title: Evaluation of the anti-factor Xa chromogenic assay for the measurement of rivaroxaban plasma concentrations using calibrators and controls.
abstract: Rivaroxaban is an oral, direct factor Xa inhibitor. Routine coagulation monitoring is not required, but a quantitative determination of rivaroxaban concentrations might be useful in some clinical circumstances. This multicentre study assessed the suitability of the anti-factor Xa chromogenic assay for the measurement of rivaroxaban plasma concentrations (ng/ml) using rivaroxaban calibrators and controls, and the inter-laboratory precision of the measurement. Twenty-four centres in Europe and North America were provided with sets of rivaroxaban calibrators (0, 41, 209 and 422 ng/ml) and a set of rivaroxaban pooled human plasma controls (20, 199 and 662 ng/ml; the concentrations were unknown to the participating laboratories). The evaluation was carried out over 10 days by each laboratory using local anti-factor Xa reagents as well as the centrally provided reagent, a modified STA® Rotachrom® assay. A calibration curve was produced each day, and the day-to-day precision was evaluated by testing three human plasma controls. When using the local anti-factor Xa reagents, the mean rivaroxaban concentrations (measured/actual values) were: 17/20, 205/199 and 668/662 ng/ml, and the coefficient of variance (CV) was 37.0%, 13.7% and 14.1%, respectively. When the modified STA Rotachrom method was used, the measured/actual values were: 18/20, 199/199 and 656/662 ng/ml, and the CV was 19.1%, 10.9% and 10.0%, respectively. The results suggest that, by using rivaroxaban calibrators and controls, the anti-factor Xa chromogenic method is suitable for measuring a wide range of rivaroxaban plasma concentrations (20-660 ng/ml), which covers the expected rivaroxaban plasma levels after therapeutic doses.
authors.affiliation: Hôtel-Dieu University Hospital, Paris, France. meyermichel.samama@biomnis.com
authors.forename: Meyer Michel
authors.initials: MM
authors.lastname: Samama
authors.forename: Genevieve
authors.initials: G
authors.lastname: Contant
authors.forename: Theodore E
authors.initials: TE
authors.lastname: Spiro
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Perzborn
authors.forename: Céline
authors.initials: C
authors.lastname: Guinet
authors.forename: Yves
authors.initials: Y
authors.lastname: Gourmelin
authors.forename: Léna
authors.initials: L
authors.lastname: Le Flem
authors.forename: Gabriele
authors.initials: G
authors.lastname: Rohde
authors.forename: Jean Luc
authors.initials: JL
authors.lastname: Martinoli
mesh_terms: D000925:Anticoagulants / Q000097:blood* / Q000494:pharmacology / Q000627:therapeutic use; D001774:Blood Chemical Analysis / Q000379:methods* / Q000592:standards; D002138:Calibration; D002863:Chromogenic Compounds / Q000737:chemistry; D005060:Europe; D065427:Factor Xa Inhibitors; D005240:Feasibility Studies; D006801:Humans; D009025:Morpholines / Q000097:blood* / Q000494:pharmacology / Q000627:therapeutic use; D009656:North America; D015588:Observer Variation; D015203:Reproducibility of Results; D000069552:Rivaroxaban; D012680:Sensitivity and Specificity; D013876:Thiophenes / Q000097:blood* / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: D000925:Anticoagulants; D002863:Chromogenic Compounds; D065427:Factor Xa Inhibitors; D009025:Morpholines; D013876:Thiophenes; D000069552:Rivaroxaban