamatsu, Shizuoka, Japan.
Background:
Thrombin activatable fibrinolysis inhibitor (TAFI) is one of the most important physiological fibrinolysis inhibitors. Its inhibitory efficacy under physiological conditions remains uncertain.
Objectives:
Elucidate the role of soluble thrombomodulin (sTM)/TAFI axis in the regulation of fibrinlysis.
Methods:
Since thrombin is required to generate activated TAFI (TAFIa) that targets the C-terminal lysine of partially digested fibrin, a clot lysis assay is suitable for evaluating its function. Using tissue-type plasminogen activator-induced plasma clot lysis time (tPA-PCLT) together with TAFIa inhibitor and recombinant sTM (rsTM), we evaluated the specific function of TM/TAFI in the plasma milieu.
Results:
tPA-PCLT values were significantly shortened by the TAFIa inhibitor. rsTM supplementation prolonged tPA-PCLT, which was shortened by the TAFIa inhibitor to a time similar to that obtained without rsTM and with the TAFIa inhibitor. Plasma obtained from patients treated with rsTM showed prolonged tPA-PCLT, which was shortened by the TAFIa inhibitor but not further prolonged by rsTM. However, no significant correlation was observed between tPA-PCLT and parameters of TM/TAFI system in the plasma.
Conclusion:
The role of the TM/TAFI system in regulating fibrinolysis was successfully evaluated using TAFIa inhibitor and rsTM. Trace amounts of soluble TM in normal plasma appeared sufficient to activate TAFI and inhibit fibrinolysis. Further, a therapeutic dose of rsTM appeared sufficient to activate TAFI and regulate fibrinolysis in the plasma milieu.
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