title: Comparison of anti-Xa and dilute Russell viper venom time assays in quantifying drug levels in patients on therapeutic doses of rivaroxaban.
abstract: BACKGROUND
  Rivaroxaban is a new oral anticoagulant that functions as a direct anti-Xa inhibitor. Although routine monitoring is not required, measurement of plasma concentrations may be necessary in certain clinical situations. Routine coagulation assays, such as the prothrombin time and, to a lesser degree, activated partial thromboplastin time, correlate with drug concentration, but because of reagent variability, these methods are not reliable for determining rivaroxaban anticoagulation.
  
  
  OBJECTIVE
  To compare different methods and calibrators for measuring rivaroxaban, including the chromogenic anti-Xa assay, which, when calibrated with a rivaroxaban standard, may be more appropriate for determining anticoagulation.
  
  
  METHODS
  We compared measured rivaroxaban concentrations with the same anti-Xa kit but used different calibrators, with different anti-Xa kits but the same calibrators, with antithrombin-supplemented anti-Xa kit versus nonsupplemented kits, and with 2 methods based on rivaroxaban-calibrated, high-phospholipid, dilute Russell viper venom time. Regression and paired t test statistics were used to determine correlation and significant differences among methods and calibrator sources.
  
  
  RESULTS
  Although there was strong correlation, statistically significant biases existed among methods that report rivaroxaban levels. A single-source calibrator did not alleviate those differences among methods. High-phospholipid Russell viper venom reagents correlated with rivaroxaban concentration but were not better than chromogenic anti-Xa methods.
  
  
  CONCLUSIONS
  Rivaroxaban-calibrated, anti-Xa measurements correlate well, but the clinical significance of the variation with rivaroxaban measurements is uncertain. The antithrombin-supplemented, anti-Xa method should be avoided for measuring rivaroxaban.
authors.affiliation: From the Department of Pathology and Laboratory Medicine, University of California, Davis Health System, Sacramento (Mr Gosselin); Colorado Coagulation, Corporation of America Holdings, Englewood (Dr Funk and Mr Taylor); the Departments of Pharmacy (Drs Francart, Hawes, and Moll) and Family Medicine (Dr Hawes) and the Hemophilia and Thrombosis Center (Dr Moll), University of North Carolina, Chapel Hill, NC; and the Hemostasis Reference Laboratory, Blood Center of Wisconsin, Milwaukee (Dr Friedman).
authors.forename: Robert C
authors.initials: RC
authors.lastname: Gosselin
authors.forename: Dorothy M
authors.initials: DM
authors.lastname: Adcock Funk
authors.forename: J Michael
authors.initials: JM
authors.lastname: Taylor
authors.forename: Suzanne J
authors.initials: SJ
authors.lastname: Francart
authors.forename: Emily M
authors.initials: EM
authors.lastname: Hawes
authors.forename: Kenneth D
authors.initials: KD
authors.lastname: Friedman
authors.forename: Stephan
authors.initials: S
authors.lastname: Moll
mesh_terms: D001780:Blood Coagulation Tests / Q000379:methods*; D065427:Factor Xa Inhibitors / Q000097:blood*; D006801:Humans; D009025:Morpholines / Q000097:blood*; D010314:Partial Thromboplastin Time; D011517:Prothrombin Time; D000069552:Rivaroxaban; D013876:Thiophenes / Q000097:blood*
chemical_list: D065427:Factor Xa Inhibitors; D009025:Morpholines; D013876:Thiophenes; D000069552:Rivaroxaban