Chatelain, Bernard

Devalet, Bérangère

Dogne, Jean-Michel

Douxfils, Jonathan

Hjemdahl, Paul

Mullier, François

Rönquist-Nii, Yuko

Tamigniau, Anne

Wallemacq, Pierre

English

Repository of the University of Namur

RESEARCH OUTPUTS / RÉSULTATS DE RECHERCHEAuthor(s) - Auteur(s) :Publication date - Date de publication :Permanent link - Permalien :Rights / License - Licence de droit d’auteur :Bibliothèque Universitaire Moretus PlantinInstitutional Repository - Research PortalDépôt Institutionnel - Portail de la Rechercheresearchportal.unamur.beIs Dilute Russell’s Viper Venom Time a Useful Assay To Monitor Patients Treated ByRivaroxaban Or Dabigatran Etexilate?Douxfils, Jonathan; Tamigniau, Anne; Chatelain, Bernard; Devalet, Bérangère; Wallemacq,Pierre; Hjemdahl, Paul; Rönquist-Nii, Yuko; Dogne, Jean-Michel; Mullier, FrançoisPublished in:Blood 2013 122:3634; published ahead of print December 6, 2013Publication date:2013Document VersionPeer reviewed versionLink to publicationCitation for pulished version (HARVARD):Douxfils, J, Tamigniau, A, Chatelain, B, Devalet, B, Wallemacq, P, Hjemdahl, P, Rönquist-Nii, Y, Dogne, J-M &Mullier, F 2013, Is Dilute Russell’s Viper Venom Time a Useful Assay To Monitor Patients Treated ByRivaroxaban Or Dabigatran Etexilate? in Blood 2013 122:3634; published ahead of print December 6, 2013.55th ASH Annual Meeting and Exposition, New Orleans, United States, 7/12/13.General rightsCopyright and moral rights for the publications made accessible in the public portal are retained by the authors and/or other copyright ownersand it is a condition of accessing publications that users recognise and abide by the legal requirements associated with these rights.            • Users may download and print one copy of any publication from the public portal for the purpose of private study or research.            • You may not further distribute the material or use it for any profit-making activity or commercial gain            • You may freely distribute the URL identifying the publication in the public portal ?Take down policyIf you believe that this document breaches copyright please contact us providing details, and we will remove access to the work immediatelyand investigate your claim.Download date: 23. Jun. 2020ResultsMethods.ConclusionsDisclosure ContactJ. Douxfils: jonathan.douxfils@unamur.beJM Dogné: jean-Michel.dogné@unamur.be F. Mullier: mullierfrancois@gmail.com The authors have no relevant conflicts of interest to disclose.ObjectivesDiscussionBackgroundDirect oral anticoagulants (DOACs) include anti-IIa agent(dabigatran etexilate) and anti-Xa agents (rivaroxaban,apixaban and edoxaban). DOACs do not require monitoring norfrequent dose adjustment. However, searching for the optimalresponse at the individual patient level may be useful in somesituations. Activated partial thromboplastin time, HemoclotThrombin Inhibitor® (HTI) and ecarin clotting time have beenproposed to monitor dabigatran whereas anti-Xa chromogenicassays are preferable to monitor anti-Xa agents1,2,3. However,there is still a need for a global test easily implementable andwidely available that may be used for all DOACs. Recentstudies showed that the dilute Russell Viper Venom Time(DRVV-T) could be used for the monitoring of DOACs but theseresults have not been performed on clinical samples4.To analyse and compare the results obtained withSTA®-DRVV Screen and STA®-DRVV Confirm with theplasma drug levels measured by LC-MS/MS.60 plasmas from patients treated with rivaroxaban and 48 plasmas from patients treated with dabigatran etexilatewere included in the study. Plasma concentrations were measured by LC-MS/MS. STA®-DRVV Screen and Confirm (Diagnostica Stago®) were performed on the 108 plasma samples. All methodologies were performed according to the recommendations of the manufacturer.Dilute Russell Viper Venom Time: A Useful Assay for the Monitoring of Direct Oral Anticoagulants in Patients?Jonathan Douxfils1, Anne Tamigniau2, Bernard Chatelain3, Bérangère Devalet3, Pierre Wallemacq2, Paul Hjemdahl4, Yuko Rönquist-Nii4, Jean-Michel Dogné1*, François Mullier1, 3*1 Department of Pharmacy, Namur Thrombosis and Hemostasis Center (NTHC), Namur Research Institute for LIfe Sciences (NARILIS), University of Namur, Belgium2 Laboratory of Clinical Chemistry, Saint-Luc University Hospital, Université Catholique de Louvain, Brussels, Belgium3 Hematology Laboratory, Namur Thrombosis and Hemostasis Center (NTHC), Namur Research Institute for LIfe Sciences (NARILIS), CHU UCL Mont-Godinne-Dinant , Université Catholique de Louvain, Belgium4 Department of Clinical Pharmacology, Karolinska University Hospital and Clinical Pharmacology Unit, Department of Medicine Solna, Karolinska Institutet, SE-171 76 Stockholm, Sweden.- The DRVV cannot be used to accuratelyestimate dabigatran and rivaroxabanplasma concentrations- Specific cut-off could however be proposedto rule out excessive concentrations (i.e.concentrations > 200ng/mL at Ctrough)- However, these cut-offs are specific fordabigatran and rivaroxaban due todifference in sensitivities and also dependon the quantity of phospholipid in the test.STA®-DRVV ScreenFigure 1: Correlation between STA®-DRVVScreen and dabigatran or rivaroxaban plasmaconcentraitons. Results are expressed in seconds(A), as ratio (B) or in ng/mL (C). Graphic of theBland-Altman analysis (D) comparing the twomethods for results expressed in ng/mL is alsoprovided. For the Bland Altman analysis thedifference is calculated as follow: [difference (A-B)vs. average] where A is the result of the LC-MS/MSand B the result of calibrated STA®-DRVV Screen.STA®-DRVV ConfirmFigure 2: Correlation between STA®-DRVVConfirm and dabigatran or rivaroxaban plasmaconcentration. Results are expressed in seconds(A), as ratio (B) or in ng/mL (C). Graphic of theBland-Altman analysis (D) comparing the twomethods for results expressed in ng/mL is alsoprovided. For the Bland Altman analysis thedifference is calculated as follow: [difference (A-B)vs. average] where A is the result of the LC-MS/MSand B the result of calibrated STA®-DRVV Confirm.ResultsDiscussionThe dabigatran plasma concentration ranged from 0 to 413ng/mL and the rivaroxaban plasma concentration ranged from 0 to 426ng/mL.Correlation between STA®-DRVV Screen and LC-MS/MS measurementsCalibrated STA®-DRVV Screen and dabigatran or rivaroxaban plasma concentrations correlate well (Figures 1 C). The Spearman correlation is 0.84 (95% CI: 0.72 – 0.91; p<0.0001) and0.88 (95% CI: 0.82 – 0.93) for dabigatran and rivaroxaban, respectively. When expressed in seconds or as ratios the relation is not linear and is best fit by a second order relation (Figures1 A & B). Results of the Bland-Altman analysis reveal a mean difference of -37ng/mL and -21ng/mL for dabigatran and rivaroxaban, respectively, with large confidence interval.This implies that STA®-DRVV Screen tends to overestimate the concentration of dabigatran and rivaroxaban in plasma samples. Therefore STA®-DRVV Screen should not be used toestimate plasma concentrations of both dabigatran and rivaroxaban. However, specific cut-off associated with supra-therapeutic concentrations at Ctrough (i.e. 200ng/mL which representthe 90th percentile of plasma concentrations at Ctrough) could be defined. Thus, a ratio of 2.5 or 3.0 could exclude plasma concentration above 200ng/mL for dabigatran and rivaroxaban,respectively.Correlation between STA®-DRVV Confirm and LC-MS/MS measurementsCalibrated STA®-DRVV Confirm and dabigatran or rivaroxaban plasma concentrations correlate well (Figures 2 C). The Spearman correlation is 0.94 (95% CI: 0.89 – 0.97; p<0.0001) and0.89 (95% CI: 0.82 – 0.94; p<0.0001) for dabigatran and rivaroxaban, respectively. When expressed in seconds or as ratios the relation is not linear and is best fit by a second orderrelation (Figures 2 A & B). Results of the Bland-Altman analysis reveal a mean difference of -40ng/mL and -16ng/mL with large confidence interval for dabigatran and rivaroxaban,respectively.This implies that STA®-DRVV Confirm tends to overestimate the concentration of dabigatran and rivaroxaban in plasma samples. Therefore STA®-DRVV Confirm should not be used toestimate plasma concentrations of both dabigatran and rivaroxaban. As for STA®-DRVV Screen, specific cut-off could be proposed and a ratio of 1.8 or 2.5 at Ctrough with STA®-DRVVConfirm could exclude supra-therapeutic levels of dabigatran and rivaroxaban, respectively.1  Douxfils J, Mullier F, Robert S, et al. Thromb Haemost 2012 May;107(5):985-97.2 Barrett YC, Wang Z, Frost C, et al. Thromb Haemost 2010 Dec;104(6):1263-71.3 Samama MM, Contant G, Spiro TE, et al. Thromb Haemost 2012 Feb;107(2):379-87.4 Exner T, Ellwood L, Rubie J, Barancewicz A.Thromb Haemost. 2013; 109: 762-5. 5  Douxfils J, Dogné J-M, Mullier F; et al. Thromb Haemost. 2013; 110(3): 543-9 References

Is Dilute Russell’s Viper Venom Time a Useful Assay To Monitor Patients Treated By Rivaroxaban Or Dabigatran Etexilate?

https://pure.unamur.be/ws/files/12251516/ASH_2013_Douxfils_DRVVT_a_useful_assay_for_the_monitoring_of_NOACs.pdf

Is Dilute Russell’s Viper Venom Time a Useful Assay To Monitor Patients Treated By Rivaroxaban Or Dabigatran Etexilate?

Abstract

Similar works

Full text

Available Versions

Repository of the University of Namur