Warfarin


  Issues for Surgery


Risk of venous thromboembolism (VTE) 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 warfarin 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’.

Warfarin may not need to be stopped for the following minor procedures (however it is still recommended that the international normalised ratio (INR) is checked approximately 7 days prior to the procedure to identify patients with a supra-therapeutic INR1): -

  • Dental procedures – providing INR <4 when checked up to 72 hours prior to procedure2
  • Joint injections3
  • Cataracts3
  • Pacemaker insertion3
  • Low-risk endoscopic procedures (e.g. diagnostic procedures +/- biopsy, biliary or pancreatic stenting, device-assisted enteroscopy without polypectomy) – providing INR not exceeding therapeutic range in the 7 days before procedure4.

For other operations / procedures where anticoagulation is not desirable, follow local pre-existing arrangements with hospital’s anticoagulation service. In the absence of such arrangements check INR 7 days prior to operation / procedure: -

  • If INR 1.5 - 1.9 discontinue 3 or 4 days prior to operation / procedure1
  • If INR 2.0 - 3.0 discontinue 5 days prior to operation / procedure1, 3
  • If INR > 3.0 discontinue at least 5 days operation / procedure1 – discuss with Haematologist

This should allow the INR to fall to 1.4 by day of operation / procedure5.

Check INR on admission to ensure safe to proceed with surgery / procedure3.

Bridging with Low Molecular Weight Heparin (LMWH)
Consider risk of thrombosis and risk of bleeding to assess if patient needs bridging with therapeutic dose of LMWH in the perioperative period3 (see Further Information). If bridging is needed this should either be started after 2 or 3 doses of warfarin have been missed or, if checking INR, when INR falls below 2.01.

The last dose of therapeutic LMWH should be at least 24 hours before surgery3 (see Low Molecular Weight Heparin monograph).  

Emergency Surgery / Procedures

Check INR on admission.

If INR therapeutic and surgery can be delayed for 6 to 8 hours give 5mg intravenous vitamin K (phytomenadione) to restore coagulation factors3.

If INR therapeutic and surgery cannot be delayed for sufficient time to allow reversal with vitamin K, anticoagulation can be reversed with prothrombin complex concentrate3 – discuss with Haematologist.


Perioperative Considerations

Neuraxial (Spinal / Epidural) Anaesthesia or Lumbar Punctures 

Therapeutic anticoagulation with warfarin is a relative contraindication to neuraxial anaesthesia. It is advisable not to restart warfarin until the epidural / nerve catheter has been removed5.

Post-operative Advice

Warfarin has a slow onset of action; restart on evening of operation providing adequate haemostasis and Surgeon agrees – either at usual dose1, 3 or two days of double maintenance dose followed by usual dose3.

If a patient has undergone complex surgery and there is a likelihood that the patient may need to return to theatre the Surgeon may decide to delay restarting warfarin for a few days. During this time prophylactic doses of LMWH (or therapeutic dose if high risk of thrombosis e.g. mitral valve replacement) should be considered.

If there are concerns regarding oral absorption post-operatively consider replacing warfarin with therapeutic dose LMWH as clinically appropriate.

Check INR and adjust dose accordingly.

Bridging with LMWH

Therapeutic LMWH should not be started until at least 48 hours after surgery associated with a high risk of bleeding3. Follow the advice provided by the Pre-operative Assessment Team / Haematology Team post-operatively if appropriate.

Consider prophylactic LMWH, commenced a minimum of 2 hours (4 hours for patients with indwelling catheters) post-operatively until therapeutic LMWH can be restarted.

Discontinue LMWH once INR therapeutic.


  Interaction(s) with Common Anaesthetic Agents

 

None6, 7.


  Interaction(s) with other Common Medicines used in the Perioperative Period

 

Non-Steroidal Anti-inflammatory Drugs (NSAIDs)

NSAIDs are predicted to increase the risk of bleeding events when given with warfarin; ideally concomitant use should be avoided6, 7.

Low Molecular Weight Heparin (LMWH) / Unfractionated Heparin (UFH)

LMWHs and UFH are predicted to increase the risk of bleeding events when given with warfarin6. If patient ‘bridged’ with LMWH pre-operatively this should be discontinued when INR returns to therapeutic range.

Corticosteroids

Although the evidence is limited, marked INR increases have been reported with high-dose dexamethasone, prednisolone, or methylprednisolone, however, the significance of this interaction with low doses is not known6, 7. Whilst intraoperative doses should not pose a problem, monitor INR if prolonged administration necessary.

Antimicrobials

Concomitant administration of warfarin with many antimicrobials causes an increased anticoagulant effect6, 7. Whilst single surgical prophylactic doses should not pose a problem, monitor INR if a course of antimicrobial treatment is required.

Enteral feeds

Enteral feeds containing vitamin K will reduce the anticoagulant effect of warfarin – monitor INR and adjust warfarin dose accordingly6.


  Further Information


Rationale for Advice

Warfarin has a half‐life of approximately 36 hours and as its effect wears off vitamin K‐dependent procoagulant factors need to be synthesised; therefore, providing INR is in the therapeutic range warfarin needs to be stopped 5 days before elective surgery to ensure haemostasis has returned to normal3.

Bridging with LMWH

When deciding if a patient requires bridging the risk of thrombosis must be weighed against the risk of bleeding - see  ‘Anticoagulants (Oral) – A General Overview’. In patients with atrial fibrillation (AF) a randomised controlled trial found that not bridging was non-inferior to perioperative bridging with LMWH for the prevention of arterial thromboembolism and reduced the risk of major bleeding. Therefore, the British Committee for Standards in Haematology only recommend bridging for AF patients at high risk of thrombosis3.

Consider bridging with treatment dose LMWH for the following indications3: -

  • Patients with VTE within last 3 months
  • Patients with previous VTE whilst on therapeutic anticoagulation who now have target INR of 3.5
  • Patients with a CVA / TIA in last 3 months
  • Patients with a previous CVA / TIA and 3 of the following:
    • Congestive cardiac failure
    • Hypertension (either BP >140/90mmHg or on antihypertensive treatment)
    • Age >75 years
    • Diabetes mellitus
  • Metallic heart valve (except bileaflet aortic valve patients with no other risk factors e.g. previous CVA / TIA, atrial fibrillation or reduced left ventricular ejection fraction)


  References


  1. Doherty J, Gluckman T, Hucker W et al. 2017 ACC Expert Consensus Decision Pathway for Periprocedural Management of Anticoagulation in Patients with Nonvalvular Atrial Fibrillation – A Report of the American College of Cardiology Clinical Expert Consensus Document Task Force. Journal of the American College of Cardiology. 2017; 69(7):871-898
  2. Scottish Dental Clinical Effectiveness Programme (SDCEP). Management of Dental Patients Taking Anticoagulants or Antiplatelet Drugs: Dental Clinical Guidance Date prepared August 2015. Available at http://www.sdcep.org.uk/published-guidance/anticoagulants-and-antiplatelets [Accessed on 9th September 2019]
  3. Keeling D, Campbell Tait R, Watson H on behalf of the British Committee for Standards in Haematology. Peri-operative management of anticoagulation and antiplatelet therapy. British Journal of Haematology. 2016; 175:602-612
  4. Veitch A, Vanbiervliet G, Gershlick A et al. Endoscopy in patients on antiplatelet or anticoagulant therapy, including direct oral anticoagulants: British Society of Gastroenterology (BSG) and European Society of Gastrointestinal Endoscopy (ESGE) guidelines. Gut. 2016; 65:374-389
  5. Association of Anaesthetists of Great Britain and Ireland, Obstetric Anaesthetists’ Association and Regional Anaesthesia UK.    Regional anaesthesia and patients with abnormalities of coagulation.  Anaesthesia 2013; 68: pages 966-72.
  6. Joint Formulary Committee. British National Formulary (online) London: BMJ Group and Pharmaceutical Press. http://www.medicinescomplete.com [Accessed on 9th September 2019]
  7. Baxter K, Preston CL (eds), Stockley’s Drug Interactions (online) London: Pharmaceutical Press. http://www.medicinescomplete.com [Accessed on 9th September 2019]