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Title: Profibrinolytic effects of rivaroxaban are mediated by thrombin-activatable fibrinolysis inhibitor and are attenuated by a naturally occurring stabilizing mutation in enzyme. Author: Garabon JJW, Boffa MB. Journal: J Thromb Thrombolysis; 2023 Aug; 56(2):283-290. PubMed ID: 37310666. Abstract: Rivaroxaban is a direct factor Xa inhibitor, recently implemented as a favorable alternative to warfarin in anticoagulation therapy. Rivaroxaban effectively reduces thrombin generation, which plays a major role in the activation of thrombin activatable fibrinolysis inhibitor (TAFI) to TAFIa. Based on the antifibrinolytic role of TAFIa, we hypothesized that rivaroxaban would consequently induce more rapid clot lysis. In vitro clot lysis assays were used to explore this hypothesis and additionally determine the effects of varying TAFI levels and a stabilizing Thr325Ile polymorphism (rs1926447) in the TAFI protein on the effects of rivaroxaban. Rivaroxaban was shown to decrease thrombin generation, resulting in less TAFI activation, thus enhancing lysis. These effects were also shown to be less substantial in the presence of greater TAFI levels or the more stable Ile325 enzyme. These findings suggest a role for TAFI levels and the Thr325Ile polymorphism in the pharmacodynamics and pharmacogenomics of rivaroxaban.[Abstract] [Full Text] [Related] [New Search]