Dogne, Jean-Michel

Douxfils, Jonathan

Mullier, François

Raphaël, Mélanie

Sabor, Lina

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.beHeparin Calibrated Anti-Xa Assays for the Measurement of Low Levels of Direct FactorXa InhibitorsSabor, Lina; Raphaël, Mélanie; Dogne, Jean-Michel; Mullier, François; Douxfils, JonathanPublished 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):Sabor, L, Raphaël, M, Dogne, J-M, Mullier, F & Douxfils, J 2017, Heparin Calibrated Anti-Xa Assays for theMeasurement of Low Levels of Direct Factor Xa Inhibitors. in Research and practice in thrombosis andhaemostasis: Abstracts of the XXVI Congress of the International Society on Thrombosis and Haemostasis, July8–13, 2017. vol. 1, pp. 1044, XXVI Congress of the International Society on Thrombosis 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. 20201044  |    PB 2151 | Heparin Calibrated Anti-Xa Assays for the Measurement of Low Levels of Direct Factor Xa InhibitorsL. Sabor1, M. Raphaël2, J.-M. Dogné2, F. Mullier2, J. Douxfils21CHU UCL Namur, Namur Thrombosis and Hemostasis Center (NTHC), Université Catholique de Louvain, Hematology Laboratory, Yvoir, Belgium, 2University of Namur, Namur Thrombosis and Hemostasis Center (NTHC), Department of Pharmacy, Namur, BelgiumBackground: Apixaban, edoxaban and rivaroxaban do not require fre-quent monitoring but an assessment of the intensity of anticoagula-tion may be required in emergent or elective surgery. Some experts reported that anti-Xa activity below 0.1 IU/mL using heparin cali-brated chromogenic assays may assert the absence of clinically rele-vant (i.e. < 30 or < 50 ng/mL depending on the clinical situation) direct factor Xa levels. However, it is not clear if difference in response will depend on the anti-Xa agent and also on the chromogenic anti-Xa kit used to assess the anti-Xa activity.Aims: To assess if a cut-off of 0.1 UI anti-Xa/mL is able to exclude apixaban, rivaroxaban or edoxaban concentration < 30 ng/mL or < 50 ng/mL using different heparin calibrated chromogenic anti-Xa kits.Methods: Apixaban, edoxaban and rivaroxaban were added to normal pooled plasma at increasing concentrations ranging from 0 to 500 ng/mL. Anti-Xa activities were measured using (1) STA®-Liquid Anti-Xa (STA®LAX) on a STA-R Evolution Coagulometer, (2) Biophen®Heparin LRT (BP®LRT) on a STA-R Evolution coagulom-eter and (3) HemosIL®-Liquid Anti-Xa (IL®LAX) on a ACL-TOP 700 according to manufacturer recommendations.Results: At 30 ng/mL of rivaroxaban, BP®LRT, STA®LAX and IL®LAX provided anti-Xa results >0.1 IU/mL. At 30 ng/mL of apixaban or edoxaban, BP®LRT and IL®LAX were below the cut-off but the STA®LAX was not. At a concentration of 50 ng/mL, only edoxaban with the BP®LRT kit showed an anti-Xa activity < 0.1 UI/mL. Conclusions: Low (< 0.1 IU/mL) anti-Xa activity is not safe to exclude clinically relevant direct factor Xa levels and should be avoided. It can only inform if the drug is present or not. Chromogenic anti-Xa assays calibrated against the appropriate agent and using the appropriate procedure remains the more accurate method to assess accurately low levels of direct FXa inhibitors. PB 2152 | Efficacy of a Novel Contact Pathway Inhibitor, Ir-CPI, on in vitro Clotting Induced by PCI Catheter SegmentJ. Douxfils1, D. Gheldof1, S. Derochette2, J. Tassignon2, C. Meinguet2, M. Guyaux2, J.-M. Dogné1, E. Godfroid21University of Namur, Pharmacy, Namur, Belgium, 2Bioxodes, Marche-en-Famenne, BelgiumBackground: Ir-CPI, a protein derived from the tick Ixodes ricinus sali-vary, is a serine protease inhibitor of both factor XIa (FXIa) and FXIIa. In patients undergoing percutaneous coronary intervention (PCI), cath-eter thrombosis may occur as catheters trigger activation of FXII/FXI.Aims: The aim of this study was to evaluate the effect of Ir-CPI on in vitro clotting induced by PCI catheter segment.Methods: Catheter segments were pressed flat, shaped into rings and placed around the perimeter of wells (96-well plate), leaving the center of the well unobstructed. To the wells were added serial dilu-tion of Ir-CPI (until 10 μM) with normal pooled plasma (NPP) or plas-mas deficient in FXI or FXII. After incubation at 37°C and addition of a CaCl2 solution, clot formation was assessed by monitoring absorbance at 340nm. Time to reach one-half maximal absorbance (IC50) was de-fined as the clotting time. Thrombin generation test (TGT) was also assessed using catheter segment as trigger of the process. Positive inhibitory controls were used (fondaparinux, enoxaparin).Results: Presence of the catheter reduced the clotting time of NPP; an effect reversed by the addition of Ir-CPI. At high concentrations (≥ 5μM), Ir-CPI allowed to overpass the clotting time without cath-eter. On TGT (Fig 1), catheter segments decreased lag time and time T A B L E  1 Anti-Xa activities using STA®LAX on a STA-R Evolution Coagulometer, BP®LRT on a STA-R Evolution coagulometer and (3) IL®LAX on a ACL-TOP 700concentra-tion (ng/mL) anticoagulantSTA®LAX (UI/mL)BP®LRT(UI/mL)IL®LAX(UI/mL)30 Rivavoxaban 0,19 0,12 0,0830 Apixaban 0,09 0,03 0,0430 Endoxaban 0,07 0,02 0,0250 Rivavoxaban 0,45 0,34 0,1650 Apixaban 0,17 0,10 0,0750 Endoxaban 0,13 0,06 0,04F I G U R E  1 Effect of Ir-CPI on Thrombin Generation Time (TGT) in NPP exposed to PCI catheter segments

Heparin Calibrated Anti-Xa Assays for the Measurement of Low Levels of Direct Factor Xa Inhibitors

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Heparin Calibrated Anti-Xa Assays for the Measurement of Low Levels of Direct Factor Xa Inhibitors

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