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The first direct oral anticoagulant (DOAC) to be approved for clinical use was dabigatran, a direct thrombin inhibitor, in 2010. Since that time, four additional DOACs, all direct anti-Xa inhibitors, have been approved, including rivaroxaban, apixaban, edoxaban and betrixaban. Our knowledge about the effect of DOACs on laboratory testing, as well as the use of the laboratory for measuring DOACs has been an evolving process. These drugs are not routinely monitored in the same fashion as coumadin, but there is an increasing demand on the laboratory to have the capacity to adequately assess DOAC anticoagulant effect (pharmacodynamics) or levels (pharmacokinetics) in either emergent or the routine situations. This manuscript provides an update on laboratory guidance and progress of methods for measuring DOACs.