Perioperative management of patients on direct oral anticoagulants

Abstract

Direct oral anticoagulants (DOACs) have been licensed worldwide for several years for various indications. Each year, 10–15% of patients on oral anticoagulants will undergo an invasive procedure and expert groups have issued several guidelines on perioperative management in such situations. The perioperative guidelines have undergone numerous updates as clinical experience of emergency management has increased and perioperative studies including measurement of residual anticoagulant levels have been published. The high inter-patient variability of DOAC plasma levels has challenged the traditional recommendation that perioperative DOAC interruption should be based only on the elimination half-life of DOACs, especially before invasive procedures carrying a high risk of bleeding. Furthermore, recent publications have highlighted the potential danger of heparin bridging use when DOACs are stopped before an invasive procedure.As antidotes are progressively becoming available to manage severe bleeding or urgent procedures in patients on DOACs, accurate laboratory tests have become the standard to guide their administration and their actions need to be well understood by clinicians.This review aims to provide a systematic approach to managing patients on DOACs, based on recent updates of various perioperative guidance, and highlighting the advantages and limits of recommendations based on pharmacokinetic properties and laboratory tests.

International consensus statement on the peri‐operative management of direct oral anticoagulants in cardiac surgery

“…Rivaroxaban is approved in the US, Canada and Europe for venous thromboembolism prophylaxis in orthopaedic surgery and for stroke prevention in non‐valvular AF. Recently, rivaroxaban also gained a license for the treatment of deep venous thrombosis and prevention of pulmonary embolism and atherothrombotic events after acute coronary syndrome with elevated cardiac biomarkers in Europe .…”

“…Andexanet alpha is a recombinant modified human FXa decoy that binds directly to FXa inhibitors and gained approval from the Food and Drug Administration (FDA) at the beginning of May 2018. The dosage that has been studied for the reversal of rivaroxaban 20 mg is an intravenous bolus of 800 mg followed by a continuous infusion of 8 mg.min −1 for 2 h (960 mg in total) . Ciraparantag acts through direct, non‐covalent binding of FXa inhibitors, and exhibits the potential to inhibit the effect of direct thrombin inhibitors.…”

“…Ciraparantag acts through direct, non‐covalent binding of FXa inhibitors, and exhibits the potential to inhibit the effect of direct thrombin inhibitors. Both agents might be considered as future antidotes for FXa inhibitors with promising characteristics .…”

“…In patients with CrCl between 15 and 30 ml.min −1 , the time of the last pre‐operative dose should be at least 2 days as a minimum, and/or individualised for patient and procedural factors for bleeding and thrombosis and anti‐FXa activity. Resumption of rivaroxaban therapy is recommended 2–3 days after the procedure . In cases of life‐threatening bleeding, apart from direct reversal agents, established methods for severe bleeding management, such as the use of PCC, allogeneic blood products and antifibrinolytics, are indicated .…”

A level‐headed approach to measuring direct oral anticoagulants: A 2‐year retrospective analysis of DOAC levels from a tertiary UK centre

“…Given this variation in trough DOAC level, it is recommended that patients stop taking their DOAC anywhere between 24 and 120 hours prior to surgery, depending on the DOAC, renal function, concomitant medication and bleeding risk . However, there are only limited studies assessing DOAC concentrations following a period of omission pre‐operatively .…”