Bouvy, Céline

Douxfils, Jonathan

Evrard, Jonathan

Gheldof, Damien

Mullier, François

Siriez, Romain

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.beRemoval of DOACs from plasmaBouvy, Céline; Evrard, Jonathan; Siriez, Romain; Mullier, François; Douxfils, Jonathan;Gheldof, DamienPublication date:2018Document VersionPublisher's PDF, also known as Version of recordLink to publicationCitation for pulished version (HARVARD):Bouvy, C, Evrard, J, Siriez, R, Mullier, F, Douxfils, J & Gheldof, D 2018, 'Removal of DOACs from plasma:performance comparison and pre-analytical considerations of three different devices', European Congress onThrombosis and Haemostasis, Marseille, France, 24/10/18 - 26/10/18.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. 2020IntroductionMethodsCéline Bouvy1, Jonathan Evrard2, Romain Siriez2, François Mullier3, Jonathan Douxfils1,2, Damien Gheldof21QUALIblood sa, 2Department of Pharmacy, Namur Thrombosis and Hemostasis Center (NTHC), Namur Research Institute for Life Sciences (NARILIS),University of Namur, Namur, Belgium 3Hematology laboratory, Namur Thrombosis and Hemostasis Center (NTHC), Namur Research Institute for Life Sciences(NARILIS), Université Catholique de Louvain, Yvoir, BelgiumGiven the plethora of coagulation tests influenced by Direct Oral Anti-Coagulants (DOACs), it would be of particular interest to remove DOACs from a sample. This couldenable a better investigation of an underlying plasma defect potentially hidden by a DOAC interference. In this context, several DOACs-removal devices have beendeveloped for a potential use in clinical routine. The transfer of plasma through a filter or the addition of an adsorbing agent is currently under investigation.The aim of this study was to evaluate the performances of three devices enabling the removal of DOACs from spiked plasma samples. Their efficiency to eliminateDOACs from plasma, the impact of the transfer through the filters on the coagulation and their ergonomics were investigated.Fresh normal pooled plasma from 6 healthy volunteers were mixed with either dabigatran, rivaroxaban or apixaban at 0-125-250-500 ng/mL theoretical final concentration.Six hundred µL of plasma were tested before and after filtration on DOAC filter (Stago, France), DOAC Stop (Haematex Research, Australia) or on Hemofilter (Hemosafe,Belgium) on a STA-R Max2 analyzer using calibrated STA-Liquid anti-Xa or STA-ECAII for dosage of anti-Xa and anti-IIa drugs, respectively (all products from Stago,France). Prothrombin time (PT) and activated partial thromboplastin time (aPTT) were also analyzed on the STA-R Max2. Several usage data regarding these devices werecollected throughout the study.We thank Stago for having kindly provide us with reagents and DOAC filters for this study. Dr. Céline Bouvy: celine.bouvy@qualiblood.euinfo@qualiblood.euAcknowledgement Contact1- Procedure for DOAC removalDOAC filter DOAC Stop HemofilterCentrifugation 300g, 15 min Gentle mix 5 min Centrifugation200g, 3 min Centrifugation2000g, 2 min Quick vortex and 5 min incubationSupernatanttransferTotal time for use15 min 7 min 8 minPlasma volume loss100±13 µL 150 µL* 68±3 µL*defined in the experimental design.Spiked samples rangeApixaban (ng/mL)STA-Liquid anti-Xa0 100 200 300 400 5000100200300400500no filterDOAC filterDOAC StopHemofilterSpiked samples rangeRivaroxaban (ng/mL)STA-Liquid anti-Xa0 100 200 300 400 5000100200300400500Spiked samples rangeDabigatran (ng/mL)STA-ECAII0 100 200 300 400 50001002003004005002- DOAC removal efficiency3- Impact on PT and aPTTDabigatran Rivaroxaban ApixabanSpiked samples rangePT (sec)0 100 200 300 400 5000102030Spiked samples rangePT (sec)0 100 200 300 400 5000102030 no filterDOAC filterDOAC StopHemofilterSpiked samples rangePT (sec)0 100 200 300 400 5000102030Spiked samples rangeaPTT (sec)0 100 200 300 400 50020406080 no filterDOAC filterDOAC StopHemofilterSpiked samples rangeaPTT (sec)0 100 200 300 400 50020406080Spiked samples rangeaPTT (sec)0 100 200 300 400 50020406080Some discrepancies can be observed between theoretical and actual dosages of dabigatran, rivaroxaban and apixaban inspiked samples. Results also show that all devices enable a sufficient removal of rivaroxaban and dabigatran to lowermeasurements under the limits of detection of the instrument (LOD is presented as horizontal dotted line). For apixaban, onlythe DOAC Stop and the Hemofilter enable this sufficient elimination while residual amounts of apixaban are still measurableafter the use of the DOAC filter on samples containing the highest concentrations tested (250 and 500 ng/mL theoretical).All the DOACs-removal devices were able to restore normal PT and aPTT, but Hemofilter introduced a slight shortening of PTunder every condition while it has no impact on aPTT.Regarding their ergonomics and usage data, the DOACStop procedure is the quickest (7 min). However, thecomplete elimination of the adsorbing agent is difficult andblack residues in the sample were still visible after theprocedure and may lead to inadvertent transfer of theblack residue which will re-introduce the DOAC into thesample. The use of DOAC filter and Hemofilter include lesssteps in their protocol. The Hemofilter induces the lowerloss of sample volume.ConclusionIn conclusion, the DOAC Filter and the Hemofilter are the easiest DOAC removal devices to use. In addition, no visible residues potentially interfering with measurement areobserved with these devices as opposed to DOAC Stop. However, the DOAC Filter is not able to eliminate apixaban at concentration higher than 250 ng/mL.Removal of DOACs from plasma: performance comparison and pre-analytical considerations of three different devices

Removal of DOACs from plasma:performance comparison and pre-analytical considerations of three different devices

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Removal of DOACs from plasma:performance comparison and pre-analytical considerations of three different devices

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