Laboratory Assessment of the Anticoagulant Activity of Direct Oral Anticoagulants: A Systematic Review

Bethany T. Samuelson, Adam Cuker, Deborah M. Siegal, Mark Crowther, David A. Garcia

Research output: Contribution to journalArticlepeer-review

238 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)127-138
Number of pages12
JournalCHEST
Volume151
Issue number1
DOIs
StatePublished - Jan 1 2017
Externally publishedYes

Keywords

  • antithrombotic therapy
  • deep venous thrombosis
  • direct oral anticoagulants
  • laboratory
  • pulmonary embolism

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Critical Care and Intensive Care Medicine
  • Cardiology and Cardiovascular Medicine

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