Using a low-molecular weight heparin-calibrated anti-factor Xa assay to assess the concentration of apixaban and rivaroxaban

Int J Lab Hematol. 2022 Feb;44(1):163-167. doi: 10.1111/ijlh.13692. Epub 2021 Sep 15.

Abstract

Introduction: Direct oral anticoagulant (DOAC)-inhibiting factor Xa (FXa-DOAC) are being increasingly used as prophylaxis of venous thromboembolism and for prevention of stroke in patients with atrial fibrillation. In contrast to vitamin K antagonists, DOACs do not require monitoring in general. However, it is sometimes of value in the acute setting, for instance when considering a reversal agent in uncontrolled bleeding in patients on DOAC.

Methods: We evaluated if a low-molecular weight heparin (LMWH)-calibrated anti-factor Xa assay could be used to estimate FXa-DOAC concentration in the concentration range <100 ng/mL by spiking known concentrations of FXa-DOAC and from those result calculate the FXa-DOAC concentration from the response of the LMWH assay. This procedure was then evaluated by comparing the result with a drug-calibrated chromogenic assay and liquid chromatography tandem mass spectrometry (LC-MS/MS) on clinical plasma samples from patients treated with apixaban or rivaroxaban.

Results: Although the measuring range was narrower for the LMWH-calibrated assay, concentrations recalculated from the LMWH assay was comparable with those measured by the drug-calibrated method when compared with LC-MS/MS.

Conclusion: We suggest that an LMWH-calibrated anti-factor Xa assay can be used after characterization of the response of FXa-DOACs to give guidance on the concentration of apixaban and rivaroxaban. Shorter turnaround time than LC-MS/MS and the greater availability than drug-calibrated chromogenic assays could make this a valuable option in the acute setting.

Keywords: DOAC; LC-MS/MS; LMWH; apixaban; chromogenic assay; factor Xa inhibitors; rivaroxaban.

MeSH terms

  • Atrial Fibrillation / blood
  • Atrial Fibrillation / complications
  • Blood Coagulation Tests / methods*
  • Blood Coagulation Tests / standards
  • Chromatography, Liquid
  • Clinical Decision-Making
  • Disease Management
  • Disease Susceptibility
  • Drug Monitoring / methods
  • Factor Xa Inhibitors / administration & dosage
  • Factor Xa Inhibitors / pharmacokinetics*
  • Heparin, Low-Molecular-Weight
  • Humans
  • Pyrazoles / administration & dosage
  • Pyrazoles / pharmacokinetics*
  • Pyridones / administration & dosage
  • Pyridones / pharmacokinetics*
  • Reproducibility of Results
  • Rivaroxaban / administration & dosage
  • Rivaroxaban / pharmacokinetics*
  • Sensitivity and Specificity
  • Stroke / blood*
  • Stroke / diagnosis
  • Stroke / etiology
  • Stroke / prevention & control*
  • Tandem Mass Spectrometry
  • Venous Thromboembolism / blood*
  • Venous Thromboembolism / diagnosis
  • Venous Thromboembolism / etiology
  • Venous Thromboembolism / prevention & control*

Substances

  • Factor Xa Inhibitors
  • Heparin, Low-Molecular-Weight
  • Pyrazoles
  • Pyridones
  • apixaban
  • Rivaroxaban