Warfarin, DOACs and antiplatelets in adults undergoing surgery or invasive procedures (Guidelines)

TAM (Treatments and Medicines) NHS Highland
NHS Highland

Audience

  • Highland HSCP
  • Primary and Secondary Care
  • Adults only

This guideline will consider:

  • Whether and when antiplatelets and 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.
  • Please note that patients may be admitted on a combination of both antiplatelet and anticoagulant agents and it is important that advice contained within both sections is followed.
  • See also specific advice for patients who have previously undergone percutaneous coronary intervention (PCI) e.g. coronary angioplasty or stents, as it is important that an antiplatelet is continued in these patients peri-operatively.

Note: separate guideline for the management of patients on warfarin and DOACs undergoing endoscopy.

Antiplatelet agents

For ADP receptor antagonist antiplatelet agents (aspirin, clopidogrel, ticagrelor and prasugrel), the risk of adverse cardiovascular events, if antiplatelet agents are omitted, must be balanced with the risk of bleeding, if continued.

Where possible, avoid a general anaesthetic and/or surgery: 

  • Within 6 months of a stroke or transient ischaemic attack (TIA)
  • Within 4 weeks of elective PCI (stable angina)
  • Within 3 months of urgent PCI (acute coronary syndrome).
  • Consider discussion with Consultant Cardiologist if not possible to delay post PCI.
  • If surgery cannot be deferred, it should generally proceed on aspirin with temporary discontinuation of the ADP receptor antagonist.
  • Aspirin can be continued without interruption for almost all surgeries, but may need to be stopped for very high bleeding risk or confined space surgery as there is evidence that the bleeding risk may be increased.

With clopidogrel, prasugrel or ticagrelor, there is a risk of spinal or epidural haematoma if continued prior to neuroaxial anaesthesia. Low dose aspirin is considered safe for neuroaxial blockade.

Assessment of bleeding and cardiovascular/ thrombotic risks

For consideration of cardiovascular/thrombotic risk, see flowchart below. Note evidence is lacking in this area and it is important to explore risks and benefits of omitting therapy for individual patients

Flowchart 1: for the management of patients on the antiplatelet agents: clopidogrel, ticagrelor or prasugrel undergoing surgery or invasive procedures

Patient receiving antiplatelets should still receive thromboprophylaxis with low molecular weight heparin as per NHS Highland guidance.

Stopping antiplatelet agents prior to surgery

Table 1: timing of cessation of antiplatelets prior to surgery

Antiplatelet agent  Went to stop for surgery 
Aspirin Can continue (unless confined space or very high bleeding risk surgery (discuss with anaesthetist/surgeon))
Clopidogrel 7 days 
Prasugrel 7 days 
Ticagrelor 5 days 

Restarting antiplatelet agents

  • Antiplatelet agents that have been omitted should be restarted as directed by the surgeon, when bleeding risk is acceptable.
  • Where aspirin has been commenced as an alternative, this should be stopped when usual therapy is restarted. In most cases this will be the morning after the surgery, unless there are ongoing bleeding concerns or the patient may need to return to theatre.
  • For patients who have undergone carotid endarterectomy within 21 days of TIA or stroke, DAPT may be stopped post-procedure and the patient continued on long-term clopidogrel monotherapy.

Emergency surgery in patients on antiplatelet therapy

  • Where high bleeding-risk surgery is indicated and time does not allow stopping of antiplatelets for the durations recommended above, there is some evidence that platelet transfusion may improve haemostasis. Discuss with on-call haematologist, available via switchboard.
  • Consider use of pre-operative tranexamic acid.

Anticoagulant agents

  • For anticoagulant 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.
  • Bridging may not be required for procedures with a minor bleeding risk, see flowchart below for assessment of bleeding and thrombotic risks. 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 allow 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 bleeding and thrombotic risks

Flowchart 2: for the management of patients on anticoagulants undergoing surgery or invasive procedures 

Notes:

+ In the majority of patients, no bridging will be required but refer to notes below as bridging may be considered in patients at higher thromboembolic risk (e.g. additional or combination risk factors identified). See information below re PCI/stents for further advice if patient on warfarin and prescribed clopidogrel for previous PCI/stents.

* Additional risk factors in bileaflet mechanical aortic valve:

  • AF, prior stroke or TIA, hypertension, diabetes, 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 the vast majority of patients with AF do not require anticoagulation, unless moderate or severe mitral stenosis is present (very rare).

Patients admitted on warfarin: Elective surgery

Pre-operative management of patients on warfarin

  • 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 ≥ 1.5 administration of 1 to 2mg of oral vitamin K (phytomenadione 2mg / 0.2mL solution for injection, can be used orally as an off-label indication in adults) 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 MDCalc.

Peri-operative management of patients on warfarin

  • See neuroaxial tables 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 in the table below.

Table 2: Recommended enoxaparin doses for prophylaxis and treatment, including renal impairment and extremes of body weight

Enoxaparin dose

Normal renal function
[CrCl ≥ 30mls/min]

Renal impairment
[CrCl<30ml/min]

Prophylaxis:
(See also NHS Highland VTEP guidelines)

Treatment:

Prophylaxis:

Therapeutic dose:

Under 50kg: 20mg once daily

50 to 120kg: 40mg once daily

Over 120kg: 60mg once daily

Mechanical valve:
1mg/kg twice daily (maximum dose 120mg twice daily)

20mg once daily

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

All other indications: 
1.5mg/kg once daily (maximum dose 180mg once daily)

Bridging schedules

  • 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  prophylactic enoxaparin post-op be given until warfarin resumed and INR therapeutic.
    INR to be checked within 1 week of resuming warfarin therapy, to ensure it is back in therapeutic range.

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 warfarin restarted and INR therapeutic)

Day +3 onwards

Continue usual dose warfarin

Treatment dose at 18.00 unless INR therapeutic
(Continue treatment dose until warfarin restarted and INR therapeutic)

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 warfarin restarted and INR therapeutic)

Day +3 onwards

Continue usual warfarin dose

Treatment dose twice daily, until INR therapeutic \
(Continue treatment dose until warfarin restarted and INR therapeutic)

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] once daily at 08.00:
1mg/kg, maximum 120mg

Day –2

No warfarin

Prophylactic [renal dose] once daily at 08.00
All weights: 20mg

Day –1

No warfarin
Check INR
Ensure INR<1.5
See notes above

Prophylactic [renal dose] once daily 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] once daily at 18.00
All weights: 20mg
Day +1

 

Low bleeding risk:
Restart warfarin at usual dose

Low bleeding risk:
Treatment [renal dose] once daily at 18.00

High bleeding risk:
No warfarin

High bleeding risk:
Prophylactic [renal dose] once daily at 18.00
All weights: 20mg

Day +2

Usual warfarin dose

Treatment [renal dose] once daily at 18.00 if bleeding risk acceptable
(Continue treatment dose until warfarin restarted and INR therapeutic)

Day +3 onwards

Usual warfarin dose

Treatment [renal dose] once daily at 18.00 until INR therapeutic
(Continue treatment dose until warfarin restarted and 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 unit/mL (24 hourly injections). Prophylactic range: 0.1 to 0.4 unit/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 treatment dose 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 flowchart 2 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.
  • 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.
  • 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 2 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.

Patients admitted on warfarin: Emergency surgery

  • See TAM Warfarin guideline. 
  • Check INR. If INR ≥1.5: give 5mg vitamin K by slow intravenous injection. It takes 6 to 8 hours for onset of effect, and 24 hours for the full effect to be seen.
  • If there is insufficient time, reverse with Prothrombin Complex Concentrate (PCC, Beriplex®), 25 to 50 units/kg (see Table 3). Approval must be obtained from a Consultant Haematologist. Syringe pumps for Beriplex administration are situated in A&E and ICU in Raigmore (standard syringe pumps will not permit the required rate in mL/hour to be administered). For further advice on Beriplex reconstitution and administration see Anticoagulant reversal guidance (NHS Highland access required).
Table 3: 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 bridging 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 within 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.

Patients admitted on DOACs: Elective surgery

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 4. 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 MDCalc.

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 4. Bridging is not required; restart when bleeding risk is acceptable.  

Peri-operative management of patients on DOACs

* Prophylactic doses of enoxaparin should 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 very 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 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.

Patients admitted on DOACs: Emergency surgery

  • Management of Major Haemorrhage and Emergency Invasive Procedures in Patients on Direct Oral Anticoagulants (dabigatran, apixaban, edoxaban and rivaroxaban) 
  • Andexanet alfa is licensed in the UK for reversal of apixaban or rivaroxaban in life-threatening or uncontrolled bleeding. It has not been investigated when direct oral factor Xa inhibitors are administered before surgery or other invasive procedures; hence it is not currently licensed for this indication. It may be considered off-licence for edoxaban after careful discussion with consultant haematologist.
  • If an anticoagulant effect cannot be excluded, neuroaxial anaesthesia should be avoided.

Patients admitted on warfarin or DOACs with previous PCI/stents

  • See general advice for peri-operative management of patients admitted on warfarin or DOACs, as above.
  • Bridging patients post PCI (stents) with aspirin is recommended if all anticoagulation and/or antiplatelet therapy is planned to be interrupted, to reduce the risk of peri-operative myocardial infarction (provided there are no contraindications) (Graham et al, 2018). Aspirin should be commenced 7 days pre-surgery to achieve antiplatelet effect. Resume usual antiplatelet/ anticoagulant when bleeding risk acceptable, in discussion with surgeon.
  • Summary: start aspirin 75mg 7 days pre-op and stop warfarin/ DOAC as per above. 
  • Discuss with cardiology if aspirin is contra-indicated

Bleeding risk

This is not comprehensive and advice should be sought from Consultant Anaesthetist/Surgeon

Minor bleeding risk

Low bleeding risk

(bleeding infrequent or of low clinical impact)

High bleeding risk

(bleeding frequent and/or of high clinical impact)
  • Dental surgery (simple, 1 to 3 extractions, abscess incision)
  • Cataract or glaucoma surgery
  • Superficial surgery e.g. minor dermatological procedures or abscess incision
  • 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
  • Spinal or epidural anaesthesia 
  • 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

Neuroaxial block

Time required time between administration of LMWH and performance of block
  Epidural Spinal
  Normal renal function Impaired renal function
CrCl <30mL/hr		 Normal renal function Impaired renal function
CrCl <30mL/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
CrCl <30mL/hr		 Normal renal function Impaired renal function
CrCl <30mL/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
  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.

Abbreviations

Abbreviation  Meaning 
ADP  adenosine diphosphate (ADP receptor inhibitors – clopidogrel, ticagrelor, prasugrel)
AF  atrial fibrillation
APTT  activated partial thromboplastin time
CrCI  creatinine clearance
CVA  cerebrovascular accident
DOAC  direct oral anticoagulant
DVT  deep vein thrombosis
GFR  glomerular filtration rate
INR  international normalised ratio
IU  international units
LMWH  low molecular weight heparin
PCC 

prothrombin complex concentrate
PCI  percutaneous coronary intervention
PE  pulmonary embolism
PTT  partial thromboplastin time
TIA  transient ischaemic attack
VTE  venous thromboembolism

References

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Editorial Information

Last reviewed: 10/04/2024

Next review date: 30/04/2027

Author(s): Surgery.

Version: 2.2

Approved By: TAM Subgroup of the ADTC

Reviewer name(s): J Wylie, Lead Pharmacist, Surgery and Anaesthetics .

Document Id: TAM497

References

Self-management information: