Bouvy, Céline

Devel, Philippe

Dogné, Jean-Michel

Douxfils, Jonathan

Maloteau, Vincent

Morimont, Laure

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.beUniversity of NamurInter-laboratory variability of the standardized ETP-based APC resistance assay(PB0386)Morimont, Laure; Maloteau, Vincent; Devel, Philippe; Dogné, Jean-Michel; Bouvy, Céline;Douxfils, JonathanPublication date:2020Link t  publicationCitation for pulished version (HARVARD):Morimont, L, Maloteau, V, Devel, P, Dogné, J-M, Bouvy, C & Douxfils, J 2020, 'Inter-laboratory variability of thestandardized ETP-based APC resistance assay (PB0386)', ISTH 2020 virtual congress: July 12-14, 2020,12/07/20 - 14/07/20.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: 25. May. 2021Inter-laboratory variability of the standardized ETP-based APC resistance assay (PB0386)INTRODUCTION• Risk minimiza)on measures need to be implemented to reduce thethrombo)c risk associated with the use of combined oralcontracep)ves (COC). However, there is controversy on how toassess the risk at an acceptable cost for the society.• Despite regulatory bodies recommend the assessment of the ETP-based ac)vated protein C (APC) resistance during the developmentof steroid contracep)ves; results are not comparable betweenstudies due to lack of valida)on and standardiza)on.• To overcome this issue, our group recently validated andstandardized this assay.• However, further inves)ga)ons are needed before a wideimplementa)on of this method.CONCLUSIONS• These results demonstrate the transferability of the validated ETP-based APC resistance test between CATs using the same software version.• In order to confirm the reliability of the results obtained with this validated method, its implementation in other centre is essential. • The conduct of a larger multi-centre study should therefore be performed before implementing this technique in the routine setting. RESULTSMETHOD• Analyses were performed on 3 Calibrated AutomatedThrombogram (CAT) with Thrombinoscope soLware (version 5.0 forCAT1&2; version 2.0 for CAT3) and by 3 different operators.• Dose-response curves (n=3) were performed on each device to defined the amount of APC, leading to o (a) 90% of inhibi)on of the ETP on an in-house reference plasma, o (b) the corresponding inhibi)on % on a commercial reference plasma.• Quality controls (n=3) and a subset of real-life samples (n=11) were tested on each equipment. • All measurements were performed in duplicate. ACKNOWLEDGEMENTSThis study was financed by QUALIblood s.aand the brussels-Wallonia federa)on (conven)on no. 8031). AIMTo assess the inter-laboratory variability of the validated ETP-based APC resistance assay.REFERENCES1 Guideline on clinical inves)ga)on of steroid contracep)ves in women -EMEA/CPMP/EWP/519/98 Rev 1.2 Morimont, L., et al. (2020). "Proof of concept of a new scale for the harmoniza)on and the standardiza)on of the ETP-based APC resistance." J Thromb Haemost 18(4): 895-904.3 Douxfils, J., et al. (2020). "Valida)on and standardiza)on of the ETP-based ac)vated protein C resistance test for the clinical inves)ga)on of steroid contracep)ves in women: an unmet clinical and regulatory need." Clin Chem Lab Med 58(2): 294-305.CONTACT INFORMATIONEmail: laure.morimont@qualiblood.euTel: 32 (0)81 72 42 92 L. MORIMONT 1,2, V. Maloteau 2 , P. Devel2, J-M. Dogné2, C. Bouvy1, J. Douxfils1,21 QUALIblood s.a., Namur Belgium2 University of Namur, Department of Pharmacy, Namur Thrombosis and Hemostasis center (NTHC), Namur Research Institute for Life Sciences (NARILIS), Namur, BelgiumIn-house reference plasma Commercial reference plasma[APC]Inhibition %p-valueInhibition %p-valueCAT 1 CAT 2 CAT1 CAT265 mU/mL26,69* 52,05>0.999914,65 27,48>0.999928,71* 56,13 17,18 31,3544,24 59,57 25,53 24,7100 mU/mL64,77 70,39>0.999938,94 40,71>0.999962,63 64,34 37,51 47,369,72 68,21 44,32 45,7130 mU/mL73,9 80,1>0.999946,84 52,14>0.999968,15 76,11 44,37 56,4280,23 77,84 52,77 54,82200 mU/mL90,27 89,45>0.999965,05 67,54>0.999987,92 81,62 68,86 71,8892,09 88,72 71,27 69,99250 mU/mL95,25 93,42>0.999974,02 74,4>0.999991,58 89,48 72,16 78,8395,47 92,47 79,06 74,66300 mU/mL97,19 95,87>0.999978,86 79,58>0.999996,13 82,89* 83,06 85,896,55 95,08 83,69 79,92Defined concentration of APC (95%CI): 217 mU/mL [197 mU/mL-249 mU/mL]Inhibition % Difference CAT 1 CAT 2In-house refplasma  88,66% 94,56% 5,90%Commercial ref plasma64,81% 74,36% 9,55%QC Low 98,19% 100,16% 1,96%QC Norm 31,22% 44,17% 12,95%QC High 7,18% 9,70% 2,52%S1 91,99% 96,34% 4,36%S2 77,01% 81,54% 4,53%S3 78,53% 86,07% 7,54%S4 64,74% 74,16% 9,42%S5 56,94% 64,92% 7,97%S6 68,84% 79,33% 10,49%S7 69,03% 76,53% 7,49%S8 69,02% 76,42% 7,40%S9 46,88% 60,55% 13,67%S10 61,99% 71,36% 9,37%S11 40,69% 50,90% 10,21%Mean deviation 7,83%• A mean devia)on of 7.83% wasobserved when comparing samplestested on both CAT device at thedefined APC concentra)on of 217mU/mL (▶Table 2).• Dose-response curves did not show any significant differences between CAT1 and CAT2 (Dunn’s mul)ple comparison test; p-value > 0.9999) on both, commercial and in-house reference plasma                            ▶Table/Figure 1. • An APC concentra)on of 217 mU/mL led to 90% of inhibi)on of the ETP on the homemadereference plasma and 68% of inhibi)on on the commercial reference plasma▶Table/Figure 1.0 50 100 150 200 250 300020406080100APC (mU/mL)Inhibition %In house reference plasma (R2 0.9997)Commercial reference plasma (R2 0.9933)TABLE 2: Inhibi'on percentageand absolute differencebetween CAT1 and CAT2.FIGURE 1: Total variability between CAT1 and CAT2. The red do>ed line represents thereference range of in-house reference plasma (90±2.5%) and the blue do>ed line representsthe reference range of commercial reference plasma (68±8%). The green do>ed linerepresents the defined concentra'on of APC (217 mU/mL) to fit the reference ranges.TABLE 1: Inhibi'on percentage at 6 concentra'on levels of APC with in-house referenceplasma and commercial reference plasma on CAT1 and CAT2. Inhibi'on % in blue* areoutliers• As the softwareversion of the CAT3was older, somemodifications must beperformed to ensurethe transferability ofthe methodology. Thisis due to importantbackground noisewhich limits theperformance of thisolder version of theCAT3 at low ETP-values.

Inter-laboratory variability of the standardized ETP-based APC resistance assay (PB0386)

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Inter-laboratory variability of the standardized ETP-based APC resistance assay (PB0386)

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