Date of Award

2016

Degree Type

Thesis

Degree Name

M.Sc.

Department

Chemistry and Biochemistry

First Advisor

Boffa, Michael

Keywords

Fibrinolysis, Rivaroxaban, TAFI

Rights

CC BY-NC-ND 4.0

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). Activated TAFI (TAFIa) has an antifibrinolytic role and therefore we hypothesized that rivaroxaban would induce more rapid clot lysis. In vitro clot lysis assays were used to explore this hypothesis. Additionally, these assays were used to determine if the profibrinolytic effects of rivaroxaban could be modulated by TAFI levels or a stabilizing T325I TAFI polymorphism. 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 I325 protein. These findings suggest a role for TAFI levels and the T325I polymorphism in the pharmacodynamics and pharmacogenomics of rivaroxaban.

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