Concomitant assessment of rivaroxaban concentration and its impact on thrombin generation

Saartje Bloemen, Suzanne Zwaveling, François Mullier, Jonathan Douxfils

Research output: Contribution to journalArticle

Abstract

BACKGROUND: Reliable assays to measure direct oral anticoagulant (DOAC) levels and their activity in critical situations are needed. Drug levels alone are not representative of the effect of DOACs on an individual's coagulation. We developed a technique that provides direct assessment of the global effect of rivaroxaban on the individual's coagulation in addition to plasma concentrations.

METHODS: DOAC concentrations were determined in fifty patients using rivaroxaban, with the new assay, Xross-CAT. The effect of rivaroxaban on coagulation (activity) was measured with thrombin generation (TG) in platelet poor plasma using 5 pM tissue factor on the same device. The levels were validated with the Biophen DiXal assay. The prothrombin time (PT) and dilute Russell viper venom time (dRVVT) were performed to estimate the effect on coagulation.

RESULTS: The variability of Xross-CAT was below 12%. Xross-CAT correlates well with Biophen DiXaI (rs = 0.885). The bias, determined by Bland-Altman analysis, was 4.9% and the Passing-Bablok equation was y = 1.1x - 2.1. The correlation of plasma levels with TG was moderate (ETP rs = -0.548; Peak rs = -0.559), as for the PT (rs = 0.739) and the dRVVT (rs = 0.692).

CONCLUSIONS: Xross-CAT shows a good correlation with Biophen DiXaI that was previously confirmed to accurately assess rivaroxaban levels. Bleeding and thrombotic complications are not necessarily associated with drug levels and could be influenced by concomitant risk factors. The main benefit of Xross-CAT is that it can be performed simultaneously with thrombin generation, providing an overview of the global anticoagulation status of a patient in relation to circulating DOAC levels.

Original languageEnglish
Pages (from-to)8-15
Number of pages8
JournalThrombosis Research
Volume184
Early online date2019
DOIs
Publication statusPublished - Dec 2019

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Prothrombin Time
Thrombin
Anticoagulants
Thromboplastin
Pharmaceutical Preparations
Blood Platelets
Hemorrhage
Equipment and Supplies
Rivaroxaban

Keywords

  • Coagulation assays
  • Direct factor Xa inhibitor
  • Plasma concentrations
  • Rivaroxaban
  • Thrombin generation

Cite this

@article{ceff07808f5a43f6a342ed9a7c23128b,
title = "Concomitant assessment of rivaroxaban concentration and its impact on thrombin generation",
abstract = "BACKGROUND: Reliable assays to measure direct oral anticoagulant (DOAC) levels and their activity in critical situations are needed. Drug levels alone are not representative of the effect of DOACs on an individual's coagulation. We developed a technique that provides direct assessment of the global effect of rivaroxaban on the individual's coagulation in addition to plasma concentrations.METHODS: DOAC concentrations were determined in fifty patients using rivaroxaban, with the new assay, Xross-CAT. The effect of rivaroxaban on coagulation (activity) was measured with thrombin generation (TG) in platelet poor plasma using 5 pM tissue factor on the same device. The levels were validated with the Biophen DiXal assay. The prothrombin time (PT) and dilute Russell viper venom time (dRVVT) were performed to estimate the effect on coagulation.RESULTS: The variability of Xross-CAT was below 12{\%}. Xross-CAT correlates well with Biophen DiXaI (rs = 0.885). The bias, determined by Bland-Altman analysis, was 4.9{\%} and the Passing-Bablok equation was y = 1.1x - 2.1. The correlation of plasma levels with TG was moderate (ETP rs = -0.548; Peak rs = -0.559), as for the PT (rs = 0.739) and the dRVVT (rs = 0.692).CONCLUSIONS: Xross-CAT shows a good correlation with Biophen DiXaI that was previously confirmed to accurately assess rivaroxaban levels. Bleeding and thrombotic complications are not necessarily associated with drug levels and could be influenced by concomitant risk factors. The main benefit of Xross-CAT is that it can be performed simultaneously with thrombin generation, providing an overview of the global anticoagulation status of a patient in relation to circulating DOAC levels.",
keywords = "Coagulation assays, Direct factor Xa inhibitor, Plasma concentrations, Rivaroxaban, Thrombin generation",
author = "Saartje Bloemen and Suzanne Zwaveling and Fran{\cc}ois Mullier and Jonathan Douxfils",
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year = "2019",
month = "12",
doi = "10.1016/j.thromres.2019.09.037",
language = "English",
volume = "184",
pages = "8--15",
journal = "Thrombosis Research",
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}

Concomitant assessment of rivaroxaban concentration and its impact on thrombin generation. / Bloemen, Saartje; Zwaveling, Suzanne; Mullier, François; Douxfils, Jonathan.

In: Thrombosis Research, Vol. 184, 12.2019, p. 8-15.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Concomitant assessment of rivaroxaban concentration and its impact on thrombin generation

AU - Bloemen, Saartje

AU - Zwaveling, Suzanne

AU - Mullier, François

AU - Douxfils, Jonathan

N1 - Copyright © 2019 Elsevier Ltd. All rights reserved.

PY - 2019/12

Y1 - 2019/12

N2 - BACKGROUND: Reliable assays to measure direct oral anticoagulant (DOAC) levels and their activity in critical situations are needed. Drug levels alone are not representative of the effect of DOACs on an individual's coagulation. We developed a technique that provides direct assessment of the global effect of rivaroxaban on the individual's coagulation in addition to plasma concentrations.METHODS: DOAC concentrations were determined in fifty patients using rivaroxaban, with the new assay, Xross-CAT. The effect of rivaroxaban on coagulation (activity) was measured with thrombin generation (TG) in platelet poor plasma using 5 pM tissue factor on the same device. The levels were validated with the Biophen DiXal assay. The prothrombin time (PT) and dilute Russell viper venom time (dRVVT) were performed to estimate the effect on coagulation.RESULTS: The variability of Xross-CAT was below 12%. Xross-CAT correlates well with Biophen DiXaI (rs = 0.885). The bias, determined by Bland-Altman analysis, was 4.9% and the Passing-Bablok equation was y = 1.1x - 2.1. The correlation of plasma levels with TG was moderate (ETP rs = -0.548; Peak rs = -0.559), as for the PT (rs = 0.739) and the dRVVT (rs = 0.692).CONCLUSIONS: Xross-CAT shows a good correlation with Biophen DiXaI that was previously confirmed to accurately assess rivaroxaban levels. Bleeding and thrombotic complications are not necessarily associated with drug levels and could be influenced by concomitant risk factors. The main benefit of Xross-CAT is that it can be performed simultaneously with thrombin generation, providing an overview of the global anticoagulation status of a patient in relation to circulating DOAC levels.

AB - BACKGROUND: Reliable assays to measure direct oral anticoagulant (DOAC) levels and their activity in critical situations are needed. Drug levels alone are not representative of the effect of DOACs on an individual's coagulation. We developed a technique that provides direct assessment of the global effect of rivaroxaban on the individual's coagulation in addition to plasma concentrations.METHODS: DOAC concentrations were determined in fifty patients using rivaroxaban, with the new assay, Xross-CAT. The effect of rivaroxaban on coagulation (activity) was measured with thrombin generation (TG) in platelet poor plasma using 5 pM tissue factor on the same device. The levels were validated with the Biophen DiXal assay. The prothrombin time (PT) and dilute Russell viper venom time (dRVVT) were performed to estimate the effect on coagulation.RESULTS: The variability of Xross-CAT was below 12%. Xross-CAT correlates well with Biophen DiXaI (rs = 0.885). The bias, determined by Bland-Altman analysis, was 4.9% and the Passing-Bablok equation was y = 1.1x - 2.1. The correlation of plasma levels with TG was moderate (ETP rs = -0.548; Peak rs = -0.559), as for the PT (rs = 0.739) and the dRVVT (rs = 0.692).CONCLUSIONS: Xross-CAT shows a good correlation with Biophen DiXaI that was previously confirmed to accurately assess rivaroxaban levels. Bleeding and thrombotic complications are not necessarily associated with drug levels and could be influenced by concomitant risk factors. The main benefit of Xross-CAT is that it can be performed simultaneously with thrombin generation, providing an overview of the global anticoagulation status of a patient in relation to circulating DOAC levels.

KW - Coagulation assays

KW - Direct factor Xa inhibitor

KW - Plasma concentrations

KW - Rivaroxaban

KW - Thrombin generation

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DO - 10.1016/j.thromres.2019.09.037

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