title: Heparin-Calibrated Chromogenic Anti-Xa Activity Measurements in Patients Receiving Rivaroxaban: Can This Test Be Used to Quantify Drug Level?
abstract: BACKGROUND
  Determination of plasma rivaroxaban concentration may be necessary in certain clinical situations. Rivaroxaban concentration can be accurately and rapidly determined using a chromogenic anti-activated factor X (factor Xa) assay with specific drug calibrator material. However, there are currently no Food and Drug Administration (FDA)-approved rivaroxaban calibrators available in the United States.
  
  
  OBJECTIVE
  To determine whether FDA-approved commercial kits for measuring heparin anti-factor Xa activity can be used to assess rivaroxaban concentrations when calibrated for unfractionated heparin or low-molecular-weight heparins.
  
  
  METHODS
  Trough and peak samples were taken from 30 patients taking rivaroxaban as part of their routine care for atrial fibrillation or venous thromboembolism. The samples were tested using 3 different FDA-approved commercial kits for measuring heparin anti-factor Xa activity.
  
  
  RESULTS
  There was acceptable correlation between rivaroxaban levels and heparin anti-factor Xa activity using Berichrom and COAMATIC heparin kits. The STA liquid heparin method was the most sensitive to presence of rivaroxaban.
  
  
  CONCLUSIONS
  This study demonstrates a strong correlation, but variability between kits, for assessing rivaroxaban concentrations using heparin anti-factor Xa assays. The extent of the heparin calibration curve significantly limits the measurable rivaroxaban range, and this application may be useful only for trough samples. The STA liquid heparin, being exquisitely sensitive to rivaroxaban, may be suitable for ruling out presence of the drug. The routine use of heparin-calibrated anti-factor Xa assays to quantify rivaroxaban is not advocated, and when applied, it must be used with caution and limitations clearly understood.
authors: University of California, Sacramento, CA, USA.
authors: Robert C
authors: RC
authors: Gosselin
authors: University of North Carolina, Chapel Hill, NC, USA.
authors: Suzanne J
authors: SJ
authors: Francart
authors: University of North Carolina, Chapel Hill, NC, USA.
authors: Emily M
authors: EM
authors: Hawes
authors: University of North Carolina School of Medicine, Chapel Hill, NC, USA.
authors: Stephan
authors: S
authors: Moll
authors: University of California, Sacramento, CA, USA.
authors: William E
authors: WE
authors: Dager
authors: Laboratory Corporation of America® Holdings, Englewood, CO, USA adcockd@labcorp.com.
authors: Dorothy M
authors: DM
authors: Adcock
mesh_terms: D001281:Atrial Fibrillation / Q000517:prevention & control; D002138:Calibration; D002863:Chromogenic Compounds; D015951:Factor Xa / Q000032:analysis; D065427:Factor Xa Inhibitors / Q000097:blood* / Q000627:therapeutic use; D005260:Female; D006493:Heparin / Q000097:blood*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011933:Reagent Kits, Diagnostic; D000069552:Rivaroxaban / Q000097:blood* / Q000627:therapeutic use; D014481:United States; D054556:Venous Thromboembolism / Q000517:prevention & control
chemical_list: D002863:Chromogenic Compounds; D065427:Factor Xa Inhibitors; D011933:Reagent Kits, Diagnostic; D006493:Heparin; D000069552:Rivaroxaban; D015951:Factor Xa
keywords: anti-Xa; concentration; heparin; laboratory; rivaroxaban