Comparison of Methods to Determine Rivaroxaban anti-factor Xa activity

Abstract

Background and ObjectivesRivaroxaban, a new oral anti-Xa agent, has been approved for use without routine monitoring, but the lack of a predictable drug level measurement may hinder the management of anticoagulated patients. The aims of the project were to correlate a Anti-Factor Xa assay using commercial calibrators and controls (Riva Activity) with serum drug levels analyzed by HPLC-MS/MS (Riva MS) in patients currently receiving rivaroxaban, and secondly, to correlate the PT/PTT, thrombin generation (CAT assay) and Thromboelastograph (TEG) with the Riva activity and Riva MS. MethodsRecruited patients receiving rivaroxaban prospectively had a total of 3 blood samples taken at least 2hours apart. Plasma was divided for measurement of PT/PTT, Riva activity, rivaroxaban HPCL-MS/MS, and thrombin generation. TEG activity was measured at one random time point for each patient. Correlation and linear regression evaluations were used to compare the different assays. ResultsThe cases were 22 patients on rivaroxaban, age 56+12.6, and 10 healthy controls. There was a strong correlation between Riva activity compared to serum Riva MS (r=0.99). We found a statistically significant correlation between PT/INR compared to serum measurements of Riva MS (r=0.68) and anti-Xa activity (r=0.69). The peak (r=-0.50) and lag time (r=0.57) CAT correlated with Riva MS measurements. There was no correlation between Riva MS and PTT, TEG R, TEG MA, Endogenous Thrombin potential. ConclusionRiva anti-factor Xa activity assay measured with commercial calibrators and controls provides a reliable assessment of rivaroxaban serum levels for patients requiring measurement of anticoagulant activity. Correlation with other coagulation tests is not sufficiently strong to be used clinically.