Whole blood coagulation assays ROTEM and T-TAS to monitor dabigatran treatment

Abstract Background A rapid and reliable assessment of the dabigatran effect is desirable in dabigatran treated patients with uncontrolled bleeding or before acute surgery. Objective To evaluate how the viscoelastic point-of-care test Rotational thromboelastometry (ROTEM) and Total Thrombus-formation system (T-TAS), which studies thrombus formation under flowing conditions, correlate with dabigatran concentrations in patients with atrial fibrillation (AF). Method ROTEM using the reagents In-tem, Ex-tem, Fib-tem or low tissue factor concentration (TF), and T-TAS with the AR-chip (shear rate 600 s − 1 , representing flow in large arteries) were investigated in whole blood samples. Plasma concentrations were determined by mass spectrometry (LC-MS/MS) at trough and post-dose in 30 patients on dabigatran 150 mg BID. Results Median plasma dabigatran concentrations at trough were 86 ng/mL (29–150) and post-dose (2.8 h after ingestion) 175 ng/mL (67–490). The ROTEM clotting time (CT) correlated strongly with dabigatran concentrations when activated with the reagents Ex-tem ( r = 0.92, p < 0.01) and Fib-tem ( r = 0.93, p < 0.01), while with In-tem and low TF the correlation was weaker ( r = 0.72 and r = 0.36, p < 0.01). There were significant but weaker correlations also between dabigatran concentrations and T-TAS variables ( r -values 0.39–0.41, p < 0.01), aPTT ( r = 0.70, p < 0.01) and PT-INR ( r = 0.43, p < 0.01) respectively. Conclusions ROTEM Ex-tem and Fib-tem CT shows a strong correlation with dabigatran concentrations in real-life AF-patients, and results are obtained within minutes. This could make ROTEM useful in acute situations. T-TAS detect differences in hemostasis caused by dabigatran, but the relationships to plasma concentrations of dabigatran are weaker than for ROTEM CT with the settings used in this study.