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.