The effect of dabigatran on thrombin generation and coagulation assays in rabbit and human plasma.

OBJECTIVES: Dabigatran etexilate is widely used for stroke prevention in the patients with atrial fibrillation. The anticoagulation activity of dabigatran is not necessary monitored in routine clinical practice. We aimed to study the effect of dabigatran on thrombin generation (TG) and coagulation assays in rabbit and human plasma.

METHODS: Rabbits received different concentrations of dabigatran etexilate (5 mg/kg, 10 mg/kg). Patients with atrial fibrillation took 110 mg dabigatran etexilate twice daily. The concentrations of dabigatran in rabbit and human plasma were detected by liquid chromatography/tandem mass spectrometry (LC-MS/MS) and ecarin chromogenic assay (ECA). The relationship between plasma dabigatran concentrations and the activated partial thromboplastin time (aPTT), prothrombin time (PT), thrombin time (TT), and TG were evaluated.

RESULTS: There was strong correlation between LC-MS/MS and ECA (P < 0.001). Bland Altman analysis demonstrated that ECA assay could accurately predict human plasma dabigatran concentrations whereas underestimate the plasma concentrations of dabigatran in rabbits. Both the PT and the aPTT assays showed low correlations with dabigatran. The TT assay was highly sensitive to dabigatran levels. Low concentrations of dabigatran paradoxically increased TG.

CONCLUSIONS: LC-MS/MS is the gold standard for detecting the concentrations of dabigatran. ECA correlates well with LC-MS/MS. The coagulation assays depend more on other factors. Paradoxical enhancement of TG may predict clinically rebound hypercoagulability and warrants further exploration.