%0 Journal Article
%T Evaluation of thrombomodulin/thrombin activatable fibrinolysis inhibitor function in plasma using tissue-type plasminogen activator-induced plasma clot lysis time.
%A Urano T
%A Sano Y
%A Suzuki Y
%A Okada M
%A Sano H
%A Honkura N
%A Morooka N
%A Doi M
%A Suzuki Y
%J Res Pract Thromb Haemost
%V 8
%N 4
%D 2024 May
%M 39026660
%F 5.953
%R 10.1016/j.rpth.2024.102463
%X <B>UNASSIGNED: </B>Thrombin activatable fibrinolysis inhibitor (TAFI) is one of the most important physiological fibrinolysis inhibitors. Its inhibitory efficacy under physiological conditions remains uncertain.<BR><B>UNASSIGNED: </B>Elucidate the role of soluble thrombomodulin (sTM)/TAFI axis in the regulation of fibrinlysis.<BR><B>UNASSIGNED: </B>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.<BR><B>UNASSIGNED: </B>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.<BR><B>UNASSIGNED: </B>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.