The anticoagulant effect of therapeutic levels of dabigatran in atrial fibrillation evaluated by thrombelastography (TEG^®), Hemoclot Thrombin Inhibitor (HTI) assay and Ecarin Clotting Time (ECT)

Abstract

Monitoring the effect of dabigatran (Pradaxa^®) is challenging. The aim of this study was to evaluate if thrombelastography reaction time (TEG^® R) could detect the anticoagulant effect of dabigatran showing a correlation between TEG^® R, Hemoclot Thrombin Inhibitor (HTI) assay and Ecarin Clotting Time (ECT) in patients with non-valvular atrial fibrillation (NVAF). Blood samples from 35 AF patients receiving either 110 mg (n 19) or 150 mg (n 16) dabigatran twice daily were analyzed with TEG^®, HTI and ECT 2–3 h after dabigatran intake. All patients had prolonged TEG^® R. The patients receiving dabigatran 110 mg ×2 had a TEG^® R mean 14.2 min (range 9.1–25), a mean dabigatran concentration measured by HTI of 268.5 ng/mL (range 54–837 ng/mL) and by ECT of 355.7 ng/mL (range 40–1020 ng/mL). The corresponding numbers for patients receiving dabigatran 150 mg ×2 were TEG^® R mean of 12.5 min (range 9.2–23.2 min), mean dabigatran concentration of 179.2 ng/mL by HTI (range 26–687 ng/mL) and by ECT 225.1 ng/mL (range 42–1020 ng/mL). The two dosage groups had comparable anticoagulation demonstrated by equally prolonged TEG^® R (p = .909), HTI (p = .707) and ECT (p = .567). No difference in creatinine levels in the two dosage groups was observed (p = .204) though patients with dabigatran concentration >400 ng/mL had significantly higher creatinine levels (p = .001). Large individual variation of the anticoagulant response was observed. Some patients had TEG^® R values up to three times upper normal limit with immediate risk of bleeding. Our data indicate that TEG^® R reflected dabigatran levels in NVAF patients and that TEG^® R correlated to HTI and ECT.

Keywords:

• Dabigatran
• atrial fibrillation
• thrombelastography
• Hemoclot Thrombin Inhibitor
• anticoagulation

Acknowledgements

Helena Stjernkvist and Karen Dyeremose are thanked for their valuable help in the laboratory.

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

The study was supported by grants from Aase and Ejner Danielsens Foundation, The Hartmann Brothers Foundation, Grosserer L. F. Foghts Foundation, The Research Committee of Rigshospitalet, Familien Hede Nielsens Foundation and the Bønnelycke Foundation.