Apixaban, Dabigatran, Edoxaban, Rivaroxaban
NB: Due to the complexity of DOAC management in the perioperative period and recent publication of new evidence, this monograph is under continual review and will be updated accordingly
Issues for Surgery
Risk of venous thromboembolism if omitted.
Risk of cerebrovascular event (CVA) if omitted.
Risk of bleeding and / or complications of bleeding if continued.
Advice in the Perioperative period
Elective Surgery / Procedures
Perioperative DOAC decision-making should take into account the patient’s underlying thrombotic risk balanced against the bleeding risk associated with the surgery / procedure – see Anticoagulants (Oral) – A General Overview.
Assessment of Renal Function
DOACs have stable pharmacokinetics and a predictable elimination half-life. If the decision is made to interrupt DOAC therapy, the patient’s current renal function should be used to guide when to stop DOAC therapy.
The Cockcroft-Gault creatinine clearance (also see calculation below) should be used to accurately calculate renal function. The eGFR may overestimate renal function, particularly in elderly or underweight patients and must not be used.
Use of DOAC therapy is contra-indicated if creatinine clearance (CrCl) < 15 ml/min (< 30ml/min for dabigatran) and any patient found to have a CrCl that contra-indicates the use of the DOAC should be immediately referred to a Haematologist. If there is any doubt as to the safe management of DOAC therapy in patients with reduced renal function (particularly CrCl < 30 ml/min), the advice of a Haematologist should be sought.
Minor Bleeding Risk Surgery / Procedures
For examples of minor bleeding risk surgery / procedures – see Anticoagulants (Oral)– A General Overview.
General Surgical Procedures (High / Low Risk Bleeding)
Follow the advice in figure 1 below.
Figure 1: Number of doses of DOAC to be omitted prior to general surgical procedures2
* Low dose Rivaroxaban (2.5mg Twice Daily) is licensed for use in conjunction with aspirin +/- clopidogrel3. Refer to individual monographs for the perioperative management of aspirin and clopidogrel and discuss arterial thrombotic risk with a cardiologist or vascular surgeon (depending on indication for therapy). Pre-operative cessation of low-dose rivaroxaban has not been studied and patients should be managed on a case-by-case basis.
Endoscopy / Interventional Procedures
NB: Due to publication of the British Society of Gastroenterology and European Society of Gastrointestinal Endoscopy 2021 update for 'Endoscopy in Patients on antiplatelet or anticoagulant therapy, including direct oral anticoagulants'. This section has been temporarily removed while it is revised. Sorry for any convenience caused while we await this update.
Prophylactic dose LMWH may be considered in the post-operative period prior to DOAC resumption (see under Post-operative Advice below).
Emergency Surgery / Procedures
If there is not sufficient time to follow the guidance for elective surgery / procedures as above:
Neuraxial (Spinal / Epidural) Anaesthesia or Lumbar Punctures
Continuation of DOACs in patients who receive neuraxial anaesthesia is not recommended due to the risk of spinal haematoma13.
Indwelling Catheter Removal Advice
Figure 3: Advice on timings of DOAC doses in relation to removal of an indwelling catheter13.
*It is recommended that in the event of traumatic puncture, the administration of rivaroxaban should be delayed for 24 hours3. Although not recommended by other DOAC manufacturers, consideration should be given to delaying administration of all DOACs by 24 hours in the event of traumatic puncture.
NB: All DOACs are rapidly absorbed and have a rapid onset of action, with peak anticoagulant activity at approximately 2-3 hours after oral ingestion. Attention to post-operative haemostasis is clinically important since too early resumption of DOACs, especially within 24 hours of surgery, is associated with a two- to fourfold increased risk of major bleeding5.
Minor / Low Risk Procedures
High Risk Procedures / Increased Bleeding Risk
Consider prophylactic LMWH, commenced 6-12 hours post-op based on patient’s thromboembolic risk and bleeding risk.
LMWH should be discontinued immediately upon recommencing DOAC.
Patients Who Have Received Idarucizumab
If necessary, alternative antithrombotic therapy (e.g. LMWH) can be started at any time, if the patient is clinically stable and adequate haemostasis has been achieved8. Alternative antithrombotic therapy should be immediately discontinued upon recommencing dabigatran.
Patients Who Have Received Andexanet Alfa
Interaction(s) with Common Anaesthetic Agents
None relevant7, 11, 12, 15, 16, 17.
Interaction(s) with other Common Medicines used in the Perioperative Period
Non-Steroidal Anti-inflammatory Drugs (NSAIDs)
DOACs are predicted to increase the risk of bleeding when given with NSAIDs. Short-term post-operative use may be considered although caution is advised7, 11, 12, 15, 16, 17. Consider appropriate use of a gastroprotective agent (e.g. proton pump inhibitor).
Low Molecular Weight Heparin (LWMH) / Unfractionated Heparin (UFH)
DOACs and LMWH / UFH can increase the risk of bleeding15. Concomitant use is contraindicated unless under specific circumstances and advised by a specialist7, 11, 12, 16. Prophylactic LMWH should be discontinued immediately upon recommencing DOAC.
Erythromycin (via CYP3A4 and P-gp inhibition) increases the exposure to edoxaban – the manufacturer advises a reduction in the edoxaban dose (see current product literature)16, 17. Clarithromycin may increase the exposure to edoxaban. Consideration may be given to reducing the dose of edoxaban, although the manufacturer makes no specific recommendation17.
Erythromycin and clarithromycin may increase the exposure to apixaban and dabigatran7, 11, 17. The patient should be monitored for excessive bleeding if either erythromycin or clarithromycin are co-administered with a DOAC17.
It is recommended to monitor the patient for signs of excessive bleeding if co-administration of erythromycin or clarithromycin with a DOAC is necessary17.
Whilst single surgical prophylactic doses should not pose a problem for most antimicrobials, continued post-operative treatment may require close monitoring. Consult current product literature.
Rationale for Perioperative Advice
The Perioperative Management of Patients with Atrial Fibrillation receiving a Direct Oral Anticoagulant Evaluation (PAUSE), published in August 2019, supports the use of a standardised perioperative DOAC management protocol, without LWMH bridging or measurement of coagulation function. The study findings show that this approach was associated with low rates of major bleeding and arterial thromboembolism2.
Information for Patients
All patients (carers if applicable) should receive written information in relation to the anticipated date of their procedure, including the date and time of their last dose of DOAC1. For an example patient information leaflet please click here.