Interlaboratory variability of activated protein C resistance using the ETP‐based APC resistance assay

Morimont, Laure; Didembourg, Marie; Haguet, Hélène; Modaffari, Elise; Tillier, Maxence; Bouvy, Céline; Lebreton, Aurélien; Dogné, Jean‐Michel; Douxfils, Jonathan

doi:10.1002/rth2.12612

Cited by 6 publications

(3 citation statements)

References 16 publications

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“…64 This enabled the reduction of inter-laboratory variability and allowed laboratory-to-laboratory and study-to-study comparison and evaluation. 75 Ultimately, this validation provides Fig. 3 Thrombin generation curves in absence (continuous lines) and in presence of APC (dotted lines) of healthy donors (blue), of a woman carrier of a heterozygous FV Leiden (green) and of women using combined oral contraceptives containing either ethinylestradiol (EE) with levonorgestrel (yellow), with desogestrel (orange) or with drospirenone (red).…”

Section: Laboratory Testing For Apc Resistance Clotting Time-based Assaymentioning

confidence: 99%

“…64 This enabled the reduction of inter-laboratory variability and allowed laboratory-to-laboratory and study-to-study comparison and evaluation. 75 Ultimately, this validation provides pharmaceutical industries, regulatory bodies, and physicians with a reproducible sensitive and validated assay that could be proposed as a gold standard for the assessment of all types of APCR.…”

Section: Laboratory Testing For Apc Resistancementioning

confidence: 99%

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Laboratory Testing for the Evaluation of Phenotypic Activated Protein C Resistance

Morimont

Donis²,

Bouvy³

et al. 2022

Semin Thromb Hemost

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Activated protein C (APC) resistance (APCR) is considered a risk factor of venous thromboembolism (VTE). The most common genetic disorder conferring APCR is a factor (F) V Leiden mutation, but many other factors are also implicated, such as other F5 mutations (e.g., FV Hong-Kong and FV Cambridge), protein S deficiency, elevated factor VIII, exogenous hormone use, pregnancy and postpartum, depending on how APCR is defined. Considering the large population affected, the detection of this phenotype is crucial. Two types of tests are currently available: clotting time-based assays (with several versions) and thrombin generation-based assays with the endogenous thrombin potential (ETP)-based assay. The purpose of this review is therefore to discuss the performances of these tests and the cases in which it would be appropriate to use one over the other. Initially, as APCR was thought to be solely related to the FV Leiden mutation, the objective was to obtain a 100% specific assay. Clotting-time based assays were thus specifically designed to detect this inherited condition. Later on, an APCR condition without a FV Leiden mutation was identified and highlighted as an independent risk factor of VTE. Therefore, the development of a less specific assay was needed and a global coagulation test was proposed, known as the ETP-based APCR assay. In light of the above, these tests should not be used for the same purpose. Clotting time-based assays should only be recommended as a screening test for the detection of FV mutations prior to confirmation by genetic testing. On the other hand, the ETP-based APC resistance assay, in addition to being able to detect any type of APCR, could be proposed as a global screening test as it assesses the entire coagulation process.

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Section: Laboratory Testing For Apc Resistance Clotting Time-based Assaymentioning

confidence: 99%

“…64 This enabled the reduction of inter-laboratory variability and allowed laboratory-to-laboratory and study-to-study comparison and evaluation. 75 Ultimately, this validation provides pharmaceutical industries, regulatory bodies, and physicians with a reproducible sensitive and validated assay that could be proposed as a gold standard for the assessment of all types of APCR.…”

Section: Laboratory Testing For Apc Resistancementioning

confidence: 99%

Laboratory Testing for the Evaluation of Phenotypic Activated Protein C Resistance

Morimont

Donis²,

Bouvy³

et al. 2022

Semin Thromb Hemost

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“…The ETP‐based APC resistance assay was validated on the calibrated automated thrombogram (CAT) device using commercially available reagents to ensure batch‐to‐batch traceability, recovery, and reproducibility of the method over time 11 . Recently, the interlaboratory variability study supported the concept that the ETP‐based APC resistance, performed with a validated and standardized methodology, provides an adequate sensitivity and an excellent interlaboratory reproducibility 15 . Nevertheless, the CAT mostly remains a research platform, and the implementation of the ETP‐based APC resistance on an automated analyzer is of paramount importance to have this innovative biomarker available for the clinicians in their daily practice.…”

Section: Introductionmentioning

confidence: 99%

Analytical performance of the endogenous thrombin potential–based activated protein C resistance assay on the automated ST Genesia system

Morimont

Leclercq

Didembourg

et al. 2022

Research and Practice in Thrombosis and Haemostasis

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Background The evaluation of activated protein C (APC) resistance based on the endogenous thrombin potential (ETP) is recommended during the development of steroid contraceptives in women. In 2019, this assay was validated on the calibrated automated thrombogram (CAT) device. However, in view of its screening potential, its automation is essential. Objectives To transfer the ETP‐based APC resistance assay on the ST Genesia system using reagent STG‐ThromboScreen with exogenous APC added. Method Dose‐response curves were performed to define APC concentration leading to 90% ETP inhibition on healthy donors. Intra‐ and interrun reproducibility was assessed. The normal range was defined on the basis of 56 samples from healthy individuals. The sensitivity was assessed on 40 samples from women using combined oral contraceptives (COCs). A method comparison with the validated ETP‐based APC resistance on the CAT system was performed. Results were expressed in normalized APC sensitivity ratio (nAPCsr). Results The APC concentration leading to 90% ETP inhibition was 652 mU/mL. Intra‐ and interrun reproducibility showed standard deviation <4%. The nAPCsr normal range stood between 0.00 and 2.20. Analyses of 40 samples from women using COCs confirmed the good sensitivity of the assay. Compared to the CAT system, nAPCsr values were slightly higher on the automated system. Conclusion This study is the first reporting the analytical performances of the ETP‐based APC resistance assay on an automated platform. Results support the concept that this test, when incorporated into clinical routine, could become a promising regulatory and clinical tool to document on the thrombogenicity of female hormonal therapies.

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Evaluation of Activated Protein C Resistance Using Thrombin Generation Test

Douxfils

Bouvy²,

Morimont

2023

Methods in Molecular Biology

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Interlaboratory variability of activated protein C resistance using the ETP‐based APC resistance assay

Cited by 6 publications

References 16 publications

Laboratory Testing for the Evaluation of Phenotypic Activated Protein C Resistance

Laboratory Testing for the Evaluation of Phenotypic Activated Protein C Resistance

Analytical performance of the endogenous thrombin potential–based activated protein C resistance assay on the automated ST Genesia system

Evaluation of Activated Protein C Resistance Using Thrombin Generation Test

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