A subset of direct oral anticoagulants (DOACs) directly inhibit coagulation factor Xa. These direct Xa inhibitors, including apixaban, edoxaban, and rivaroxaban, do not require routine laboratory monitoring. There are some clinical scenarios in which efficacy or safety may be a concern and a measurement of direct Xa inhibitor activity may be useful. Drug-specific anti-Xa activity assays calibrated for a single direct Xa inhibitor may be used to make quantitative measurements of drug level. There is currently no definitive clinical trial evidence for adjusting apixaban, edoxaban, or rivaroxaban dose based on an anti-Xa activity result.
While routine monitoring is not required, measurement of apixaban, edoxaban, or rivaroxaban levels may be helpful in contexts that would affect their safe and effective use, such as impaired absorption, drug interaction, treatment failure, or renal impairment. The following algorithm provides a testing strategy for measuring these direct Xa inhibitors. For additional information on reported trough and peak concentration ranges, see the On-Therapy Range Information table.
Clinical and/or Analytical Sensitivity
Lower limit of assay detection by drug:
- Apixaban: 23 ng/mL
- Edoxaban: 20 ng/mL
- Rivaroxaban: 25 ng/mL
- The On-Therapy Range Information table comes from published data (including pharmacokinetic studies and phase-three clinical trials ) and applies to adults ≥18 years of age. Trough and peak concentration ranges represent the median (eg, 5th-95th percentile) for the studied population; they are NOT meant to be interpreted as therapeutic concentration ranges.
- ARUP interpretive comments will include on-therapy ranges from published data regarding treatment of deep vein thrombosis (DVT) and pulmonary embolism (PE).
- Anti-Xa activity assays can only be used to accurately measure the specific drug for which they are calibrated (eg, apixaban can only be accurately measured in an anti-Xa assay that includes an apixaban calibrator).
- Anti-Xa activity results are not reliable when more than one drug with anti-Xa activity is present in a plasma sample. Any drug with activity against factor Xa (eg, unfractionated heparin, low molecular weight heparin, fondaparinux, apixaban, edoxaban, rivaroxaban) will show effect in any of the anti-Xa activity assays. That is, if more than one drug is present (eg, unfractionated heparin and rivaroxaban), the effects of both drugs will be detected in the anti-Xa activity assay, regardless of the drug for which the assay is calibrated.
- Grossly hemolyzed specimens are not suitable for testing due to potential coagulation factor activation and chromogenic assay interference.
- Grossly icteric samples are not suitable for testing as bilirubin may interfere with chromogenic assays.
Douxfils J, Adcock DM, Bates SM, et al. 2021 update of the International Council for Standardization in Haematology recommendations for laboratory measurement of direct oral anticoagulants. Thromb Haemost. 2021;121(8):1008-1020.
European Medicines Agency. Eliquis: summary of product characteristics. [Accessed: July 2021]
Mueck W, Stampfuss J, Kubitza D, et al. Clinical pharmacokinetic and pharmacodynamic profile of rivaroxaban. Clin Pharmacokinet. 2014;53(1):1-16.
Douxfils J, Ageno W, Samama CM, et al. Laboratory testing in patients treated with direct oral anticoagulants: a practical guide for clinicians. J Thromb Haemost. 2018;16(2):209-219.
Gosselin RC, Adcock DM, Bates SM, et al. International Council for Standardization in Haematology (ICSH) recommendations for laboratory measurement of direct oral anticoagulants. Thromb Haemost. 2018;118(3):437-450.