Rivaroxaban and apixaban induce clotting factor Xa fibrinolytic activity

Carter, R. L. R.; Talbot, Kimberley; Hur, Woosuk Steve; Meixner, Scott C.; Gugten, J. Grace van der; Holmes, Daniel T.; Côté, Hélène; Kastrup, Christian J.; Smith, Tyler; Lee, A. Y. Y.; Pryzdial, Edward L. G.

doi:10.1111/jth.14281

Cited by 38 publications

(37 citation statements)

References 49 publications

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“…34 Direct inhibition of factor X induced by rivaroxaban and consequently decreased thrombin formation could favorably affect fibrin clot structure and susceptibility to lysis, as demonstrated previously. 19, 35,36 We confirmed that the rivaroxaban concentration is strongly positively correlated with K s and negatively with CLT. Importantly, our findings suggest that the modulation of fibrin clot properties by rivaroxaban cannot suppress the association of K s with recurrent VTE, as demonstrated previously among patients with VTE who stopped anticoagulation.…”

Section: Follow -Upsupporting

confidence: 65%

Plasma clot permeability and lysability determined on rivaroxaban and clinical outcomes in patients with venous thromboembolism: a cohort study

Frączek¹,

Krzysztofik²,

Stanisz³

et al. 2019

Polish Archives of Internal Medicine

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INTRODUCTION Venous thromboembolism (VTE), including deep vein thrombosis (DVT) and pulmonary embolism (PE), afflicts over 1 million people in Europe annually. 1 The 1-year incidence of recurrent VTE is approximately 2% among patients receiving direct oral anticoagulants (DOACs) or vitamin K antagonists (VKAs), 2 and rises to 11% at 1 year and 30% at 5 years among individuals following unprovoked VTE after cessation of anticoagulation. 3 The main established risk factors predisposing to VTE recurrence include older age, male sex, high body mass index (BMI), active cancer, unprovoked VTE, proximal DVT or PE, antiphospholipid antibody syndrome, short duration of anticoagulant

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Section: Follow -Upsupporting

confidence: 65%

Plasma clot permeability and lysability determined on rivaroxaban and clinical outcomes in patients with venous thromboembolism: a cohort study

Frączek¹,

Krzysztofik²,

Stanisz³

et al. 2019

Polish Archives of Internal Medicine

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“…While most of previous studies demonstrated promotive effects of DOACs on fibrinolysis, the effects on fibrinolysis observed by CFWA were seemingly complicated in the present study . Roughly, promotive effects represented by increased Max n 1 and/or shortened fibrinolysis peak time were observed at high concentrations of rivaroxaban and dabigatran while suppressive effects represented by decreased Max n 1 and/or prolonged fibrinolysis peak time were observed at low concentrations of them.…”

Section: Discussioncontrasting

confidence: 54%

Section: Discussionmentioning

confidence: 99%

“…5 A number of reports have provided several lines of evidence for enhancement of fibrinolysis by DOACs, suggesting its potential contribution to the therapeutic efficacy and bleeding risk. [6][7][8] For understanding of laboratory aspects of the pharmacological effects, it would be better to assess such influence of DOACs on fibrinolysis with techniques for use in routine laboratories. More recently, clot-fibrinolysis waveform analysis (CFWA) has been developed by Nogami and his colleagues as an automated technique to simultaneously evaluate both clot and fibrinolysis, which seems acceptable to routine laboratories handling APTT and PT.…”

Section: Introductionmentioning

confidence: 99%

“…A number of reports have provided several lines of evidence for enhancement of fibrinolysis by DOACs, suggesting its potential contribution to the therapeutic efficacy and bleeding risk . For understanding of laboratory aspects of the pharmacological effects, it would be better to assess such influence of DOACs on fibrinolysis with techniques for use in routine laboratories.…”

Section: Introductionmentioning

confidence: 99%

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Application of clot‐fibrinolysis waveform analysis to assessment of in vitro effects of direct oral anticoagulants on fibrinolysis

Oka

Wakui

Fujimori

et al. 2020

Int J Lab Hematology

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Introduction: Acceleration of fibrinolysis by direct oral anticoagulants (DOACs) has been reported by several groups, suggesting contribution of not only anticoagulant but also fibrinolytic effects to the therapeutic efficacy. The present study aims to evaluate the usability of clot-fibrinolysis waveform analysis (CFWA) for assessment of in vitro effects of DOACs on fibrinolysis. Methods:The experimental conditions were optimized according to how t-PA concentrations and a time length after t-PA adjustment affect parameters of CFWA.Addition of the activated partial thromboplastin time (APTT) reagent followed by that of calcium and t-PA was done to obtain clotting and fibrinolytic reaction curves which were mathematically differentiated for CFWA (APTT-CFWA). The positive and negative modes of waveforms were defined as the direction toward fibrin generation and that toward fibrin degradation, respectively. The maximum positive and negative values (Max p 1 and Max n 1) correspond to the maximum coagulation velocity and the maximum fibrinolysis velocity, respectively. Plasma spiked with each of DOACs (rivaroxaban, apixaban, edoxaban, and dabigatran) was subjected to APTT-CFWA.Results: Optimization of t-PA use was based on Max n 1. Roughly biphasic effects of rivaroxaban and dabigatran but not apixaban or edoxaban on fibrinolysis were observed through Max n 1 and the fibrinolysis peak time, which was defined as a time length from the time when Max p 1 (Max p 1 time) to the time when Max n 1 appears (Max n 1 time). Conclusion:The results suggest the usability of CFWA for assessment of DOAC effects and provide insights into relevance of anticoagulation to therapeutic efficacy and bleeding risk from the perspective of fibrinolysis. K E Y W O R D Sactivated partial thromboplastin time, clot-fibrinolysis waveform analysis, direct oral anticoagulants, maximum fibrinolysis velocity, tissue plasminogen activator

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Reproductive issues in women on direct oral anticoagulants

Beyer‐Westendorf

Marten

2021

Research and Practice in Thrombosis and Haemostasis

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Direct oral anticoagulants (DOACs) are replacing warfarin and other vitamin K antagonists for a wide range of indications. Advantages of DOAC therapy are fewer food and drug interactions and fixed dosing without routine laboratory monitoring, making DOACs the perfect choice especially for younger patients, in whom the main indication for anticoagulation is prevention and treatment of venous thromboembolism (VTE). Although DOACs are safer and much more convenient than other anticoagulant alternatives, their profile may have drawbacks, especially for younger female patients in whom reproductive issues need special considerations. These may include the issue of heavy menstrual bleeding (HMB) during anticoagulant therapy, the embryotoxicity risk from inadvertent DOAC exposure during pregnancy, and the prevention or planning of pregnancies during DOAC therapy. This review summarizes the most relevant evidence in this increasingly important field of women’s health.

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Rivaroxaban and apixaban induce clotting factor Xa fibrinolytic activity

Abstract: The current study suggests a previously unknown effect of DOACs on FXa in addition to their well-documented anticoagulant role. By enabling the t-PA cofactor function of FXaβ in plasma, DOACs also enhance fibrinolysis. This effect may broaden their therapeutic indications.

Cited by 38 publications

References 49 publications

Plasma clot permeability and lysability determined on rivaroxaban and clinical outcomes in patients with venous thromboembolism: a cohort study

Plasma clot permeability and lysability determined on rivaroxaban and clinical outcomes in patients with venous thromboembolism: a cohort study

Application of clot‐fibrinolysis waveform analysis to assessment of in vitro effects of direct oral anticoagulants on fibrinolysis

Reproductive issues in women on direct oral anticoagulants

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