Rapid determination of anticoagulating effects of dabigatran in whole blood with rotational thromboelastometry and a thrombin‐based trigger

• Published in: Journal of thrombosis and haemostasis Vol. 16; no. 12; pp. 2462 - 2470
• Main Authors: Taune, V., Skeppholm, M., Ågren, A., Gryfelt, G., Malmström, R. E., Wikman, A., Van Ryn, J., Wallén, H.
• Format: Journal Article
• Language: English
• Published: England Elsevier Limited 01.12.2018
• Subjects: Anticoagulants; atrial fibrillation; Clotting; dabigatran; drug monitoring; Medicin och hälsovetenskap; Patients; point‐of‐care test; Thrombin; thromboelastometry; Tissue factor; Viscoelasticity; dabigatran; atrial fibrillation; thromboelastometry; point-of-care test; drug monitoring
• ISSN: 1538-7933; 1538-7836; 1538-7836
• DOI: 10.1111/jth.14308

Essentials A rapid test to detect thrombin inhibition by dabigatran would be valuable in acute situations. A thrombin‐based trigger was applied in whole blood using rotation thromboelastometry. Effects of dabigatran were assessed in vitro and in samples from patients on dabigatran. The test produced data rapidly and was sensitive to dabigatran concentrations from 20 to 500 ng mL−1. Summary Background Rapid determination of the anticoagulant effect of dabigatran is essential in emergency situations. Objective To study a viscoelastic test (rotational thromboelastometry [ROTEM]) for rapid determination of dabigatran effects in whole blood samples. Method ROTEM measurements were performed with comparison of two triggers (thrombin‐based versus the commercial tissue factor‐based trigger Ex‐tem) in samples from 10 healthy donors spiked with dabigatran (20–500 ng mL−1) and in samples from 35 patients receiving dabigatran treatment; 10 healthy subjects served as controls. Clotting time (CT) and the difference in CT without versus with addition of the dabigatran antidote idarucizumab (CTdiff) were measured. Addition of idarucizumab reveals the contribution of dabigatran to ROTEM measurements and its potential reversibility. Results In vitro studies showed that thrombin CT and thrombin CTdiff were more sensitive than Ex‐tem CT and Ex‐tem CTdiff in detecting dabigatran in whole blood samples. In patient samples, when thrombin CT and thrombin CTdiff were used, it was possible to detect dabigatran with a cut‐off of dabigatran at 20 ng mL−1, whereas, when Ex‐tem CT and Ex‐tem CTdiff were used, the method was less sensitive. Data from patient samples were obtained within 15 min of blood sampling. Conclusions ROTEM CT with a thrombin‐based trigger is more sensitive to dabigatran effects than Ex‐tem CT, and detects anticoagulant effects of drug concentrations in the low–very low therapeutic range. Analysis with idarucizumab (CTdiff) reveals dabigatran‐specific effects. As data are rapidly obtained, this method could, with further development and validation of its performance, be suitable for detecting clinically significant dabigatran effects in emergency situations.