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.

Quantifying Residual Rivaroxaban Plasma Concentration after Antagonization with Andexanet Alfa: A Difficult Task in Routine Clinical Practice

“…In the case presented here, we observed contrasting results of HPLC as well as anti-Xa assay versus ROTEM. Although a positive correlation was demonstrated between plasma concentrations of rivaroxaban measured by HPLC and CT ROTEM, 11 we observed a negative correlation between these parameters in our case. The viscoelastic test revealed a marked improvement of coagulation (EXTEM CT decreased from 149 to 58 seconds, see Table 4 ), which correlates with the improvement of the patient's clinical condition.…”

The impact of direct oral anticoagulants on viscoelastic testing – A systematic review

“…Seventeen studies assessed rivaroxaban measurements in whole blood with ROTEM (Werfen, Bedford, MA, USA) ( 18 , 19 , 23 , 24 , 27 , 28 , 30 , 31 , 34 , 36 , 39 – 41 , 44 , 45 , 47 , 48 ) ( Supplementary Table 2.1 ). A significant correlation between rivaroxaban plasma concentration and duration of clotting time (CT) was shown for EXTEM (strong to very strong correlation) ( 24 , 28 , 30 , 34 , 44 , 45 ), INTEM (moderate to strong correlation) ( 24 , 28 , 30 , 34 , 45 ), NATEM (strong correlation) ( 19 ), FIBTEM (strong correlation) ( 44 ), and HEPTEM (strong correlation) ( 28 ) assays ( Table 1.1 ). One study did not find any significant effect of rivaroxaban on ROTEM parameters ( 31 ).…”

Use of direct oral anticoagulants in ICU patients. Part I – Applied pharmacology

“…studies have shown a linear relationship between clotting time measured by ROteM and increasing plasma concentration of DOAcs including factor Xainhibitors and dabigatran. this offers reliable clinical potential of ROteM to predict the DOAc concentration in cases of severe bleeding [39,40].…”