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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.

For cerebral arterial disease (CAD) or peripheral arterial disease (PAD) - risk of atherothrombotic event 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, dose, and frequency of administration

Confirm the dose, timing and frequency of administration with patient / carer (this will affect pre-operative cessation advice).

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 rivaroxaban 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.

Rivaroxaban 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 rivaroxaban interruption (where possible time the procedure for 12 hours after the last dose).

Low bleeding risk endoscopic procedure

Time of administration	Day -2	Day -1	Day of procedure	Total number of doses omitted
Once daily in the MORNING	Continue	Continue	Omit morning dose	ONE dose
Once daily in the EVENING	Contniue	Dose taken by 8pm	N/A	None
TWICE daily*	Continue	Evening dose taken by 8pm	Omit morning dose	ONE dose

* 2.5mg twice daily for PAD / CAD

Low / moderate bleeding risk surgery / procedure (not endoscopic)

Time of administration	Day -2	Day -1	Day of surgery / procedure	Total number of doses omitted
Once daily in the MORNING	Continue	Omit dose	Omit dose	TWO doses
Once daily in the EVENING	Continue	Omit dose	N/A	ONE dose
TWICE daily*	Continue	Continue	Omit dose	ONE dose

* 2.5mg twice daily for PAD / CAD

High bleeding risk surgery (including cardiac surgery) / procedure (including endoscopic procedure) / patient to receive neuraxial anaesthesia

Time of administration	Day -3	Day -2	Day -1	Day of surgery / procedure	Total number of doses omitted
Once daily in the MORNING	Continue	Omit dose	Omit dose	Omit dose	THREE doses
Once daily in the EVENING	Continue	Omit dose	Omit dose	N/A	TWO doses
TWICE daily*	Continue	Continue	Omit evening dose	Omit morning dose	TWO doses

* 2.5mg twice daily for PAD / CAD

Bridging therapy

Bridging with therapeutic dose low molecular weight heparin (LMWH) pre-procedure is not required for patients on rivaroxaban; see Anticoagulants – Overview.

Emergency surgery / procedure

Determine dose of rivaroxaban (risk of bleeding is likely to be lower with 2.5mg twice daily dosing used for PAD / CAD) and urgency of surgery / procedure.

For acute emergency procedures (which need to occur immediately)

Discontinue rivaroxaban.

Contact Haematologist to discuss:

• use of prohaemostatic agents (see below) – note there is no specific reversal agent for rivaroxaban
• appropriateness of coagulation studies, anti-Xa levels and, where available, rivaroxaban levels – note a normal PT or aPTT does not exclude an anticoagulant effect

For urgent procedures (which need to occur within hours)

Discontinue rivaroxaban.

Delay procedure, if possible, for 24 hours (and at least 12 hours) after last dose of rivaroxaban 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 rivaroxaban.

Follow advice under elective surgery.

Prohaemostatic agents

The use of prohaemostatic agents might reduce the risk of peri-surgical bleeding in patients on rivaroxaban 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 rivaroxaban 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 rivaroxaban in the setting of elective or emergency surgery.

Perioperative considerations

Neuraxial (spinal / epidural) interventions or lumbar punctures

Experience is limited with the use of rivaroxaban around neuraxial interventions and an acceptable level of residual rivaroxaban 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 rivaroxaban should be avoided in patients requiring neuraxial interventions. Rivaroxaban 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 rivaroxaban 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 rivaroxaban, especially within 24 hours of surgery, may be associated with increased risk of major bleeding. Rivaroxaban is rapidly absorbed and has a fast onset of action with peak anticoagulant activity at approximately 2 – 4 hours after the first dose. Rivaroxaban should be administered with food, to ensure efficacy, so should only be restarted once the patient is able to tolerate oral intake.

For patients who have an indwelling catheter – see Indwelling catheter removal advice above.

Bleeding risk of surgery / procedure	Time to restart post surgery / procedure	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 rivaroxaban can be safely restarted Treatment doses may be considered necessary depending on patient's thromboembolic risk. LMWH should be discontinued as soon as rivaroxaban 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 rivaroxaban can be restarted. However, reinitiation of rivaroxaban 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 rivaroxaban is restarted.

Patients undergoing bariatric surgery

Rivaroxaban 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. The bioavailability of rivaroxaban is likely to be reduced following bariatric surgery, particularly procedures that resect or bypass the stomach. In addition, therapeutic doses of rivaroxaban (15mg and 20mg tablets) should be taken with food to maximise oral bioavailability. Hence, it may not be the preferred anticoagulant of choice. Advice should be sought from a Haematologist.

Initiation for VTE prophylaxis following arthroplasty

Rivaroxaban for the prevention of VTE following hip or knee arthroplasty should commence 6 - 10 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 rivaroxaban 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 rivaroxaban 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 rivaroxaban.

Antimicrobials

Clarithromycin and possibly erythromycin, may increase the exposure to rivaroxaban, especially with concurrent renal impairment. This is not thought to be clinically significant, however bleeding has been reported.

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 15mg and 20mg per day, with CrCl equal to or greater than 30ml/min were included in the study.

Individualisation of rivaroxaban 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 rivaroxaban treatment is interrupted for more than 72 hours the likelihood of any residual rivaroxaban level appears very low.

Neuraxial (spinal / epidural) anaesthesia or lumbar punctures

An acceptable level of residual rivaroxaban activity to proceed with neuraxial intervention remains undetermined. Suggested time intervals for neuraxial intervention after the last rivaroxaban 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 rivaroxaban 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 rivaroxaban 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 6.5% of the rivaroxaban cohort had neuraxial anaesthesia. Missing three morning doses of rivaroxaban equates to a 72 - 76 hour gap and missing two evening doses 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 rivaroxaban. 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.

References

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