title: Laboratory Assessment of the Anticoagulant Activity of Direct Oral Anticoagulants: A Systematic Review.
abstract: BACKGROUND
  Direct oral anticoagulants (DOACs) are the treatment of choice for most patients with atrial fibrillation and/or noncancer-associated venous thromboembolic disease. Although routine monitoring of these agents is not required, assessment of anticoagulant effect may be desirable in special situations. The objective of this review was to summarize systematically evidence regarding laboratory assessment of the anticoagulant effects of dabigatran, rivaroxaban, apixaban, and edoxaban.
  
  
  METHODS
  PubMed, Embase, and Web of Science were searched for studies reporting relationships between drug levels and coagulation assay results.
  
  
  RESULTS
  We identified 109 eligible studies: 35 for dabigatran, 50 for rivaroxaban, 11 for apixaban, and 13 for edoxaban. The performance of standard anticoagulation tests varied across DOACs and reagents; most assays, showed insufficient correlation to provide a reliable assessment of DOAC effects. Dilute thrombin time (TT) assays demonstrated linear correlation (r2= 0.67-0.99) across a range of expected concentrations of dabigatran, as did ecarin-based assays. Calibrated anti-Xa assays demonstrated linear correlation (r2= 0.78-1.00) across a wide range of concentrations for rivaroxaban, apixaban, and edoxaban.
  
  
  CONCLUSIONS
  An ideal test, offering both accuracy and precision for measurement of any DOAC is not widely available. We recommend a dilute TT or ecarin-based assay for assessment of the anticoagulant effect of dabigatran and anti-Xa assays with drug-specific calibrators for direct Xa inhibitors. In the absence of these tests, TT or APTT is recommended over PT/INR for assessment of dabigatran, and PT/INR is recommended over APTT for detection of factor Xa inhibitors. Time since last dose, the presence or absence of drug interactions, and renal and hepatic function should impact clinical estimates of anticoagulant effect in a patient for whom laboratory test results are not available.
authors.affiliation: Department of Medicine, Division of Hematology, University of Washington, Seattle, WA. Electronic address: bts99@uw.edu.
authors.forename: Bethany T
authors.initials: BT
authors.lastname: Samuelson
authors.affiliation: Department of Medicine and Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA.
authors.forename: Adam
authors.initials: A
authors.lastname: Cuker
authors.affiliation: Department of Medicine, McMaster University, Hamilton, ON, Canada.
authors.forename: Deborah M
authors.initials: DM
authors.lastname: Siegal
authors.affiliation: Department of Medicine, McMaster University, Hamilton, ON, Canada.
authors.forename: Mark
authors.initials: M
authors.lastname: Crowther
authors.affiliation: Department of Medicine, Division of Hematology, University of Washington, Seattle, WA.
authors.forename: David A
authors.initials: DA
authors.lastname: Garcia
mesh_terms: D000991:Antithrombins / Q000494:pharmacology*; D001281:Atrial Fibrillation / Q000097:blood / Q000150:complications / Q000188:drug therapy*; D001777:Blood Coagulation / Q000187:drug effects; D016903:Drug Monitoring / Q000379:methods*; D006801:Humans; D054556:Venous Thromboembolism / Q000209:etiology / Q000517:prevention & control*
chemical_list: D000991:Antithrombins
keywords: antithrombotic therapy; deep venous thrombosis; direct oral anticoagulants; laboratory; pulmonary embolism