Evaluation of Activated Protein C Resistance Using Thrombin Generation Test

© 2023. The Author(s), under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature..

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.

Medienart:

E-Artikel

Erscheinungsjahr:

2023

Erschienen:

2023

Enthalten in:

Zur Gesamtaufnahme - volume:2663

Enthalten in:

Methods in molecular biology (Clifton, N.J.) - 2663(2023) vom: 19., Seite 211-224

Sprache:

Englisch

Beteiligte Personen:

Douxfils, Jonathan [VerfasserIn]
Bouvy, Céline [VerfasserIn]
Morimont, Laure [VerfasserIn]

Links:

Volltext

Themen:

9001-24-5
Activated protein C resistance
Blood coagulation tests
EC 3.4.21.5
Factor V
Factor V Leiden
Hypercoagulability
Journal Article
Phenotype
Protein C
Thrombin
Thrombin generation
Thrombophilia
Venous thromboembolism

Anmerkungen:

Date Completed 22.05.2023

Date Revised 23.05.2023

published: Print

Citation Status MEDLINE

doi:

10.1007/978-1-0716-3175-1_12

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM357072308