AbstractA new generation of antithrombotic agents, which are conventionally known as direct oral anticoagulants (DOACs), have recently emerged and are continuing to be developed. These provide direct inhibition of either thrombin (factor IIa; FIIa) or activated factor X (FXa) and currently include dabigatran (FIIa inhibitor) and rivaroxaban, apixaban, and edoxaban (FXa inhibitors). The dogma that DOACs do not require laboratory monitoring is countered by ongoing recognition that laboratory testing for drug effects is needed in many situations. In this review, we summarize the background to establishment of DOACs, assess which tests were found to be useful to screen for or quantitate drug effects/levels, and then review published guidelines/recommendations to assess concordance. In brief, (a) for the anti-FIIa agent dabigatran, the recommended screening assays are activated partial thromboplastin time (APTT) and/or thrombin time (TT), and the quantitative assays (using a dabigatran standard) are dilute TT/direct thrombin inhibitor assay (Hemoclot thrombin inhibitor) or an ecarin-based assay such as the ecarin clot time (ECT); (b) for the anti-FXa agent rivaroxaban, the recommended screening assay is the prothrombin time (PT), but this was not endorsed by all guidelines, and the quantitative assay (using a specific rivaroxaban standard) is an anti-FXa assay; (c) for the anti-FXa agent apixaban, the general insensitivity of PT and APTT prevented most groups from providing recommendation, and instead there was generalized support for direct quantitative assessment using anti-FXa assays and specific apixaban standard; (d) there is insufficient data for other direct anti-FXa agents and limited guidance in the literature.