Assessment of the impact of rivaroxaban on coagulation assays: Laboratory recommendations for the monitoring of rivaroxaban and review of the literature

Introduction: Rivaroxaban does not require monitoring nor frequent dose adjustment. However, searching for the optimal dose in the individual patient may be useful in some situations. Aim: To determine which coagulation assay could be used to assess the impact of rivaroxaban on haemostasis and provide guidelines for the interpretation of routine lab tests. Materials: Rivaroxaban was spiked at concentrations ranging from 11 to 1090 ng/mL in plateletpoor plasma. A large panel of coagulation assays was tested. Results: A concentration dependent prolongation of aPTT, PT, dPT, PiCT was observed. PT and dPT were the most sensitive chronometric assays but results varied depending on the reagent (Triniclot PT Excel S > Recombiplastin 2 G > Neoplastin R > Neoplastin CI + > Triniclot PT Excel > Triniclot PT HTF > Innovin). FXa chromogenic assays showed the highest sensitivity. In TGA, Cmax was the most sensitive parameter with the tissue factor induced pathway. Rivaroxaban interferes on haemostasis diagnostic tests such the measurement of clotting factors, fibrinogen, antithrombin, proteins C and S, activated protein-C resistance and Xa-based chomogenic assays. Conclusions: PT may be used as screening test to assess the risk of bleedings. A more specific and sensitive assay such as Biophen DiXaI using calibrators should be used to confirm the concentration of rivaroxaban. We also propose cut-off associated with a bleeding or thrombosis risk based on pharmacokinetic studies. Standardization of the time between the last intake of rivaroxaban and the sampling is mandatory.