[Direct Oral Anticoagulants (DOACs): Pharmacological Characteristics and Laboratory Assessment]

Vitamin K antagonists such as warfarin, which inhibit vitamin K-dependent clotting factors II, VII, IX, and X, have been the only available oral anticoagulants for more than 50 years. Direct oral anticoagulants (DOACs), including direct anti-Xa and a thrombin inhibitor, have been introduced and provide advantages over warfarin. DOACs are rapidly-acting, target-specific anticoagulants that inhibit both free and bound activated serine proteases, unlike heparin that can inhibit only free proteases. The FXa inhibitors (Rivaroxaban, Apixaban, Edoxaban) bind directly to the catalytic site of FXa and inhibit both free and prothrombinase-bound FXa. The thrombin inhibitor (Dabigatran), designed to occupy and inactivate the serine proteolytic pocket of thrombin, prevents thrombin from acting on fibrinogen to produce fibrin. Although routine coagulation mon- itoring of DOACs is not required, it may be useful under some circumstances. Several reports have de- scribed the effect of DOACs on routine assays including the APTT and PT. Dabigatran will interfere with most APTT-based and some PT-based assays, which means that laboratory testing will lead to results that are not representative of the physiologic effects. Rivaroxaban and edoxaban prolong the PT to a greater extent than APTT, and these agents may interfere with PT-based factor activity assays (FVII, X, V, and II) causing factitiously low activities. Also discussed are the use of drug-specific assays and alternative meth- ods to determine the relative drug concentration, such as evaluating drug calibrators in APTT and PT assays. The actual drug concentration may be required for specific patients, such as those with deterioration of the renal function, before surgical interventions, bleeding or thrombotic episodes, and suspected overdoses, and to control adherence to therapy. The need to assess DOACs in emergent situations as well as their impact on routine and special coagulation assays has created challenges in most laboratories. [Review] '.