title: Measuring Rivaroxaban in a clinical laboratory setting, using common coagulation assays, Xa inhibition and thrombin generation.
abstract: BACKGROUND
  Rivaroxaban, a direct Xa inhibitor, is one of the new oral antithrombotic agents for which laboratory monitoring is thought to be unnecessary in most cases due to predictable pharmacokinetics. Circumstances are conceivable, however, in which reliable laboratory testing of Rivaroxaban is desirable. The aim of the present in vitro study was to investigate and compare the analytical and practical use of Rivaroxaban monitoring with routine screening assays, thrombin generation and anti-Xa activity, in a clinical laboratory setting.
  
  
  METHODS
  Rivaroxaban was added to nine normal donor plasmas and to a normal pooled plasma in concentrations up to 1000 μg/L. Prothrombin time (PT), activated partial thromboplastin time (APTT), endogenous thrombin potential (ETP) and anti-Xa activity were measured in all donor samples. Responsiveness to Rivaroxaban and imprecision of Rivaroxaban recovery were assessed.
  
  
  RESULTS
  Low intra-, but high inter-individual imprecision was found for PT displaying a linear dose-response relationship. Imprecision was much lower when directly measuring anti-Xa activity. Responsiveness of ETP lag-time was high, but of total thrombin generation was low, illustrating that the main effect of Rivaroxaban Xa inhibition lies in delaying thrombin formation rather than in preventing it.
  
  
  CONCLUSIONS
  Despite a high inter-individual imprecision of the PT, this relatively fast and cost-friendly assay is sensitive to Rivaroxaban and integrates its effects on the global coagulant state of patients. Anti-Xa activity assays can be run to assess the actual Rivaroxaban concentration and in the future ETP could serve as a fine-tuned hemostatic balance indicator for patients using Rivaroxaban.
authors.affiliation: Hematological Clinical Chemistry Laboratory, Onze Lieve Vrouwe Gasthuis, Amsterdam, The Netherlands.
authors.forename: Pascal J
authors.initials: PJ
authors.lastname: Molenaar
authors.forename: Jasper
authors.initials: J
authors.lastname: Dinkelaar
authors.forename: Anja
authors.initials: A
authors.lastname: Leyte
mesh_terms: D000925:Anticoagulants / Q000097:blood / Q000494:pharmacology; D001774:Blood Chemical Analysis / Q000379:methods*; D001780:Blood Coagulation Tests / Q000379:methods*; D001782:Blood Donors; D002138:Calibration; D065427:Factor Xa Inhibitors; D006801:Humans; D009025:Morpholines / Q000097:blood* / Q000494:pharmacology*; D000069552:Rivaroxaban; D013876:Thiophenes / Q000097:blood* / Q000494:pharmacology*; D013917:Thrombin / Q000096:biosynthesis*
chemical_list: D000925:Anticoagulants; D065427:Factor Xa Inhibitors; D009025:Morpholines; D013876:Thiophenes; D000069552:Rivaroxaban; D013917:Thrombin