title: Assessment of the impact of rivaroxaban on coagulation assays: laboratory recommendations for the monitoring of rivaroxaban and review of the literature.
abstract: BACKGROUND
  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.
  
  
  OBJECTIVE
  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.
  
  
  METHODS
  Rivaroxaban was spiked at concentrations ranging from 11 to 1,090 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 2G>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.
authors.affiliation: Department of Pharmacy, Namur Thrombosis and Hemostasis Center (NTHC), Namur Research Institute for LIfe Sciences (NARILIS), University of Namur, B-5000, Belgium. jonathan.douxfils@fundp.ac.be
authors.forename: Jonathan
authors.initials: J
authors.lastname: Douxfils
authors.forename: François
authors.initials: F
authors.lastname: Mullier
authors.forename: Claire
authors.initials: C
authors.lastname: Loosen
authors.forename: Christian
authors.initials: C
authors.lastname: Chatelain
authors.forename: Bernard
authors.initials: B
authors.lastname: Chatelain
authors.forename: Jean-Michel
authors.initials: JM
authors.lastname: Dogné
mesh_terms: D000925:Anticoagulants / Q000008:administration & dosage*; D001777:Blood Coagulation / Q000187:drug effects*; D001780:Blood Coagulation Tests / Q000379:methods*; D006801:Humans; D009025:Morpholines / Q000008:administration & dosage*; D011517:Prothrombin Time; D000069552:Rivaroxaban; D013876:Thiophenes / Q000008:administration & dosage*
chemical_list: D000925:Anticoagulants; D009025:Morpholines; D013876:Thiophenes; D000069552:Rivaroxaban