title: Rivaroxaban: Quantification by anti-FXa assay and influence on coagulation tests: a study in 9 Swiss laboratories.
abstract: BACKGROUND
  Rivaroxaban (RXA) is licensed for prophylaxis of venous thromboembolism after major orthopaedic surgery of the lower limbs. Currently, no test to quantify RXA in plasma has been validated in an inter-laboratory setting. Our study had three aims: to assess i) the feasibility of RXA quantification with a commercial anti-FXa assay, ii) its accuracy and precision in an inter-laboratory setting, and iii) the influence of 10mg of RXA on routine coagulation tests.
  
  
  METHODS
  The same chromogenic anti-FXa assay (Hyphen BioMed) was used in all participating laboratories. RXA calibrators and sets of blinded probes (aim ii.) were prepared in vitro by spiking normal plasma. The precise RXA content was assessed by high-pressure liquid chromatography-tandem mass spectrometry. For ex-vivo studies (aim iii), plasma samples from 20 healthy volunteers taken before and 2 - 3hours after ingestion of 10mg of RXA were analyzed by participating laboratories.
  
  
  RESULTS
  RXA can be assayed chromogenically. Among the participating laboratories, the mean accuracy and the mean coefficient of variation for precision of RXA quantification were 7.0% and 8.8%, respectively. Mean RXA concentration was 114±43μg/L .RXA significantly altered prothrombin time, activated partial thromboplastin time, factor analysis for intrinsic and extrinsic factors. Determinations of thrombin time, fibrinogen, FXIII and D-Dimer levels were not affected.
  
  
  CONCLUSIONS
  RXA plasma levels can be quantified accurately and precisely by a chromogenic anti-FXa assay on different coagulometers in different laboratories. Ingestion of 10mg RXA results in significant alterations of both PT- and aPTT-based coagulation assays.
authors.affiliation: Division of Hematology, University Hospital and University of Zurich, Zurich, Switzerland. lars.asmis@unilabs.com
authors.forename: L M
authors.initials: LM
authors.lastname: Asmis
authors.forename: L
authors.initials: L
authors.lastname: Alberio
authors.forename: A
authors.initials: A
authors.lastname: Angelillo-Scherrer
authors.forename: W
authors.initials: W
authors.lastname: Korte
authors.forename: A
authors.initials: A
authors.lastname: Mendez
authors.forename: G
authors.initials: G
authors.lastname: Reber
authors.forename: B
authors.initials: B
authors.lastname: Seifert
authors.forename: H
authors.initials: H
authors.lastname: Stricker
authors.forename: D A
authors.initials: DA
authors.lastname: Tsakiris
authors.forename: W A
authors.initials: WA
authors.lastname: Wuillemin
mesh_terms: D000328:Adult; D000925:Anticoagulants / Q000097:blood; D016477:Artifacts; D001780:Blood Coagulation Tests / Q000379:methods*; D016903:Drug Monitoring / Q000379:methods*; D065427:Factor Xa Inhibitors; D006801:Humans; D008297:Male; D009025:Morpholines / Q000097:blood*; D015203:Reproducibility of Results; D000069552:Rivaroxaban; D012680:Sensitivity and Specificity; D013557:Switzerland; D013876:Thiophenes / Q000097:blood*
chemical_list: D000925:Anticoagulants; D065427:Factor Xa Inhibitors; D009025:Morpholines; D013876:Thiophenes; D000069552:Rivaroxaban