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Monitoring the roles of prothrombin activation fragment 1 and 2 (F1 + 2) in patients with atrial fibrillation receiving rivaroxaban and apixaban

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Abstract

Factor Xa (FXa) inhibitors are recommended for use in fixed doses without laboratory monitoring. However, prior studies reported the importance of establishing biomarkers representing anticoagulation intensity related to bleeding or thrombotic events. To test the hypothesis that prothrombin activation fragment 1 and 2 (F1 + 2), a non-specific marker of thrombin generation, could be altered during FXa inhibitor treatment in patients with atrial fibrillation. We conducted the study in two different clinical settings. First, the interrelations among biomarkers representing coagulation/fibrinolysis were investigated in 80 patients in an outpatient clinic. Second, these biomarkers were evaluated in 75 patients who underwent radiofrequency catheter ablation. Plasma concentration of FXa inhibitors was evaluated using an anti-FXa chromogenic assay (C-Xa). In the outpatient study, only F1 + 2 exhibited a significant and negative association with C-Xa (rS =  − 0.315, p = 0.026), and 37% of the variance could be explained by C-Xa levels. F1 + 2 levels above the reference range (> 229 pmol/L) could be considered as a cut-off to identify poor patient compliance or under-dosing. In the peri-ablation study, increased F1 + 2 levels were associated with decline of C-Xa levels after periprocedural discontinuation of FXa inhibitors, which was greater in the rivaroxaban group than in the apixaban group. F1 + 2 showed modest and inverse association with plasma concentration of rivaroxaban and apixaban in patients with atrial fibrillation. Larger study to test the hypothesis that continued thrombin generation despite anticoagulation is associated with a heightened risk of clinical events is required.

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Funding

This work was supported by funds from the Vehicle Racing Commemorative Foundation (2013–2015), a Grant for Collaborative Research from Kanazawa Medical University (C2015-4), and a Grant-in-Aid for Scientific Research (C) (Grant Number: JP25460661) to Dr. Kouji Kajinami.

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Authors and Affiliations

  1. Department of Cardiology, Kanazawa Medical University, 1-1 Daigaku, Uchinada, 920-0293, Japan

    Ei-ichi Ueno, Kosuke Fujibayashi, Jun Sawaguchi, Yushi Yasuda, Shintaro Takano, Nakaba Fujioka, Yasuyuki Kawai & Kouji Kajinami

  2. Central Clinical Laboratoy, Kanazawa Medical University Hospital, 1-1 Daigaku, Uchinada, 920-0293, Japan

    Harumi Fujita & Yoshi Tanaka

Authors
  1. Ei-ichi Ueno
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  2. Kosuke Fujibayashi
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  3. Jun Sawaguchi
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  4. Yushi Yasuda
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  5. Shintaro Takano
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  6. Nakaba Fujioka
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  7. Yasuyuki Kawai
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  8. Harumi Fujita
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  9. Yoshi Tanaka
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  10. Kouji Kajinami
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Correspondence to Kosuke Fujibayashi.

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Ueno, Ei., Fujibayashi, K., Sawaguchi, J. et al. Monitoring the roles of prothrombin activation fragment 1 and 2 (F1 + 2) in patients with atrial fibrillation receiving rivaroxaban and apixaban. J Thromb Thrombolysis 50, 371–379 (2020). https://doi.org/10.1007/s11239-020-02079-7

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