title: Comparison of the effects of apixaban and rivaroxaban on prothrombin and activated partial thromboplastin times using various reagents.
abstract: BACKGROUND
  Clinical situations occur where expedient assessment of the anticoagulant activity of the direct factor Xa (FXa) inhibitors is required. Although quantitative anti-FXa (FXa) assays can be used to measure plasma levels of apixaban or rivaroxaban, turnaround is often slow and many laboratories do not perform these assays.
  
  
  OBJECTIVE
  We compared the in vitro effects of apixaban and rivaroxaban on two readily available laboratory tests, the prothrombin time (PT) and activated partial thromboplastin time (APTT), performed with different reagents. We aimed to identify the most sensitive reagents.
  
  
  METHODS
  Rivaroxaban or apixaban was added to human plasma at a range of concentrations covering expected peak and trough levels, and concentrations were confirmed using calibrated anti-FXa assays. Samples were assayed with six PT and seven APTT reagents using different coagulometers.
  
  
  CONCLUSIONS
  TriniCLOT PT Excel S was the only reagent to demonstrate sensitivity to apixaban. All of the PT reagents were sensitive to rivaroxaban with TriniCLOT PT Excel S and HemosIL HS PLUS being the most sensitive. Sensitivity to rivaroxaban varied among APTT reagents; four reagents exhibited the greatest responsiveness, and of these, Actin FSL was the most responsive. Commonly used coagulation tests may be useful for assessing the anticoagulant effect of rivaroxaban but not of apixaban. The reason for the different effects of apixaban and rivaroxaban on the PT and APTT is unknown.
authors.affiliation: Sansom Institute for Health Research, University of South Australia, Adelaide, SA, Australia.
authors.forename: B J
authors.initials: BJ
authors.lastname: Dale
authors.forename: J S
authors.initials: JS
authors.lastname: Ginsberg
authors.forename: M
authors.initials: M
authors.lastname: Johnston
authors.forename: J
authors.initials: J
authors.lastname: Hirsh
authors.forename: J I
authors.initials: JI
authors.lastname: Weitz
authors.forename: J W
authors.initials: JW
authors.lastname: Eikelboom
mesh_terms: D001777:Blood Coagulation / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D065427:Factor Xa Inhibitors / Q000494:pharmacology*; D006801:Humans; D009025:Morpholines / Q000494:pharmacology*; D010314:Partial Thromboplastin Time / Q000379:methods*; D011237:Predictive Value of Tests; D011517:Prothrombin Time / Q000379:methods*; D011720:Pyrazoles / Q000494:pharmacology*; D011728:Pyridones / Q000494:pharmacology*; D015203:Reproducibility of Results; D000069552:Rivaroxaban; D013876:Thiophenes / Q000494:pharmacology*
chemical_list: D065427:Factor Xa Inhibitors; D009025:Morpholines; D011720:Pyrazoles; D011728:Pyridones; D013876:Thiophenes; C522181:apixaban; D000069552:Rivaroxaban
keywords: activated partial thromboplastin time; anticoagulants; apixaban; prothrombin time; rivaroxaban