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Evaluation of Activated Protein C Resistance Using Thrombin Generation Test

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Hemostasis and Thrombosis

Part of the book series: Methods in Molecular Biology ((MIMB,volume 2663))

Abstract

Activated protein C (APC) resistance (APCR) has been identified as a risk factor of venous thromboembolism (VTE). A mutation at the level of factor (F) V has at first permitted the description of this phenotypic pattern and corresponded to a transition (guanine to adenine) at nucleotide 1691 in the gene coding for factor V, resulting in the replacement of arginine at position 506 by a glutamine. This confers to this mutated FV a resistance toward the proteolytic action of the complex formed by activated protein C with protein S. However, many other factors also lead to APCR, 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. All these conditions lead to the phenotypic expression of APCR and are associated with an increased risk of VTE. Considering the large population affected, the proper detection of this phenotype is a public health challenge. Currently, two types of tests are available: clotting time-based assays and their multiple variants and a thrombin generation-based assays and the endogenous thrombin potential (ETP)-based APCR assay. As APCR was thought to be uniquely related to the FV Leiden mutation, clotting time-based assays were specifically designed to detect this inherited condition. Nevertheless, other APCR conditions have been reported but were not captured by these clotting methods. Thus, the ETP-based APCR assay has been proposed as a global coagulation test able to these multiple APCR conditions, as it provides much more information, which makes it a potential candidate for screening coagulopathic conditions before therapeutic interventions. This chapter will describe the current method used for the realization of the ETP-based APC resistance assay.

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Abbreviations

CI:

Confidence interval

COC:

Combined oral contraceptive

CPA:

Cyproterone acetate

DRSP:

Drospirenone

DSG:

Desogestrel

EE:

Ethinylestradiol

GSD:

Gestodene

LNG:

Levonorgestrel

nAPCsr:

Normalized activated protein C sensitivity ratio

RR:

Relative risk

SD:

Standard deviation

VTE:

Venous thromboembolism

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Acknowledgments

The authors would like to thank the technical teams of QUALIblood s.a. and the Walloon region in Belgium.

Disclosure Summary

L.M and C.B. are employees of QUALIblood s.a.; J.D. is the CEO and founder of QUALIblood s.a. and reports personal fees and honorarium from Daiichi Sankyo, Diagnostica Stago, DOASense, Gedeon Richter, Mithra Pharmaceuticals, Norgine, Portola, Roche, and Roche Diagnostics.

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The authors have received permission to reuse some part of the manuscript entitled “Laboratory Testing for the Evaluation of Phenotypic Activated Protein C Resistance” published in Seminars in Thrombosis and Hemostasis (doi: 10.1055/s-0042-1753511; License number: 5420660873500; Licensed Content Publisher: Georg Thieme Verlag KG).

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Authors and Affiliations

  1. Department of Pharmacy, University of Namur, Faculty of Medicine, Namur Research Institute for Life Sciences (NARILIS), Clinical Pharmacology Research Group, Namur, Belgium

    Jonathan Douxfils & Laure Morimont

  2. Department of Research and Development, QUALIblood s.a., Namur, Belgium

    Jonathan Douxfils, Céline Bouvy & Laure Morimont

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  1. Jonathan Douxfils
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Correspondence to Jonathan Douxfils .

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Editors and Affiliations

  1. School of Medical Sciences, Faculty of Medicine and Health University of Sydney, Westmead Hospital, Westmead, NSW, Australia

    Emmanuel J. Favaloro

  2. Hemostasis & Thrombosis Center, University of California, Davis, Sacramento, CA, USA

    Robert C. Gosselin

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Douxfils, J., Bouvy, C., Morimont, L. (2023). Evaluation of Activated Protein C Resistance Using Thrombin Generation Test. In: Favaloro, E.J., Gosselin, R.C. (eds) Hemostasis and Thrombosis. Methods in Molecular Biology, vol 2663. Humana, New York, NY. https://doi.org/10.1007/978-1-0716-3175-1_12

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