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

Laure Morimont, Marie Didembourg, Hélène Haguet, Élise Modaffari, Maxence Tillier, Céline Bouvy, Aurélien Lebreton, Jean-Michel Dogné, Jonathan Douxfils

    Research output: Contribution to journalArticlepeer-review

    Abstract

    Background and objective: Although the endogenous thrombin potential (ETP)-based activated protein C (APC) resistance is recommended for the development of steroid contraceptive agents, one of the main limitations of this technique was its lack of standardization, which hampered study-to-study comparison. A validated methodology that meets all the regulatory requirements in terms of analytical performances has been developed recently. To ensure a wide implementation of this test, the assessment of the interlaboratory variability was needed.

    Method: The assay was implemented in three testing laboratories. First, dose-response curves were performed to locally define APC concentration leading to 90% of ETP inhibition on healthy donors. Intra- and inter-run repeatability were assessed on a reference plasma and three quality controls. To investigate the variability in results among the different testing units, 60 donor samples were analyzed at each site.

    Results: The APC concentration leading to 90% of ETP inhibition was defined at 1.21 µg/ml and 1.14 µg/ml in the two receiving units. Intra- and inter-run repeatability showed standard deviation below 3%. Analyses of the 60 donor samples showed no statistically significant difference. The sensitivity of the test in the different laboratories was maintained and subgroup analyses still reported significant differences depending on hormonal status of donors.

    Conclusion: This study is the first reporting the interlaboratory variability of the ETP-based APC resistance assay. Data revealed excellent intra- and interlaboratory reproducibility. These results support the concept that this blood coagulation test provides an appropriate sensitivity irrespective of the laboratory in which analyses are performed.

    Original languageEnglish
    Article numbere12612
    JournalResearch and Practice in Thrombosis and Haemostasis
    Volume5
    Issue number7
    DOIs
    Publication statusPublished - 2 Nov 2021

    Keywords

    • activated protein C resistance
    • blood coagulation test
    • contraceptive agents
    • laboratories
    • reproducibility of results

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