Warfarin and Direct Oral Anticoagulants (DOACs) in Adult Patients Undergoing Surgery or Invasive Procedures

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This guideline will consider whether and when anticoagulants should be stopped before elective surgery and invasive procedures, when agents can be restarted and how to manage patients on these agents who require emergency surgery.  Note that a separate guideline is in place for the management of patients on warfarin and DOACs undergoing endoscopy.

For agents with a slow offset and onset of action (warfarin), bridging therapy with an alternative agent (treatment dose low molecular weight heparin [LMWH]) can be considered in patients at high risk of thrombosis.  Thromboprophylaxis with low dose LMWH is not regarded as ‘bridging’.  Bridging therapy is not required pre-surgery or procedure for direct oral anticoagulants (DOACs) due to predictable pharmacokinetics which allows for properly-timed cessation prior to surgery, but should be considered post-surgery or procedure if unable to resume their usual DOAC e.g. oral route is unavailable.

Assessment of thrombosis and bleeding risks

The decision about whether to continue or interrupt anticoagulation depends on the risk of bleeding associated with the planned procedure, and the patient’s underlying thrombotic risk.  See Figure 1.

* Additional risk factors in bileaflet mechanical aortic valve: AF, prior stroke or TIA, hypertension, diabetes mellitus, heart failure or left ventricular dysfunction, age >75 years. Consider bridging in these patients depending on the bleeding risk; refer to consultant anaesthetist/surgeon.

**Low risk thrombophilia: Heterozygous Factor V Leiden or prothrombin gene mutation.

**** High risk thrombophilia: Protein C or S deficiency, antithrombin deficiency, antiphospholipid syndrome, homozygous Factor V Leiden or homozygous prothrombin gene mutation, or combinations.

Atrial Fibrillation (AF)

Clinical trials have shown that bridging for AF does not reduce the risk of ischaemic/embolic events and increases bleeding.  It is therefore recommended that AF is not bridged peri-operatively. 

Pre-operative management of patients on warfarin

  • If patients present to pre-assessment on warfarin for AF (without mitral stenosis), they should be referred back to their GP for consideration of switching to a DOAC pre-operatively, if there is sufficient time before surgery. DOACs are associated with a reduced bleeding risk and a briefer interruption of therapy peri-operatively will be required.
  • Warfarin has a half-life of 36 hours and should be stopped 5 days pre-operatively.
  • The INR should be checked on the day before surgery. If INR ≥5 administration of 1 to 2mg of oral vitamin K (Konakion MM Paediatric®) should be considered, bearing in mind it may take longer for the INR to return to therapeutic range because of the ongoing effects of Vitamin K.  Inform Consultant Anaesthetist and Surgeon.
  • Patients with impaired renal function should ideally have their creatinine clearance calculated using the Cockcroft-Gault equation and using ideal body weight (see online calculator).

Peri-operative management of patients on warfarin

  • Refer to Appendix 2 for guidance on management of patients requiring neuroaxial anaesthesia, to minimise the risk of spinal haematoma associated with anticoagulation.
  • The recommended doses of enoxaparin to be used for prophylaxis and bridging therapy (i.e. therapeutic dose) are outlined below in Table 1.

Table 1: Recommended enoxaparin doses for prophylaxis and treatment, including renal impairment and extremes of body weight

 

Normal renal function [CrCl ≥ 30mls/min]

Renal impairment [CrCl<30ml/min]

Enoxaparin

Prophylaxis

Under 50kg: 20mg once daily

50 to 120kg: 40mg once daily

Over 120kg:

60mg once daily

Treatment dose, mechanical valve:

1mg/kg twice daily (maximum dose 120mg twice daily)

Prophylaxis:

20mg once daily

Therapeutic dose:

1mg/kg once daily (all indications) (maximum dose 120mg once daily)

  • There are three different schedules for stopping warfarin and bridging with enoxaparin peri-operatively, depending on indication for warfarin (thrombosis risk) and renal function. Please refer to the appropriate schedule below.
  • For patients on warfarin not requiring bridging, warfarin should be stopped 5 days pre-op and be given prophylactic enoxaparin post-op until warfarin resumed and INR therapeutic. INR should be checked within 1 week of resuming warfarin therapy, to ensure it is back in therapeutic range.

Bridging Schedule 1: Any indication excluding mechanical heart valves, normal renal function

Bridging Schedule 1: Adult patients on warfarin requiring bridging for any indication excluding mechanical heart valves with normal renal function [CrCl≥30ml/min]

 

Warfarin

LMWH (enoxaparin)

Day – 5

No warfarin

No LMWH

Day – 4

No warfarin

No LMWH

Day – 3

No warfarin

Treatment dose at 18.00

(1.5mg/kg to maximum of 180mg)

Day – 2

No warfarin

Treatment dose at 18.00

Day – 1

No warfarin

Check INR

Ensure INR<1.5. See notes above

Prophylactic dose at 18.00

Under 50kg: 20mg

50 to 120kg: 40mg

Over 120kg: 60mg

Day of operation (day 0)

No warfarin

Prophylactic dose at 18.00 unless otherwise directed

Day + 1

Low bleeding risk

Restart warfarin at usual dose

Low bleeding risk

Treatment dose at 18.00  

High bleeding risk

No warfarin

High bleeding risk

Prophylactic dose at 18.00

Day + 2

Usual warfarin dose

Treatment dose at 18.00 for all patients if bleeding risk acceptable (continue treatment dose until INR therapeutic)

Day +3 onwards

Continue usual dose warfarin

Treatment dose at 18.00 unless INR therapeutic (continue treatment dose until INR therapeutic)

Bridging Schedule 2: Mechanical heart valves, normal renal function

Bridging Schedule 2: Adult patients on warfarin for a mechanical heart valve or bileaflet mechanical aortic valve with additional risk factors with normal renal function [CrCl≥30ml/min]

 

Warfarin

LMWH (enoxaparin)

Day – 5

No warfarin

No LMWH

Day – 4

No warfarin

No LMWH

Day – 3

No warfarin

Treatment dose twice daily

1mg/kg, max 120mg twice daily

Day – 2

No warfarin

Treatment dose twice daily

Day – 1

No warfarin

Check INR

Ensure INR<1.5. See notes above

Prophylactic dose at 18:00

Under 50kg: 20mg

50 to 120kg: 40mg

Over 120kg: 60mg

Day of operation (day 0)

No warfarin

Prophylactic dose at 18.00

Day + 1

Low bleeding risk

Restart warfarin at usual dose

Low bleeding risk

Treatment dose twice daily

High bleeding risk

No warfarin

High bleeding risk

Prophylactic dose at 18.00

Day + 2

Usual warfarin dose

Treatment dose twice daily if bleeding risk acceptable (continue treatment dose until INR therapeutic)

Day +3 onwards

Continue usual warfarin dose

Treatment dose twice daily, until INR therapeutic (continue treatment dose until INR therapeutic)

Bridging Schedule 3: Impaired renal function, all indications

Bridging Schedule 3: Adult patients on warfarin for any indication with impaired renal function [CrCl<30ml/min*]

 

Warfarin

LMWH

Day – 5

No warfarin

No LMWH

Day – 4

No warfarin

No LMWH

Day – 3

No warfarin

 

Treatment [renal dose] at 08.00

1mg/kg, maximum 120mg

Day – 2

No warfarin

Prophylactic [renal dose] at 08.00

All weights: 20mg

Day – 1

No warfarin

Check INR

Ensure INR<1.5. See notes above

Prophylactic [renal dose] at 08.00

Omit dose if cannot be given at 08.00

All weights: 20mg

Day of operation (day 0)

No warfarin

Prophylactic [renal dose] at 18.00

All weights: 20mg

Day + 1

Low bleeding risk

Restart warfarin at usual dose

Low bleeding risk

Treatment [renal dose] at 18.00

High bleeding risk

No warfarin

High bleeding risk

Prophylactic [renal dose] at 18.00

All weights: 20mg

Day + 2

Usual warfarin dose

Treatment [renal dose] at 18.00 if bleeding risk acceptable (continue treatment dose until INR therapeutic)

Day +3 onwards

Usual warfarin dose

Treatment [renal dose] at 18.00 until INR therapeutic (continue treatment dose until INR therapeutic)

*If creatinine clearance is less than 15ml/min please discuss with haematology or renal consultant.

Anti-factor Xa levels should be monitored in patients with renal impairment who receive LMWH for 3 or more days.  Use a citrate (green) tube and take samples 4 hours post injection.

Therapeutic range: 1.0 to 2.0 IU/ml (24 hourly injections).  Prophylactic range: 0.1 to 0.4 IU/ml.

Post-operative management of patients on warfarin

  • Resume normal warfarin and treatment enoxaparin dose post-operatively according to the schedules above, in general:
    • Low bleeding risk - wait 24 hours
    • High bleeding risk and after major surgery - wait at least 48 hours
  • In some circumstances, e.g. where it is likely that a patient may return to the operating theatre, it may be necessary to withhold restarting enoxaparin and usual warfarin for longer than outlined in the schedule. Cardiology must be informed if the patient has a mechanical valve so that a heparin infusion can be considered. Haematology must be consulted if the patient is considered high risk as per Figure 1 above (VTE within 3 months, prior recurrent VTE with target INR of 3.5 or high risk thrombophilia).
  • Treatment enoxaparin must be continued as per schedules above until the INR is therapeutic for patients who require bridging therapy. In patients who remain nil-by-mouth for a prolonged period post-operatively, it will be necessary to continue treatment enoxaparin until oral anticoagulation can be re-established.
  • In patients with AF and no additional risk factors who were not switched to a DOAC pre-operatively, consideration should be made to switch to a DOAC post-operatively to reduce long-term bleeding risk and achieve prompt therapeutic anticoagulation sooner. Patients discharged on warfarin for AF should be referred back to their GP for this to be reviewed in the community, if not reviewed in hospital.
  • For patients undergoing surgery with a very high bleeding risk, a heparin infusion can be considered, however managing heparin infusions is labour-intensive and requires frequent blood tests and a continuous intravenous infusion. Ensure nurses are familiar with heparin infusions and staffing levels are adequate before prescribing.  A high dependency area may be more suitable for nursing patients requiring a heparin infusion peri-operatively. Heparin charts are available on wards.
  • In patients who were not bridged but where usual warfarin cannot be resumed within 48 to 72 hours post-operatively (e.g. prolonged ileus), treatment dose enoxaparin should be considered (see Table 1 for dosing) in patients with a high thromboembolic risk, if bleeding risk acceptable. However the majority of warfarin patients with high thromboembolic risk should have received peri-operative bridging therapy.

Peri-operative management of patients on warfarin undergoing emergency surgery

Table 2: Beriplex® (PCC) dosing                                     

Initial INR

2.0 to 3.9

4.0 to 6.0

>6.0

Approximate intravenous dose (units/kg)

25

35

50

  • Recheck INR and give further Beriplex (PCC) if needed. The maximum single dose is 5000 units.
  • Correction of the INR persists for approximately 6 to 8 hours with PCC. Simultaneous administration of vitamin K with PCC should mean that repeated administration is not required.
  • Post-operatively, patients can be managed in the same way as elective patients (see tables above), bearing in mind it may take longer for the INR to return to therapeutic range because of the ongoing effects of Vitamin K
  • If patients with a metal valve do not commence treatment dose LMWH by 48 hours post-op due to high bleeding risk, surgical complications etc., this must be discussed with a cardiologist as a heparin infusion may be required.

Management of patients admitted on Direct Oral Anticoagulants (DOACs)

Pre-operative management of patients on DOACs
  • DOACs have an almost immediate onset of action (peak levels are achieved within 2 to 4 hours of a dose) and they do not usually require any routine monitoring.
  • The last dose of DOAC should be timed to achieve normal coagulation status by the time of surgery. See table 3. The timing of the last dose depends on the patient’s renal function, the half-life of the DOAC and the risk of bleeding associated with the surgery or procedure. DOACs do not require pre-operative bridging with treatment doses of LMWH.
  • Patients with impaired renal function should ideally have their creatinine clearance calculated using the Cockcroft-Gault equation and using ideal body weight (see online calculator).

Dabigatran

  • Dabigatran is a direct thrombin inhibitor with a half-life of 13 hours in normal renal function.
  • A normal APTT excludes excess levels of dabigatran but there may still be anticoagulant activity

Rivaroxaban, Apixaban and Edoxaban

  • Rivaroxaban, apixaban and edoxaban are direct Factor Xa inhibitors.
  • In normal renal function, the rivaroxaban half-life is 5 to 9 hours; apixaban is 12 hours and edoxaban is 10 to 14 hours.
  • Anti-Xa assay specific to these drugs is unavailable in NHS Highland at present.
  • A normal coagulation screen does not exclude the presence of significant concentrations of the circulating drug.

Low-dose rivaroxaban

  • Rivaroxaban 2.5mg in combination with aspirin is licensed for the prophylaxis of atherothrombotic events in patients with coronary artery disease or symptomatic peripheral artery disease at high risk of ischaemic events.
  • Pre-operative cessation of low-dose rivaroxaban has not been studied.  Stop low-dose rivaroxaban pre-surgery as per table 3.  Bridging is not required; restart when bleeding risk is acceptable. 
Management of DOACs peri-operatively

* Prophylactic doses of enoxaparin can be considered in the post-operative period until normal DOAC is resumed.  Should surgery be delayed for any reason, commence prophylactic enoxaparin from the evening of the planned day of surgery until surgery has taken place and DOAC is resumed.  If surgery to be rescheduled for a later date, resume DOAC and follow advice above prior to rescheduled procedure.

+ For patients undergoing a minor procedure with a low bleeding risk (see Appendix 1), the DOAC may be able to be restarted 6 to 12 hours after the procedure.  Seek physician’s advice.

Post-operative management of patients admitted on DOACs
  • For patients undergoing surgery with a high bleeding risk or where even minimal blood loss is unacceptable, the DOAC should be restarted 48 hours post-operatively or when the bleeding risk is acceptable.
  • If DOACs cannot be resumed within 48 to 72 hours post-operatively (e.g. prolonged ileus), treatment dose enoxaparin should be considered (see table 1 for dosing) in patients with a high thromboembolic risk, if bleeding risk acceptable.
Peri-operative management of patients on DOACs undergoing emergency surgery

Appendix 1 - Risk of bleeding (this is not comprehensive and advice should be sought from Consultant Anaesthetist/Surgeon)

Minor bleeding risk

Dental surgery (simple 1-3 extractions, abscess incision)

Cataract or glaucoma surgery

Superficial surgery e.g. minor dermatological procedures or abscess incision

Low bleeding risk (bleeding infrequent or of low clinical impact)

Prostate or bladder biopsy

Pacemaker or ICD insertion

Biliary or pancreatic stenting

Bronchoscopy +/- biopsy

Arthroscopy

Shoulder/foot/hand surgery

Coronary angiography

Laparoscopic cholecystectomy

Abdominal hernia

Bone marrow biopsy

High bleeding risk (bleeding frequent and/or of high clinical impact)

Spinal or epidural anaesthesia (see Appendix 1)

Thoracic surgery

Abdominal surgery

Major orthopaedic surgery

Liver biopsy

Transurethral resection of prostate, bladder or tumour ablation

Kidney biopsy

Complex ophthalmologic operations

Reconstructive plastic surgery

Urologic surgery

Surgery in highly vascularised organs

Total abdominal hysterectomy

Peg tube insertion 

Appendix 2 - Management of patients requiring neuroaxial block

Required time between administration of LMWH and performance of block

 

Epidural

Spinal

Normal renal function

Impaired renal function

[Creatinine clearance < 30mls/hr]

Normal renal function

Impaired renal function

[Creatinine clearance < 30mls/hr]

Prophylactic LMWH (enoxaparin)

 

Wait 12 hours

Wait 24 hours

Wait 12 hours

Wait 24 hours

Treatment LMWH (enoxaparin)

Not recommended but if used, wait 24 hours

 

Not recommended

Wait 24 hours

Wait 48 hours

Time between performance of block/removal of catheter and next dose of LMWH

 

Epidural

Spinal

Normal renal function

Impaired renal function

[Creatinine clearance < 30mls/hr]

Normal renal function

Impaired renal function

[Creatinine clearance < 30mls/hr]

Prophylactic LMWH (enoxaparin)

4 hours

4 hours

4 hours

4 hours

Treatment LMWH (enoxaparin)

Wait 4 hours after indwelling catheter removed and at least 24 hours after needle/catheter placement (whichever is greater) – i.e. if catheter removed early for any reason, ensure at least 24 hours after insertion before administration of treatment dose LMWH.

4 hours

4 hours

Time between administration of DOAC and performance of block/catheter insertion; and between removal of catheter and next dose of DOAC

DOAC

CrCl (ml/min)

Time between last dose of DOAC and catheter insertion

Minimum time to next dose of DOAC following catheter removal

Apixaban

N/A

24 to 48 hours

 

 

6 hours (24 hours if traumatic puncture)

Dabigatran

>80

48 hours

50 to 79

72 hours

30 to 49

96 hours

Edoxaban or rivaroxaban

≥30

18 hours

<30

48 hours

It is advisable to avoid epidural analgesia in patients requiring bridging anticoagulation, particularly in patients with renal impairment.

Glossary

AF – atrial fibrillation

APTT – activated partial thromboplastin time

CrCl – creatinine clearance

CVA – cerebrovascular accident

DOAC – direct oral anticoagulant

DVT – deep vein thrombosis

GFR – glomerular filtration rate

INR – international normalised ratio

IU – international units

PCC – prothrombin complex concentrate

PE – pulmonary embolism

PTT – partial thromboplastin time

TIA – transient ischaemic attack

VTE – venous thromboembolism

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Last reviewed: 30 April 2022

Next review: 30 April 2025

Author(s): Lead Pharmacist, Surgery and Anaesthetics

Approved By: TAM Subgroup of ADTC

Reviewer Name(s): Lead Pharmacist, Surgery and Anaesthetics

Document Id: TAM497