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

Frontiers in Cardiovascular Medicine

Bernhard Gerber²  Thomas C. Sauter³  Michael Nagler⁴  Lukas Graf⁵  Adrian Schmidt⁶  Cédric Bovet⁷  Gabriela Monika Maeder⁷  Tamana Meihandoest⁷  Adriana Mendez⁹  Pierre Fontana^1,10  Walter A. Wuillemin^1,11  Jan-Dirk Studt^1,12  Lorenzo Alberio^1,13 

[1] 0Clinic of Hematology, Oncology Institute of Southern Switzerland, Bellinzona, Switzerland;1University of Zurich, Zurich, Switzerland;2Department of Emergency Medicine, Inselspital, Bern University Hospital, Bern, Switzerland;3Department of Hematology, Inselspital, Bern University Hospital, Bern, Switzerland;Centre for Laboratory Medicine St. Gallen, St. Gallen, Switzerland;Clinic of Medical Oncology and Hematology and Institute of Laboratory Medicine, City Hospital Waid and Triemli, Zurich, Switzerland;Department of Clinical Chemistry, Inselspital, Bern University Hospital, and University of Bern, Bern, Switzerland;Department of Epidemiology, Maastricht University, Maastricht, Netherlands;Department of Laboratory Medicine, Cantonal Hospital Aarau, Aarau, Switzerland;Division of Angiology and Hemostasis, Geneva University Hospital, Geneva, Switzerland;Division of Hematology and Central Hematology Laboratory, Cantonal Hospital of Lucerne and University of Bern, Bern, Switzerland;Division of Medical Oncology and Hematology, University and University Hospital Zurich, Zurich, Switzerland;Service and Central Laboratory of Hematology, CHUV, Lausanne University Hospital, Lausanne, Switzerland;

关键词: diagnostic accuracy;    thrombin generation assay;    anti-Xa assay;    laboratory monitoring;    rivaroxaban;    apixaban;   

DOI  :  10.3389/fcvm.2021.717939

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown