Issues for surgery
For prevention or treatment of venous thromboembolism (VTE) - risk of VTE if omitted.
For prevention of stroke - risk of arterial embolism (e.g. cerebrovascular event, CVA) if omitted.
Risk of bleeding and / or complications of bleeding if continued.
Risk of epidural or spinal haematoma if continued prior to neuraxial anaesthesia.
Advice in the perioperative period
Elective surgery
Step 1 – determine indication
For deep vein thrombosis (DVT) or pulmonary embolism (PE) within last 3 months – refer to Haematologist to determine appropriate course of action.
Step 2 – determine if dose appropriate for patient
The guidance below assumes that the patient is on an appropriate dose of apixaban in relation to the indication, their renal function, age, weight, and concomitant interacting medication – see current product literature to establish that the patient is on the appropriate dose.
When estimating renal function use Cockcroft-Gault (C&G) creatinine clearance (CrCl) rather than estimated glomerular filtration rate (eGFR), to avoid overestimating renal function, particularly in the elderly or at extremes of body weight. It is recommended to use actual weight rather than ideal body weight.
Apixaban is not recommended if CrCl less than 15ml/min – such patients should be immediately referred to a Haematologist.
If there is any doubt as to whether the patient is on an appropriate dose, or if there is concern regarding patient specific factors such as CrCl < 30ml/min, weight < 50kg, concomitant use of interacting medication etc., advice should be sought from a Haematologist.
Step 3 – determine bleeding risk for surgery / procedure
For examples of minor, low / moderate and high bleeding risk surgical procedures and low and high-risk endoscopic procedures see Anticoagulants - Overview.
Step 4 – decision on pre-operative cessation
Minor bleeding risk surgery / procedure (not endoscopic)
Most minor bleeding risk procedures and those procedures where any bleeding is easily controllable, can be undertaken safely without apixaban interruption (where possible time the procedure for 12 hours after the last dose).
Low bleeding risk endoscopic procedure / low or moderate bleeding risk surgery / procedure (not endoscopic) / high bleeding risk surgery or procedure / cardiac surgery / neuraxial anaesthesia
Bleeding risk of surgery / procedure | Day -3 | Day - 2 | Day - 1 | Day of surgery / procedure | Total number of doses omitted |
|---|---|---|---|---|---|
| Low risk (endoscopic) | Continue | Continue | Continue | Omit morning dose | ONE dose |
| Low / moderate risk (not endoscopic) | Continue | Continue | Omit doses | Omit morning dose | THREE doses |
| High risk (including endoscopic / cardiac) / neuraxial anaesthesia | Continue | Omit doses | Omit doses | Omit morning dose | FIVE doses |
Bridging therapy
Bridging with therapeutic dose low molecular weight heparin (LMWH) pre-procedure is not required for patients on apixaban; see Anticoagulants – Overview.
Emergency surgery / procedure
Determine urgency of surgery / procedure.
For acute emergency procedures (which need to occur immediately)
Discontinue apixaban.
Contact Haematologist to discuss:
- use of prohaemostatic agents (see below)
- appropriateness of coagulation studies, anti-Xa levels and where available apixaban levels – note a normal PT or aPTT does not exclude an anticoagulant effect
For urgent procedures (which need to occur within hours)
- Discontinue apixaban.
- Delay procedure, if possible, for 24 hours (and at least 12 hours) after last dose of apixaban to allow plasma levels to fall.
- If the procedure cannot be delayed the risk of bleeding should be weighed against the urgency of the intervention.
- If an anticoagulant effect cannot be excluded neuraxial interventions should be avoided.
Expedited procedures (which need to occur within a few days)
Discontinue apixaban.
Follow advice under Elective surgery.
Prohaemostatic agents
The use of prohaemostatic agents might reduce the risk of peri-surgical bleeding in patients on apixaban who require emergency surgery. Discussion with a Haematologist should take place to review the measures that can be taken to control bleeding prior to and during urgent surgery.
The following agents may be considered: -
- Tranexamic acid is likely to reduce bleeding and should be considered for all patients on a DOAC prior to emergency surgery. It can be administered intravenously (IV) or orally (PO) (usual dose 1g three times a day)
- Prothrombin Complex Concentrate (PCC) can be considered, despite the lack of evidence for efficacy and safety, although routine use is not recommended. The usual view of clinicians is that PCC might improve outcomes, but this does not take into consideration the potential for adverse thrombotic events. A pragmatic approach might be to proceed with surgery, considering PCC in the event of diffuse coagulopathic bleeding. Consultant Haematologist advice must be sought before use of PCC.
- Andexanet alfa is licensed for the reversal of apixaban anticoagulation in life-threatening or uncontrolled bleeding (and has NICE approval where the life threatening, or uncontrolled bleed, is associated with the gastrointestinal tract). There is currently no evidence to support the use of andexanet alfa for the reversal of apixaban in the setting of elective or emergency surgery.
Perioperative considerations
Neuraxial (spinal / epidural) interventions or lumbar punctures
Experience is limited with the use of apixaban around neuraxial interventions and an acceptable level of residual apixaban activity to proceed with neuraxial anaesthesia is undetermined; hence there is a risk of developing an epidural or spinal haematoma that can result in long-term paralysis.
Risk factors include use of post-operative indwelling epidural catheters (vs ‘single-shot’ techniques), concomitant use of medications affecting haemostasis and traumatic or repeated epidural / spinal puncture. Before performing neuraxial intervention see Further information below.
Indwelling catheter removal advice
Continuation of apixaban should be avoided in patients requiring neuraxial interventions. Apixaban should not be administered with an indwelling catheter in situ. If anticoagulation is required, prophylactic LMWH can be considered whilst a post-operative catheter is in situ.
The next dose of apixaban should be administered at least 8 hours after neuraxial puncture or withdrawal of neuraxial catheter, this should be increased to 24 hours in the event of a traumatic puncture.
Post-operative advice
Attention to post-operative haemostasis is clinically important since too early resumption of apixaban, especially within 24 hours of surgery, may be associated with increased risk of major bleeding. Apixaban is rapidly absorbed and has a fast onset of action with peak anticoagulant activity at approximately 2 - 4 hours after the first dose.
For patients who have an indwelling catheter – see Indwelling catheter removal advice above.
Bleeding risk of procedure / surgery | Time to restart post procedure / surgery | Comments |
|---|---|---|
| Minor risk | 6 - 12 hours | With immediate and complete haemostasis |
| Low risk endoscopic | 6 - 12 hours | With immediate and complete haemostasis |
| Low / moderate risk (not endoscopic) | 24 hours | - |
High risk (including endoscopic) | 48 - 72 hours | Consider prophylactic LMWH starting 6 – 12 hours post-operatively until apixaban can be safely restarted Treatment doses may be considered necessary depending on patient’s thromboembolic risk. LMWH should be discontinued as soon as apixaban can be restarted |
Patients undergoing cardiac surgery
Some cardiac surgery, may warrant the use of post-operative unfractionated heparin (UFH). The UFH should be discontinued as soon as apixaban can be restarted. However, re-initiation of apixaban may not be appropriate following certain cardiac surgical procedures and advice should be sought from a Cardiologist / Haematologist as necessary.
Patients with reduced oral absorption post-operatively
For patients with a reduction in oral absorption post-operatively e.g post-operative ileus, gastrointestinal (GI) surgery, nausea and vomiting; consider use of prophylactic LMWH starting 6 – 12 hours post-operatively until oral treatment can be safely resumed. Treatment doses may be necessary depending on the patient’s thromboembolic risk. The LMWH should be discontinued as soon as the apixaban is restarted.
Patients undergoing bariatric surgery
Apixaban is not recommended in the immediate post-operative period following bariatric surgery and patients should be commenced on low molecular weight heparin (as per local guidelines) for a period of at least 4 weeks. Advice should be sought from a Haematologist to ensure the most appropriate anticoagulant is used following bariatric surgery.
Initiation for VTE prophylaxis following arthroplasty
Apixaban for the prevention of VTE following hip or knee arthroplasty should commence 12 - 24 hours following surgery, if haemostasis is secured.
Interactions with common anaesthetic agents
None.
Interactions with other common medicines used in the perioperative period
Non-steroidal anti-inflammatory drugs (NSAIDs)
NSAIDs are predicted to increase the risk of bleeding when given with apixaban and are ideally avoided. If there is no suitable analgesic alternative and benefit outweighs risk, cautious use may be considered for the shortest time possible; consider use of a gastroprotective agent (e.g. proton pump inhibitor).
Low molecular weight heparin (LWMH) / unfractionated heparin (UFH)
The concurrent use of apixaban with LMWH / UFH, increases the risk of bleeding and is contraindicated (unless under specific circumstances and as advised by a specialist). LMWH must be discontinued immediately upon recommencing apixaban.
Antimicrobials
Erythromycin and possibly clarithromycin, may increase the exposure to apixaban, especially with concurrent renal impairment.
Whilst single surgical prophylactic doses should not pose a problem, continued post-operative treatment may require close monitoring for excessive bleeding - consult current product literature.
Further information
Rationale for perioperative advice
The British Society for Haematology (BSH) the European Society of Cardiology (ESC) and the American College of Chest Physicians (ACCP) all support the standardised management of treatment dose DOAC in most patients undergoing elective low or high bleeding risk procedures. This is based on the PAUSE study that utilised a standardised perioperative DOAC management protocol, without routine pre-operative LWMH bridging. The authors concluded that this approach was associated with low rates of major bleeding and arterial thromboembolism. Note that only patients being treated for atrial fibrillation, on doses of 2.5mg and 5mg twice daily, with CrCl equal to or greater than 25ml/min were included in the study.
Individualisation of apixaban cessation pre-operatively may still be required, however, based on individual patient characteristics. If there is any doubt as to the pre-operative cessation of DOAC therapy in a patient, due to specific patient characteristics i.e. CrCl less than 30ml/min, weight less than 50Kg, advanced age, concomitant interacting medication; it may be prudent to discuss with a Haematologist.
It should be noted that if apixaban treatment is interrupted for more than 72 hours the likelihood of any residual apixaban level appears very low.
Neuraxial (spinal / epidural) anaesthesia or lumbar punctures
An acceptable level of residual apixaban activity to proceed with neuraxial intervention remains undetermined. Suggested time intervals for neuraxial intervention after the last apixaban administration depends on the dose (prophylactic or treatment), half-life and patient’s renal function. There should be consideration of concomitant medicines that might increase plasma apixaban levels, especially in the elderly or patients with concurrent renal impairment.
Whereas the AAGBI guidelines recommend a shorter stopping time, these guidelines are currently under review, and a broad consensus in the more recently published guidelines is that the time interval between last apixaban dose and neuraxial anaesthesia should be five half-lives for treatment doses and two half-lives for prophylactic doses. In practice, assuming creatinine clearance is equal to or greater than 30ml/min this aligns with the recommendations above for ‘high bleeding risk surgery’ which are based on the PAUSE trial where 8.2% of the apixaban cohort had neuraxial anaesthesia. Missing five doses of apixaban equates to a 60 - 67 hour gap. However, if there is any doubt to the safety of performing neuraxial anaesthesia the decision to proceed should involve a discussion between the anaesthetist and the patient, via a shared decision-making process, on the day of surgery.
Information for patients / carers
All patients (or 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 apixaban. The NUMBER of doses to omit pre-operatively should be communicated, not the number of days / hours, as this may lead to confusion about the appropriate time to stop.
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