Diagnostic accuracy of thromboelastometry and its correlation with the HPLC-MS/MS quantification test

ABSTRACT

The aim of the study was to evaluate the diagnostic accuracy of thromboelastometry for assessing rivaroxaban concentrations. The accuracy of thromboelastometry was compared with the high-performance liquid chromatography tandem mass spectrometry (HPLC-MS/MS) method, which is the gold standard for drug plasma monitoring (the reference standard). Forty-six clinically stable patients were treated with 10, 15, or 20 mg of rivaroxaban once daily (OD group) or 15 mg twice a day (BID group) (no particular indication for treatment). Patient samples were collected 2 h after the use of the medication (peak) and 2 h before the next dose (trough). The rivaroxaban plasma concentrations were determined via HPLC-MS/MS, and thromboelastometry was performed using a ROTEM® delta analyzer. There were significant prolongations in clotting time (CT) for the 10, 15, and 20 mg of rivaroxaban treatments in the OD groups. In the 15 mg BID group, the responses at the peak and trough times were similar. At the peak times, there was a positive correlation between the plasma concentration of rivaroxaban and CT (Spearman correlation rho=0.788, P<0.001) and clot formation time (rho=0.784, P<0.001), and a negative correlation for alpha angle (rho=−0.771, P<0.001), amplitude after 5 min (rho=−0.763, P<0.001), and amplitude after 10 min (rho=−0.680, P<0.001). The CT presented higher specificity and sensitivity using the cut-off determined by the receiver characteristics curve. ROTEM has potential as screening tool to measure possible bleeding risk associated with rivaroxaban plasma levels.