Commentary: The ETP-based APC resistance assay remains the gold standard for evaluating the APC resistance phenotype in users of combined oral contraceptives

doi:10.3389/fcvm.2025.1611404

Comment

. 2025 Jul 15:12:1611404.

doi: 10.3389/fcvm.2025.1611404. eCollection 2025.

Commentary: The ETP-based APC resistance assay remains the gold standard for evaluating the APC resistance phenotype in users of combined oral contraceptives

Laure Morimont^{1

2}, Jonathan Douxfils^{1

2

3}

Affiliations

¹ Qualiblood sa, QualiResearch, Liège, Belgium.
² Clinical Pharmacology and Toxicology Research Unit, Namur Research Institute for Life Sciences, University of Namur, Namur, Belgium.
³ Hematology Department, Centre Hospitalier Universitaire Clermont-Ferrand, Hopital Estaing, Clermont-Ferrand, France.

PMID: 40734977
PMCID: PMC12305808
DOI: 10.3389/fcvm.2025.1611404

Comment

Commentary: The ETP-based APC resistance assay remains the gold standard for evaluating the APC resistance phenotype in users of combined oral contraceptives

Laure Morimont et al. Front Cardiovasc Med. 2025.

. 2025 Jul 15:12:1611404.

doi: 10.3389/fcvm.2025.1611404. eCollection 2025.

Authors

Laure Morimont^{1

2}, Jonathan Douxfils^{1

2

3}

Affiliations

¹ Qualiblood sa, QualiResearch, Liège, Belgium.
² Clinical Pharmacology and Toxicology Research Unit, Namur Research Institute for Life Sciences, University of Namur, Namur, Belgium.
³ Hematology Department, Centre Hospitalier Universitaire Clermont-Ferrand, Hopital Estaing, Clermont-Ferrand, France.

PMID: 40734977
PMCID: PMC12305808
DOI: 10.3389/fcvm.2025.1611404

No abstract available

Keywords: ETP-based APC resistance assay; activated protein C (APC); activated protein C resistance; combined oral contraceptives (COC); endogenous thrombin potential (ETP); thrombomodulin (TM).

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Conflict of interest statement

Author LM was employed by the company Qualiblood sa. JD is the founder of Qualiblood sa, a company involved in the development and validation of the ETP-based activated protein C resistance assay. JD received consultancy fees from Gedeon Richter, Estetra, and Mithra Pharmaceuticals. The authors declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision.

Comment on

Thrombomodulin is a stronger indicator of combined oral contraceptives-induced activated protein C pathway resistance in the thrombin generation test than activated protein C.
Ninivaggi M, Sokolova L, Donkervoort D, de Laat B, de Laat-Kremers R. Ninivaggi M, et al. Front Cardiovasc Med. 2024 Nov 29;11:1490601. doi: 10.3389/fcvm.2024.1490601. eCollection 2024. Front Cardiovasc Med. 2024. PMID: 39677039 Free PMC article.

References

1. de Bastos M, Stegeman BH, Rosendaal FR, Van Hylckama Vlieg A, Helmerhorst FM, Stijnen T, et al. Combined oral contraceptives: venous thrombosis. Cochrane Database Syst Rev. (2014) 3:CD010813. 10.1002/14651858.CD010813.pub2 - DOI - PMC - PubMed
1. Creinin MD, Jensen JT. Oral contraceptive generations—time to stop using a marketing myth to define nomenclature. Contraception. (2020) 102(3):143–4. 10.1016/j.contraception.2020.05.017 - DOI - PubMed
1. Douxfils J, Raskin L, Didembourg M, Donis N, Dogne J-M, Morimont L, et al. Are natural estrogens used in contraception at lower risk of venous thromboembolism than synthetic ones? A systematic literature review and meta-analysis. Front Endocrinol (Lausanne). (2024) 15:1428597. 10.3389/fendo.2024.1428597 - DOI - PMC - PubMed
1. Morimont L, Haguet H, Dogné J-M, Gaspard U, Douxfils J. Combined oral contraceptives and venous thromboembolism: review and perspective to mitigate the risk. Front Endocrinol (Lausanne). (2021) 12:769187. 10.3389/fendo.2021.769187 - DOI - PMC - PubMed
1. Douxfils J, Morimont L, Delvigne A-S, Devel P, Masereel B, Haguet H, et al. Validation and standardization of the ETP-based activated protein C resistance test for the clinical investigation of steroid contraceptives in women: an unmet clinical and regulatory need. Clin Chem Lab Med. (2020) 58(2):294–305. 10.1515/cclm-2019-0471 - DOI - PubMed

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[1] de Bastos M, Stegeman BH, Rosendaal FR, Van Hylckama Vlieg A, Helmerhorst FM, Stijnen T, et al. Combined oral contraceptives: venous thrombosis. Cochrane Database Syst Rev. (2014) 3:CD010813. 10.1002/14651858.CD010813.pub2 - DOI - PMC - PubMed

[2] de Bastos M, Stegeman BH, Rosendaal FR, Van Hylckama Vlieg A, Helmerhorst FM, Stijnen T, et al. Combined oral contraceptives: venous thrombosis. Cochrane Database Syst Rev. (2014) 3:CD010813. 10.1002/14651858.CD010813.pub2 - DOI - PMC - PubMed

[3] Creinin MD, Jensen JT. Oral contraceptive generations—time to stop using a marketing myth to define nomenclature. Contraception. (2020) 102(3):143–4. 10.1016/j.contraception.2020.05.017 - DOI - PubMed

[4] Creinin MD, Jensen JT. Oral contraceptive generations—time to stop using a marketing myth to define nomenclature. Contraception. (2020) 102(3):143–4. 10.1016/j.contraception.2020.05.017 - DOI - PubMed

[5] Douxfils J, Raskin L, Didembourg M, Donis N, Dogne J-M, Morimont L, et al. Are natural estrogens used in contraception at lower risk of venous thromboembolism than synthetic ones? A systematic literature review and meta-analysis. Front Endocrinol (Lausanne). (2024) 15:1428597. 10.3389/fendo.2024.1428597 - DOI - PMC - PubMed

[6] Douxfils J, Raskin L, Didembourg M, Donis N, Dogne J-M, Morimont L, et al. Are natural estrogens used in contraception at lower risk of venous thromboembolism than synthetic ones? A systematic literature review and meta-analysis. Front Endocrinol (Lausanne). (2024) 15:1428597. 10.3389/fendo.2024.1428597 - DOI - PMC - PubMed

[7] Morimont L, Haguet H, Dogné J-M, Gaspard U, Douxfils J. Combined oral contraceptives and venous thromboembolism: review and perspective to mitigate the risk. Front Endocrinol (Lausanne). (2021) 12:769187. 10.3389/fendo.2021.769187 - DOI - PMC - PubMed

[8] Morimont L, Haguet H, Dogné J-M, Gaspard U, Douxfils J. Combined oral contraceptives and venous thromboembolism: review and perspective to mitigate the risk. Front Endocrinol (Lausanne). (2021) 12:769187. 10.3389/fendo.2021.769187 - DOI - PMC - PubMed

[9] Douxfils J, Morimont L, Delvigne A-S, Devel P, Masereel B, Haguet H, et al. Validation and standardization of the ETP-based activated protein C resistance test for the clinical investigation of steroid contraceptives in women: an unmet clinical and regulatory need. Clin Chem Lab Med. (2020) 58(2):294–305. 10.1515/cclm-2019-0471 - DOI - PubMed

[10] Douxfils J, Morimont L, Delvigne A-S, Devel P, Masereel B, Haguet H, et al. Validation and standardization of the ETP-based activated protein C resistance test for the clinical investigation of steroid contraceptives in women: an unmet clinical and regulatory need. Clin Chem Lab Med. (2020) 58(2):294–305. 10.1515/cclm-2019-0471 - DOI - PubMed

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Commentary: The ETP-based APC resistance assay remains the gold standard for evaluating the APC resistance phenotype in users of combined oral contraceptives

Affiliations

Commentary: The ETP-based APC resistance assay remains the gold standard for evaluating the APC resistance phenotype in users of combined oral contraceptives

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