Automated Thrombin Generation Assay for Rivaroxaban, Apixaban, and Edoxaban Measurements.

Meihandoest, Tamana; Studt, Jan-Dirk; Mendez, Adriana; Alberio, Lorenzo; Fontana, Pierre; Wuillemin, Walter A; Schmidt, Adrian; Graf, Lukas; Gerber, Bernhard; Maeder, Gabriela Monika; Bovet, Cédric; Sauter, Thomas C; Nagler, Michael (2021). Automated Thrombin Generation Assay for Rivaroxaban, Apixaban, and Edoxaban Measurements. Frontiers in cardiovascular medicine, 8, p. 717939. 10.3389/fcvm.2021.717939

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Background: The thrombin generation assay (TG) is a promising approach to measure the degree of anticoagulation in patients treated with direct oral anticoagulants (DOAC). A strong association with plasma drug concentrations would be a meaningful argument for the potential use to monitor DOAC. Objectives: We aimed to study the correlation of TG with rivaroxaban, apixaban, and edoxaban drug concentrations in a large, prospective multicenter cross-sectional study. Methods: Five-hundred and fifty-nine patients were included in nine tertiary hospitals. The Technothrombin® TG was conducted in addition to an anti-Xa assay; LC-MS/MS was performed as the reference standard. Results: Correlation (rs) between thrombin generation measurements and drug concentrations was -0.72 for peak thrombin generation (95% confidence interval, CI, -0.77, -0.66), -0.55 for area under the curve (AUC; 95% CI -0.61, -0.48), and 0.80 for lag time (95% CI 0.75, 0.84). In contrast, rs was 0.96 with results of the anti-Xa activity (95% CI 0.95-0.97). Sensitivity with regard to the clinically relevant cut-off value of 50 μgL-1 was 49% in case of peak thrombin generation (95% CI, 44, 55), 29% in case of AUC (95% CI, 24, 34), and 64% in case of lag time (95% CI, 58, 69). Sensitivity of the anti-Xa assay was 95% (95% CI, 92, 97). Conclusions: The correlation of thrombin generation measurements with DOAC drug concentrations was weak, and clinically relevant drug levels were not predicted correctly. Our results do not support an application of TG in the monitoring of DOAC.

Item Type:

Journal Article (Original Article)


04 Faculty of Medicine > Department of Intensive Care, Emergency Medicine and Anaesthesiology (DINA) > University Emergency Center
04 Faculty of Medicine > Department of Haematology, Oncology, Infectious Diseases, Laboratory Medicine and Hospital Pharmacy (DOLS) > Institute of Clinical Chemistry

UniBE Contributor:

Meihandoest, Tamana, Bovet, Cédric, Sauter, Thomas Christian, Nagler, Michael


600 Technology > 610 Medicine & health






Karin Balmer

Date Deposited:

05 Nov 2021 09:52

Last Modified:

05 Dec 2022 15:54

Publisher DOI:


PubMed ID:


Uncontrolled Keywords:

anti-Xa assay apixaban diagnostic accuracy direct oral anticoagulants edoxaban laboratory monitoring rivaroxaban thrombin generation assay




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