Introduction

An increasing number of patients receive chronic oral anticoagulant (OAC) therapy to mitigate the risk of thromboembolic complications due to atrial fibrillation (AF), mechanical heart valves, or history of venous thromboembolism (VTE). Internists, cardiologists, hematologists, anesthesiologists, and surgeons often care for such patients who need to undergo elective or emergent medical procedures. The balance between the risk of thromboembolism and the risk of bleeding should be carefully maintained and fine‑tuned perioperatively in order to maximize benefits and minimize risks.^1,2 This review discusses the commonly used anticoagulants prescribed during the periprocedural period with a focus on appropriate considerations for regional anesthesia. Several societies have recently updated their guidelines on the subject, including the American Society of Regional Anesthesia and Pain Medicine (ASRA) and the European Society of Anaesthesiology (ESA).^3-5

Oral anticoagulants pharmacology

Vitamin K antagonists (VKA), warfarin and acenocoumarol, block the synthesis of the vitamin K–dependent clotting factors (II, VII, IX, and X). Rapidly absorbed from the gastrointestinal tract, their blood levels peak a few hours after administration. As compared to warfarin, which has a long half‑life of 36 to 42 hours, acenocoumarol has a shorter half‑life of 8 to 11 hours.^6,7 The anticoagulant effect is monitored by the prothrombin time (PT) or target international normalized ratio (INR) values. An INR of less than 1.1 is considered normal in healthy patients; however, some data point towards almost normal coagulation factor levels with an INR close to 2 (30% clotting factor activity).⁸

It should be noted that the INR may not reflect a decrease in all vitamin K–dependent clotting factors simultaneously. When starting or stopping warfarin, the INR value initially mirrors the activity of factor VII (half‑life, 6–8 hours), with 5 days being necessary for all coagulation factors to decrease to less than 40% or increase to more than 40%, respectively. Moreover, at the start of warfarin therapy, there is an initial prothrombotic state (conferred by decreases in levels of vitamin K–dependent natural anticoagulation factors protein C and S). Therefore, in patients who need to be rapidly therapeutically anticoagulated with warfarin, a bridging agent may be necessary for the first few days. For most indications, an INR of 2 to 3 is recommended. Patients at high thrombotic risk, such as patients with mechanical mitral valves, older generation aortic mechanical valves (Starr Edwards or ball‑in‑cage), and mechanical valves who recently had stroke (<6 months) should be maintained at a higher INR of 2.5 to 3.5.

In the past decade, direct oral anticoagulants (DOACs) have been introduced to the market and have increasingly replaced VKAs for many indications. These include the direct thrombin inhibitor, dabigatran, as well as several anti–factor Xa agents such as: rivaroxaban, apixaban, edoxaban, and betrixaban (table 1). As compared with warfarin, all DOACs have a rapid onset of action and peak serum level achieved within 1 to 4 hours. Moreover, all DOACs have a component of renal excretion, which affects the drugs’ half‑life. In addition to the traditional indications, factor Xa inhibitors (with the exception of betrixaban) have also been studied in patients with cancer, where they were found to be noninferior in comparison with low‑molecular‑weight heparin (LMWH).^9-11 All DOACs with their clinical indications and relevant pharmacokinetic properties are presented in table 1.^12-18