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The Effect of trough Dabigatran Plasma Concentration on Thrombin Generation

M. Milic1,2, J. Stanfel1, K. Paradinovic1, V. Seric1

1University Hospital Centre Osijek, Department of Clinical Laboratory Diagnostics, Osijek, Croatia, 2Josip Juraj Strossmayer University of Osijek, Faculty of Mediccine, Osijek, Croatia

Abstract Number: PB0587

Meeting: ISTH 2020 Congress

Theme: Diagnostics and OMICs » Laboratory Diagnostics

Background: The goal of anticoagulation therapy is to reduce generation of thrombin and to prevent thromboembolic event. Thus, an assay that measures plasma potential to produce thrombin may be used for estimation of anticoagulant effect of dabigatran. Thrombin generation assay (TGA) is a global hemostasis assay. It evaluates generation of thrombin in plasma resulting from the action of procoagulant and anticoagulant factors.

Aims: Our aim was to assess the effect of trough dabigatran ex vivo plasma concentration on thrombin generation.

Methods: In 12 patients taking 150mg bd dabigatran for thromboprophylaxis at steady state, we measured trough dabigatran concentration in plasma. Informed consent was obtained and the medical ethics committee approved the study. Blood was collected into 3.2% buffered Na-citrate tubes, (BD Vacutainer). Plasma was stored at -20C for maximum three weeks until analysis. Dabigatran levels were measured on Diagnostica Stago analyzer (STA-R Evolution) using Stago STA-ECA II assay. Endogen thrombin potential (ETP AUC), peak thrombin generation (Cmax), time to peak (tmax) and lag time (tlag) were measured on Siemens analyzer (BCSXP) using Siemens Innovance ETP reagent.

Results: Mean dabigatran concentration (ECA) was 65.3 ng/ml ± 37.9 SD. Spearman´s coefficient of rank correlation (rho) was not statistically significant between dabigatran concentration and ETP AUC (rho=-0.287, p=0.3416), Cmax (rho=-0,245, p=0.4169) and tmax (rho=0.559, p=0.0635). There is a very strong, positive correlation between dabigatran concentration and tlag (rho=0.867, p=0.0040). Regression equation for ECA and tlag is y=0.1486x + 21.6082.

Conclusions: Estimation of dabigatran concentration in plasma could be made by measuring tlag in TGA. Beyond estimation of dabigatran concentration, TGA as a global hemostasis assay, may have additional clinical value in evaluating thrombotic or bleeding risk in patient receiving dabigatran. Therefore, TGA as well as dabigatran concentration should be evaluated in a large clinical trial to correlate them with clinical event.

To cite this abstract in AMA style:

Milic M, Stanfel J, Paradinovic K, Seric V. The Effect of trough Dabigatran Plasma Concentration on Thrombin Generation [abstract]. Res Pract Thromb Haemost. 2020; 4 (Suppl 1). https://abstracts.isth.org/abstract/the-effect-of-trough-dabigatran-plasma-concentration-on-thrombin-generation/. Accessed October 2, 2023.

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