Correlation of Thromboelastography with Apparent Rivaroxaban Concentration

Abstract

Editor’s Perspective What We Already Know about This Topic What This Article Tells Us That Is New Background Concern remains over reliable point-of-care testing to guide reversal of rivaroxaban, a commonly used factor Xa inhibitor, in high-acuity settings. Thromboelastography (TEG), a point-of-care viscoelastic assay, may have the ability to detect the anticoagulant effect of rivaroxaban. The authors ascertained the association of apparent rivaroxaban concentration with thromboelastography reaction time, i.e., time elapsed from blood sample placement in analyzer until beginning of clot formation, as measured using TEG and TEG6S instruments (Haemonetics Corporation, USA), hypothesizing that reaction time would correlate to degree of functional factor Xa impairment. Methods The authors prospectively performed a diagnostic accuracy study comparing coagulation assays to apparent (i.e., indirectly assessed) rivaroxaban concentration in trauma patients with and without preinjury rivaroxaban presenting to a single center between April 2016 and July 2018. Blood samples at admission and after reversal or 24 h postadmission underwent TEG, TEG6S, thrombin generation assay, anti–factor Xa chromogenic assay, prothrombin time (PT), and ecarin chromogenic assay testing. The authors determined correlation of kaolin TEG, TEG6S, and prothrombin time to apparent rivaroxaban concentration. Receiver operating characteristic curve compared capacity to distinguish therapeutic rivaroxaban concentration (i.e., greater than or equal to 50 ng/ml) from nontherapeutic concentrations. Results Eighty rivaroxaban patients were compared to 20 controls. Significant strong correlations existed between rivaroxaban concentration and TEG reaction time (ρ = 0.67; P < 0.001), TEG6S reaction time (ρ = 0.68; P < 0.001), and prothrombin time (ρ = 0.73; P < 0.001), however reaction time remained within the defined normal range for the assay. Rivaroxaban concentration demonstrated strong but not significant association with coagulation assays postreversal (n = 9; TEG reaction time ρ = 0.62; P = 0.101; TEG6S reaction time ρ = 0.57; P = 0.112) and small nonsignificant association for controls (TEG reaction time: ρ = −0.04; P = 0.845; TEG6S reaction time: ρ = −0.09; P = 0.667; PT-neoplastine: ρ = 0.19; P = 0.301). Rivaroxaban concentration (area under the curve, 0.91) and TEG6S reaction time (area under the curve, 0.84) best predicted therapeutic rivaroxaban concentration and exhibited similar receiver operating characteristic curves (P = 0.180). Conclusions Although TEG6S demonstrates significant strong correlation with rivaroxaban concentration, values within normal range limit clinical utility rendering rivaroxaban concentration the gold standard in measuring anticoagulant effect.

Anticoagulation Monitoring for Perioperative Physicians

“…More recently, commercially produced reagents for the ROTEM and TEG® 6S platforms have been utilized to provide qualitative assessment of direct oral anticoagulant effects. 62,63 Similarly, the ecarin clotting assay and the Russel viper venom test have been used on the ClotPro platform to assess plasma concentrations of dabigatran and factor Xa inhibitors, respectively. 64,65 These may eventually allow perioperative physicians to follow reversal of oral DTIs and factor Xa inhibitors, as doing so with currently available testing options is not recommended.…”

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

“…Thirteen studies described rivaroxaban action in whole blood with TEG (Haemonetics Corporation, Boston MA, U.S.A.) ( 20 – 22 , 25 , 26 , 31 – 33 , 35 , 37 , 42 , 43 , 46 ) ( Supplementary Table 2.2 ). Of these, four studies did not report the exact rivaroxaban concentration under which conditions the viscoelastic tests were performed ( 22 , 25 , 32 , 33 ).…”

“…A significant correlation between rivaroxaban plasma concentration and reaction time (R) have been reported for the specific anti-factor-Xa channel [AFXa] (strong to very strong correlation) ( 20 , 21 , 37 ), and for citrated kaolin channel (moderate to strong correlation) ( 35 , 37 ).…”

Coagulation Management after Trauma in the Presence of Direct Oral Anticoagulants

“…In ROTEM, we expect a prolonged clotting time in the extrinsically activated thromboelastometry (EXTEM) assay that is related to the Xa inhibitor's plasma concentration, 9 and in thrombelastography a prolonged reaction time. 10 Although typical major trauma patients were absent in the mentioned andexanet alfa studies, [4][5][6] reversal of anticoagulation may be indicated in such patients. It is unlikely that one single drug will ever be the "magic bullet" of coagulation management.…”