title: Is anti-factor Xa chromogenic assay for Rivaroxaban appropriate in clinical practice? Advantages and comparative drawbacks.
abstract: BACKGROUND
  No routine monitoring is required with factor Xa inhibitor rivaroxaban. Yet, its titration must be adapted, and its misuse may lead to increased risk of bleeding; therefore, therapeutic rivaroxaban monitoring might help in specific situations.
  
  
  METHODS
  As asked by clinicians of our medical center, we measured rivaroxaban plasma concentrations in real conditions of use and checked their corresponding prescriptions. Measurement of 112 samples from 94 consecutive patients was performed with a Biophen LRT® anti-Xa chromogenic assay and compared blindly to the HPLC-MSMS "gold standard" method. Rivaroxaban was effectively given to 80 out of 94 patients but a mere 57% through an adequate prescription (within the scope of indications/titration). All chromogenic measurements were over the pre-specified 30ng/ml LOQ, whereas only 98 /114 samples had quantifiable rivaroxaban with HPLC-MSMS (LOQ 1ng/ml). Correlation between the two methods and linear regression were highly significant (p<0.0001). However, chromogenic values (mean 141.6ng/ml[96.6]) overestimated HPLC-MSMS values (119.7ng/ml[79.5]) by 22ng/ml according to Bland-Altman analysis (p<0.001). After re-assessing the chromogenic LOQ at 52ng/ml, 83 quantifiable samples had a mean concentration of 176.9ng/ml as compared to 158.5ng/ml with HPLC-MSMS, with no false positive anymore.
  
  
  CONCLUSIONS
  In our medical center, rivaroxaban concentrations could be assessed by a rapid chromogenic method. Its pre-specified LOQ proved too high after being checked "on site" against HPLC-MSMS. Prescriptions for rivaroxaban were not optimal. An overestimated LOQ may impair observance monitoring or predispose patients to either risky thrombolysis or otherwise adjournable surgery in clinical practice.
authors.affiliation: Regional Center of Pharmacovigilance « Nice-Alpes-Côte d'Azur », Cimiez Hospital, Nice, France; University of Nice Medical Center, Dept of Pharmacology, Pasteur Hospital, Nice, France.
authors.forename: Guillaume
authors.initials: G
authors.lastname: Bardy
authors.affiliation: University of Nice Medical Center, Dept of Haematology, Pasteur Hospital, Nice, France.
authors.forename: Florence
authors.initials: F
authors.lastname: Fischer
authors.affiliation: University of Nice Medical Center, Dept of Haematology, Pasteur Hospital, Nice, France.
authors.forename: Anny
authors.initials: A
authors.lastname: Appert
authors.affiliation: Regional Center of Pharmacovigilance « Nice-Alpes-Côte d'Azur », Cimiez Hospital, Nice, France.
authors.forename: Bernadette
authors.initials: B
authors.lastname: Baldin
authors.affiliation: Regional Center of Pharmacovigilance « Nice-Alpes-Côte d'Azur », Cimiez Hospital, Nice, France.
authors.forename: Marie
authors.initials: M
authors.lastname: Stève
authors.affiliation: Regional Center of Pharmacovigilance « Nice-Alpes-Côte d'Azur », Cimiez Hospital, Nice, France.
authors.forename: Anne
authors.initials: A
authors.lastname: Spreux
authors.affiliation: University of Nice Medical Center, Dept of Pharmacology, Pasteur Hospital, Nice, France.
authors.forename: Thibaud
authors.initials: T
authors.lastname: Lavrut
authors.affiliation: Regional Center of Pharmacovigilance « Nice-Alpes-Côte d'Azur », Cimiez Hospital, Nice, France; University of Nice Medical Center, Dept of Pharmacology, Pasteur Hospital, Nice, France. Electronic address: drici.md@chu-nice.fr.
authors.forename: Milou-Daniel
authors.initials: MD
authors.lastname: Drici
mesh_terms: D000368:Aged; D001774:Blood Chemical Analysis / Q000379:methods*; D002863:Chromogenic Compounds / Q000737:chemistry; D003124:Colorimetry / Q000379:methods; D015951:Factor Xa / Q000032:analysis*; D065427:Factor Xa Inhibitors / Q000097:blood / Q000627:therapeutic use; D005260:Female; D006801:Humans; D008297:Male; D015203:Reproducibility of Results; D000069552:Rivaroxaban / Q000097:blood* / Q000633:toxicity*; D012680:Sensitivity and Specificity; D016037:Single-Blind Method; D013927:Thrombosis / Q000097:blood* / Q000175:diagnosis / Q000517:prevention & control*
chemical_list: D002863:Chromogenic Compounds; D065427:Factor Xa Inhibitors; D000069552:Rivaroxaban; D015951:Factor Xa
keywords: Anti-factor Xa; Anticoagulant; Chromogenic assay; HPLC-MSMS; Rivaroxaban