Real-time detection and differentiation of direct oral anticoagulants (rivaroxaban and dabigatran) using modified thromboelastometric reagents.

Timely measurement of direct oral anticoagulants (DOACs) is challenging, though clinically important. We tested the hypotheses, that thromboelastometry is able to detect dabigatran and rivaroxaban and discriminates between dabigatran and rivaroxaban as representatives of the two groups of DOACs. We conducted a prospective-observational study: In-vitro dose-effect-curves for rivaroxaban and dabigatran were performed (n = 10). Ex-vivo: Patients with indication of DOAC treatment (stroke; dabigatran/rivaroxaban) were included (n = 21). Blood samples were analyzed before first intake, at first estimated peak level and at 24 h after first but before following intake and 3 h after 24 h-intake. Standard and modified thromboelastometric-assays, using low tissue factor concentrations (TFTEM) or ecarin (ECATEM) were used. Receiver-operating-characteristics-curve-analysis (ROC), regression-analysis and two-way-ANOVA were performed. In-vitro: TFTEM detected dabigatran and rivaroxaban (ROC_AUC: 0.99; sensitivity/specificity: 100%/98%) but could not discriminate. Dabigatran prolongs CT The thromboelastometric tests TFTEM and ECATEM detect and differentiate rivaroxaban and dabigatran. Further investigations evaluate the other DOACs and the differentiation to phenprocoumon. However, results need to be confirmed in a larger study, and especially cut off values for differentiation need to be calculated from a larger sample size.

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Déclaration de conflit d'intérêts

Declaration of competing interest The study was funded by a research grant from WIFOMED (Verein für Förderung von Wissenschaft und Forschung an der medizinischen Fakultät der Ludwig- Maximilians-Universität München) to Dr. Schäfer. Thromboelastometric machines and reagents were provided by TEM Innovations (Munich, Germany). The funding sponsors WIFOMED (Verein für Förderung von Wissenschaft und Forschung an der medizinischen Fakultät der Ludwig-Maximilians-Universität München) and (TEM Innovations) had no role in the collection, analysis or interpretation of data; in the writing of the manuscript, or in the decision to publish the results. S.T.S. received lecture fees by CSL Behring and research grants by Octapharma. P.G. received lecture fees by CSL Behring, T.W., T.K., V.B., K.F., L.K. and L.C.H. declare no conflict of interest. K.G. serves as medical director at TEM Innovations since 2012.