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Tytuł pozycji:

Prolongation of clot lysis time by a direct thrombin inhibitor melagatran mediated by paradoxical enhancement of thrombin generation: comparison with a direct factor Xa inhibitor edoxaban.

Tytuł :
Prolongation of clot lysis time by a direct thrombin inhibitor melagatran mediated by paradoxical enhancement of thrombin generation: comparison with a direct factor Xa inhibitor edoxaban.
Autorzy :
Morishima Y; Biological Research Laboratories, R & D Division, Daiichi Sankyo Co., Ltd, Tokyo, Japan.
Kamisato C
Honda Y
Pokaż więcej
Źródło :
Blood coagulation & fibrinolysis : an international journal in haemostasis and thrombosis [Blood Coagul Fibrinolysis] 2021 Apr 01; Vol. 32 (3), pp. 209-215.
Typ publikacji :
Journal Article
Język :
English
Imprint Name(s) :
Publication: London : Lippincott Williams And Wilkins
Original Publication: Oxford, UK : Rapid Communications of Oxford Ltd., c1990-
References :
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Entry Date(s) :
Date Created: 20210209 Latest Revision: 20210423
Update Code :
20210423
DOI :
10.1097/MBC.0000000000001020
PMID :
33560005
Czasopismo naukowe
Previously, we reported that a direct thrombin inhibitor melagatran paradoxically increased thrombin generation in human plasma in the presence of thrombomodulin. The aim of this study is to test the hypothesis that melagatran may exert a deleterious effect on tissue-type plasminogen activator (t-PA)-induced fibrinolysis via enhancement of thrombin generation and subsequent activation of thrombin-activatable fibrinolysis inhibitor (TAFI) and factor XIII (FXIII). Clot formation in human plasma containing t-PA and thrombomodulin was induced by tissue factor. The absorbance at 405 nm was measured to obtain clot lysis time. Effects of melagatran and a factor Xa inhibitor edoxaban on clot lysis time were determined. In the presence of thrombomodulin, melagatran significantly prolonged clot lysis time, but edoxaban shortened it. In the absence of thrombomodulin, melagatran did not inhibit fibrinolysis. Prolongation of clot lysis time by melagatran was reversed by activated protein C (which suppressed thrombin generation increased by melagatran) and a TAFIa inhibitor. Melagatran significantly suppressed plasmin generation, while edoxaban significantly increased it. However, both melagatran and edoxaban suppressed FXIII activation. In the clot formed in the presence of melagatran and edoxaban, the fibrin fibre was thin compared with control, showing no clear difference in the clot structures between melagatran and edoxaban. These results indicated that melagatran, not edoxaban, prolonged clot lysis time through the paradoxical enhancement of thrombin generation, and subsequent TAFI activation and inhibition of plasmin generation. Neither FXIII activation nor change in fibrin clot structure contributed to the inhibition of fibrinolysis by melagatran.
(Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

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