Perioperative Management of DOACs: Key Points
The following are key points to remember from a review on perioperative management of patients taking direct oral anticoagulants (DOACs):
- DOACs, including apixaban, dabigatran, edoxaban, and rivaroxaban, are the leading oral anticoagulants for common thromboembolic conditions, including atrial fibrillation and venous thromboembolism.
- Elimination half-lives for the oral factor Xa inhibitors (apixaban, edoxaban, rivaroxaban) are 8-12 hours in patients with a creatinine clearance (CrCl) ≥30 mL/min. Dabigatran (the oral direct thrombin inhibitor) has a half-life of 10-14 hours in patients with a CrCl ≥50 mL/min and 18-24 hours in patients with a CrCl 30-49.9 mL/min. All DOACs have a rapid onset of anticoagulant effect with a peak action of 2-3 hours after intake.
- Facilitating communication among various health care team members is critical for safe perioperative management of anticoagulants. This may include use of standardized protocols built into the electronic health record or the support of anticoagulation stewardship services (either in person or virtual care models).
- When selecting a therapeutic plan for perioperative DOAC management, clinicians should categorize the risk of bleeding both related to the surgical procedure and based on patient risk factors (e.g., history of prior bleeding, active cancer).
- For some low bleeding risk procedures, such as catheter ablation of atrial fibrillation and cardiac device implantation, continuation of uninterrupted DOAC therapy is preferred to interruption due to lower rates of major bleeding and systemic thromboembolism.
- For patients undergoing minimal bleeding risk procedures (e.g., dental extraction, skin lesion removal), omitting a single dose of DOAC either on the day of or the evening prior to the procedure is recommended.
- For patients undergoing a low-to-moderate bleeding risk procedure (e.g., cholecystectomy, inguinal hernia repair), it is recommended to skip the DOAC dose 1 day pre-procedure (~30-36 hours [~3 half-lives]) to minimize residual anticoagulant effect at the time of the procedure.
- For patients undergoing higher risk surgical procedures (e.g., major joint replacement, cancer surgery), it is recommended to hold a factor Xa inhibitor (apixaban, edoxaban, rivaroxaban) for 2 days pre-procedure (~60-68 hours [~5 half-lives]). For patients using dabigatran, they should hold the dose 2-4 days pre-procedure, depending on their baseline renal function. This approach has been tested in the prospective PAUSE trial of 3,007 DOAC-treated patients undergoing surgical procedures and shown to have a low rate of major bleeding in all cohorts.
- For patients undergoing neuraxial anesthesia or procedures, the American Society of Regional Anesthesia and Pain Medicine recommends that DOACs be discontinued for 3 days preoperatively for oral factor Xa inhibitors (apixaban, edoxaban, rivaroxaban) and for 4 days preoperatively for dabigatran.
- Following the surgical procedure, the DOAC is resumed based on the bleeding risk associated with the procedure and the patient’s underlying risk factors. Typically, DOACs are resumed 1-3 days postoperatively, but not before 24 hours postoperatively.
- There is no well-established DOAC level that corresponds to perioperative bleeding risk. Therefore, routine preoperative evaluation of DOAC levels is not recommended by major society guidelines (e.g., American College of Chest Physicians).
- There is no role for heparin or low-molecular-weight heparin bridging for patients using DOAC medications because the number of days without anticoagulation is quite small. For patients undergoing a high bleeding risk procedure (e.g., major joint replacement surgery), prophylactic heparin can be considered postoperatively until the DOAC medication is resumed.
- Patients undergoing emergent surgical procedures who are using DOAC therapy may experience an increased risk of major bleeding (17-23%) and arterial thromboembolism (7-16%). Prothrombin complex concentrates can be used to reverse the effect of all DOACs. Idarucizumab can be used to reverse dabigatran, while andexanet alfa can be used to reverse the oral factor Xa inhibitors (apixaban, edoxaban, and rivaroxaban). In some studies of andexanet alfa use for treatment of DOAC-associated intracranial hemorrhage, there was a high rate of ischemic stroke and thrombotic events as compared to usual care, suggesting this agent should be used with caution and anticoagulation resumption (either prophylactic or therapeutic intensity) should be initiated as soon as possible.
