Bloemen, Saartje

de Laat, Bas

Douxfils, Jonathan

Hemker, Hendrick Coenraad

Kremers, Romy

Mullier, François

Peters, T.

Roest, Mark

Wagenvoord, Rob

Zwaveling, Suzanne

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.beA New Method for Determining Concentrations of Direct Oral AnticoagulantsBloemen, Saartje; Zwaveling, Suzanne; Douxfils, Jonathan; Peters, T.; Wagenvoord, Rob;Hemker, Hendrick Coenraad; Mullier, François; de Laat, Bas; Roest, Mark; Kremers, RomyPublished in:Research and practice in thrombosis and haemostasisPublication date:2017Document VersionPublisher's PDF, also known as Version of recordLink to publicationCitation for pulished version (HARVARD):Bloemen, S, Zwaveling, S, Douxfils, J, Peters, T, Wagenvoord, R, Hemker, HC, Mullier, F, de Laat, B, Roest, M& Kr mers, R 2017, A New Method for Determining Concentrations of Direct Oral Anticoagulants. in Researchand practice in thrombosis and haemostasis: Abstracts of the XXVI Congress of the International Society onThrombosis and Haemostasis, July 8–13, 2017. vol. 1, pp. 968, XXVI Congress of the International Society onThrombosis and Haemostasis, Berlin, Germany, 8/07/17.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. 2020968  |    PB 1199 | A New Method for Determining Concentrations of Direct Oral AnticoagulantsS. Bloemen1,2, S. Zwaveling1,2, J. Douxfils3, T. Peters1,2, R. Wagenvoord1,2, H.C. Hemker1,2, F. Mullier3,4, B. de Laat1,2, M. Roest1,2, R. Kremers1,21Synapse Research Institute, CARIM, Maastricht University, Maastricht, The Netherlands, 2CARIM, Maastricht University, Department of Biochemistry, Maastricht, The Netherlands, 3Namur Research Institute for Life Sciences, University of Namur, Department of Pharmacy, Namur, Belgium, 4Université Catholique de Louvain, CHU UCL Namur, Hematology Laboratory, Namur Thrombosis and Hemostasis Center, Yvoir, BelgiumBackground: Direct oral anticoagulants (DOACs) are commonly pro-vided without monitoring. However, reliable assays to measure DOAC levels and activity in emergency situations are needed. We developed a test based on the inhibition of α2macroglobulin-thrombin (α2M-IIa) by dabigatran (DAB) and of α2M-factor Xa (α2M-Xa) by rivaroxaban (RIV), making it possible to evaluate both DOAC classes in combina-tion with thrombin generation (TG).Aims: To quantify DOAC levels and activity in plasma.Methods: Consenting patients using RIV (n=50) and DAB (n=28) were included. TG was performed in platelet poor plasma (5 pM tissue factor), with idarucizumab in calibrator wells for DAB sam-ples. The new DOAC assays measured the effect of diluted plasma samples on Z-Gly-Gly-Arg-AMC conversion by α2M-Xa or α2M-IIa. The slopes of these curves were compared to a reference curve with known DOAC concentrations. DOAC levels were also esti-mated by ‘classical’ assays. Spearman correlation coefficients were determined.Results: A concentration of 30 nM α2M-Xa or α2M-IIa was optimal to measure 50-500 nM RIV/DAB and 90 nM α2M-Xa or 70 nM α2M-IIa, respectively were optimal for 500-1000 nM RIV/DAB (Fig.1).The intra- and inter-assay CV were below 2.5 % and 5% (n=2). Both the RIV and DAB assay correlated with TG parameters. The RIV assay correlated with ‚classical’ assays and had a very good corre-lation with Biophen DiXaI. The DAB assay did not correlate with hemoclot thrombin inhibitor (probably since DAB concentrations were too low), but showed variable correlation with the other as-says (Table1).Conclusions: The new DOAC assays show good correlations with other assays that were confirmed to accurately assess DOAC levels (particularly the RIV assay with the Biophen DiXaI, which had the best correlation with mass spectrometry). Our assay can simultaneously evaluate DOAC concentrations as well as the DOACs effect on thrombin generation, providing an overview of the anticoagulation status of a patient in relation to circulating DOAC levels. F I G U R E  1 Dose-response of several DOAC concentrations at chosen α2M-Xa and α2M-IIa concentrationsT A B L E  1 Correlation (Spearman) of rivaroxaban or dabigatran concentration (as determined by the new assay) with TG and other calibrated assays AssayCorrelation coefficient p-value  AssayCorrelation coefficient p-valueRivaroxaban Calibrated prothrom-bin time (ng/ml)0.468 0.002 Dabigatran Activated partial thrombo-plastin time (s)0.581 0.002 Dilute Russel viper venom time (s)0.760 0.000  Dilute Russel viper venom time (s)0.649 0.001 Biophen DiXaI (ng/ml) 0.915 0.000  Hemoclot thrombin inhibitor (ng/ml)0.391 0.097 TG endogenous thrombin potential(nM.min)-0.525 0.000  Ecarin chromogenic assay (ng/ml)0.591 0.001 TG Peak (nM) -0.550 0.000  TG endogenous thrombin potential(nM.min)-0.323 0.100 TG lag time (min) 0.671 0.000  TG Peak (nM) -0.354 0.201 TG time-to-peak (min) 0.702 0.000  TG lag time (min) 0.423 0.028     TG time-to-peak (min) 0.339 0.084

A New Method for Determining Concentrations of Direct Oral Anticoagulants

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A New Method for Determining Concentrations of Direct Oral Anticoagulants

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