Evaluation of the anti-factor Xa chromogenic assay for the measurement of rivaroxaban plasma concentrations using calibrators and controls

Thromb Haemost. 2012 Feb;107(2):379-87. doi: 10.1160/TH11-06-0391. Epub 2011 Dec 21.

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.

Publication types

  • Evaluation Study
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anticoagulants / blood*
  • Anticoagulants / pharmacology
  • Anticoagulants / therapeutic use
  • Blood Chemical Analysis / methods*
  • Blood Chemical Analysis / standards
  • Calibration
  • Chromogenic Compounds / chemistry
  • Europe
  • Factor Xa Inhibitors
  • Feasibility Studies
  • Humans
  • Morpholines / blood*
  • Morpholines / pharmacology
  • Morpholines / therapeutic use
  • North America
  • Observer Variation
  • Reproducibility of Results
  • Rivaroxaban
  • Sensitivity and Specificity
  • Thiophenes / blood*
  • Thiophenes / pharmacology
  • Thiophenes / therapeutic use

Substances

  • Anticoagulants
  • Chromogenic Compounds
  • Factor Xa Inhibitors
  • Morpholines
  • Thiophenes
  • Rivaroxaban