Guidelines for the Perioperative Management of Warfarin in Patients Undergoing Elective Procedures

1. Summary of recommendations
2. Aims
3. Objectives
4. Scope
5. Exclusions
6. Background
7. Assessing the risk of bleeding
8. Assessing the risk of thromboembolism
   Atrial fibrillation
   Mechanical Heart Valves
   Venous thromboembolism
   Thrombophilia
9. Stopping warfarin before surgery
10. Starting bridging anticoagulation before surgery if indicated
    Low molecular weight heparin
    Unfractionated heparin
11. Monitoring for heparin induced thrombocytopenia
12. Assessing the risk of post operative bleeding
13. Restarting bridging anticoagulation after surgery
    Patients with spinal/epidural catheters
14. Restarting warfarin after surgery
15. Discharging patients
16. Cancelled surgery >> In light of a cancelled procedure please go straight to this section
    New date of surgery within two weeks
    New date of surgery not confirmed or in more than two weeks
17. Audit and Monitoring Compliance
18. Provenance
19. References

Summary of recommendations

*If patients are undergoing major surgery with a high bleeding risk or likely to have a spinal or epidural anesthesia it has been suggested the dose of therapeutic low molecular weight heparin (LMWH) may be halved the day before surgery. For patients on twice daily dosing of enoxaparin, the last dose should be administered at 08:00 on the morning before the day of surgery.

** CHA2DS2-VASc score includes more common stroke risk factors and superseded the CHADS2 score but only the CHADS2 has been validated for risk assessment within the peri-operative period and so is used for guiding the need for bridging anticoagulation therapy

*** Continue prophylactic dose LMWH whilst INR is sub-therapeutic.

**** Patients who have had a procedure with a very high risk of bleeding or bleeding complications during surgery may need to postpone their warfarin initiation until the surgeon is confident the bleeding risk has minimised.

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Aims

This guideline discusses the perioperative management of patients undergoing elective surgery who are taking warfarin and the role of ‘bridging’ therapy with heparin.

Objectives

To provide evidence based recommendations for the management of perioperative anticoagulation.

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Scope

This guideline applies to adult patients requiring interruption to warfarin or other vitamin K antagonists prior to elective procedures.

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Exclusions

• Emergency surgery
  Emergency surgery in anticoagulated patients should be discussed urgently with haematology (coagulation registrar through switchboard).

• Minor surgery that does not require interruption of anticoagulation
  Some minor surgical procedures with a very low bleeding risk (e.g. minor dental, ophthalmological and dermatological procedures) may be performed whilst maintaining anticoagulation at the discretion of the Consultant. An INR safe to proceed with should be checked either the day before or on the day of surgery to ensure that the INR is not supra-therapeutic.

• Endoscopy
  See the Management of Oral Anticoagulant and Antiplatelet Drugs in Patients Attending for Elective Endoscopy for patients undergoing endoscopic procedures.

• Allergy to heparin or heparin products
  Patients who require bridging with heparin but have a documented allergy to it or have had a previous diagnosis of heparin induced thrombocytopenia should be discussed with haematology (coagulation registrar via switchboard).

• New or direct oral anticoagulants
  See the Guidelines for the Peri-operative Management of New Oral Anticoagulants for Patients Undergoing Elective Procedures.

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Background

Oral anticoagulant therapy with warfarin is commonly prescribed for

• Treatment of deep venous thrombosis and pulmonary embolism and prevention of recurrence
• Reduction of stroke and systemic embolism in patients with atrial fibrillation, transient ischaemic attacks (TIAs) and/or mechanical heart valves
• Other indications include arterial embolism, anti-phospholipid syndrome, renal, hepatic and other venous thromboses

In the elective perioperative period, the risk and the consequences of thrombosis must be weighed against the risk and consequences of excess bleeding. The evidence on which to base recommendations is not robust and there is a distinct lack of high quality randomised controlled trials. All patients must be considered on an individual basis with an assessment of individual patient and surgery related factors using this guideline to aid decision making.

The options for the management include:

• Continue warfarin therapy with INR monitoring
• Temporarily withhold warfarin therapy for a period pre- and post-operatively
• Temporarily withhold warfarin and provide a ‘heparin bridge’ with either inpatient administration of intravenous unfractionated heparin (IV UFH) or LMWH at a prophylactic or therapeutic dose.

Patients should have a clear perioperative anticoagulation plan prior to elective surgery. The indication for anticoagulant therapy and the nature of the elective procedure should be included in the risk assessment of thrombosis and bleeding. The decision should be documented on surgical booking form and/or the clinic letter as appropriate. The reversal of anticoagulation with vitamin K should be avoided where possible.

Patients should be made aware of the risks of stopping anticoagulation for a procedure and best efforts made to ensure they understand these risks.

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Assessing the risk of bleeding

The administration of anticoagulant therapy in the perioperative period should consider the combined risk and/or consequences of bleeding associated with the surgery or procedure and the administration of anticoagulation in the individual patient circumstances. Anticoagulants should be administered with extreme caution in patients undergoing high bleeding risk procedures and may need to be curtailed all together.

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Assessing the risk of systemic embolism

In patients at high risk of stroke or VTE the need to prevent a thromboembolic event will dominate perioperative management of anticoagulation. The potential consequences of thromboembolic events, which may be fatal, will in most cases outweigh the potential clinical consequences of bleeding and will justify the need for bridging anticoagulation. Conversely, in patients classified at a low risk of thromboembolism bridging therapy may not be required and standard prophylaxis may be used when warfarin is interrupted.

The risk of thromboembolism depends on the following factors:

• Indication for oral anticoagulation
• Individual patient factors and clinical history
• Duration anticoagulation withheld (for review if procedure cancelled)

Atrial fibrillation (AF)
In patients with atrial fibrillation, the CHADS2 [1] and CHA2DS2-VASc [2] score can be used in clinical practice to assess the risk of systemic embolism. The CHA2DS2-VASc score includes more common stroke risk factors and superseded the CHADS2 score but only the CHADS2 has been validated for risk assessment within the peri-operative period and is used for guiding the need for bridging anticoagulation therapy.

The CHADS₂ score can stratify patients with atrial fibrillation into a low (CHADS₂ score = 0 - 2), moderate (CHADS₂ score = 2 - 4) or high risk (CHADS₂ score 5 - 6) category for embolic events. However, bridging with LMWH in patients within the low to moderate risk category has been shown to significantly increase the risk of bleeding and not reduce the risk of stroke, systemic embolism or TIAs [3]. Patients with AF at high risk of embolism are those with a CHADS₂ score ≥5, rheumatic heart disease, a recent stroke within 3 months or previous multiple strokes should be bridged with therapeutic dose LMWH. Valvular AF (mitral stenosis) should also be bridged especially if higher INR target.

Mechanical Heart Valves

Mechanical heart valves increase the risk of systemic embolism (e.g. stroke, valvular or intracardiac thrombosis). The thrombogenicity of mechanical valves depends on the position, the type of valve and other patient related risk factors. Valves in the aortic position generally carry a lower risk of thrombosis and embolisation than valves in the mitral position. On-X valves should be bridged as per other mechanical heart valves. Bileaflet aortic valves generally carry a lower risk of thromboembolism and do not require bridging if there are no other concurrent risk factors. Any mitral valve prosthesis, caged ball or tilting disk aortic valve prosthesis carry a high risk of thromboembolism. The type of heart valve can be confirmed by the patient who may carry a card detailing this information or by reviewing medical notes and clinic letters. If it is unclear what type of valve a patient has their cardiologist or cardiac surgeon should be contacted to confirm. Patient related risk factors that increase the risk of thromboembolism alongside mechanical heart valves include AF, LVEF <30%, mitral stenosis of any degree and previous thromboembolism.

Venous thromboembolism (VTE)and thromboses at unusual sites

Following a VTE, interruption of anticoagulation during the first 3 months or 6 months alongside active cancer is associated with a very high rate of recurrence. If possible, elective surgery should be delayed until after this high risk time period to reduce the risk of further thromboembolism. Within this time period consider therapeutic dose LMWH for patients undergoing urgent elective procedures. Under very select circumstances (for example, when urgent surgery is required within four weeks of an episode of VTE) an IVC filter may be considered and any patient requiring surgery within 3 months of their VTE. A specialist opinion from a vascular radiologist and a haematologist should be sought in advance in such cases. When this initial 3 to 6 month acute treatment phase is completed, there is a lower risk of VTE reoccurrence and the treatment indication for those who remain anti-coagulated after this time is secondary prevention. In these cases, give post-operative prophylactic dose LMWH whilst INR is sub-therapeutic. Please note cerebral venous sinus thrombosis also falls within this section.

Patients who experience VTE whilst on therapeutic anticoagulation usually have an INR target >2.5 and are also high risk for thromboembolism. Consider bridging with therapeutic dose LMWH whilst warfarin withheld peri-operatively.

Arterial Thrombosis
Please discuss whether bridging is needed with the patient’s cardiology or vascular consultant

Thrombophilia
The following conditions are associated with a high risk of VTE:

• Antiphospholipid Syndrome
• Antithrombin III Deficiency (heparin ineffective in these patients, please involve haematology in plan)
• Protein C Deficiency
• Protein S Deficiency Combined thrombophilias or homozygous Factor V Leiden

Antiphospholipid Syndrome and Protein C and S Deficiencies should always be bridged.

For the other conditions listed or if any uncertainties please ensure to have contacted the coagulation registrar.

Summary of recommendations [4, 5]

*If patients are undergoing major surgery with a high bleeding risk or likely to have a spinal or epidural anesthesia it has been suggested the dose of therapeutic low molecular weight heparin (LMWH) may be halved the day before surgery. For patients on twice daily dosing of enoxaparin, the last dose should be administered at 08:00 on the morning before the day of surgery.

** CHA₂DS₂-VASc score includes more common stroke risk factors and superseded the CHADS₂ score but only the CHADS₂ has been validated for risk assessment within the peri-operative period and so is used for guiding the need for bridging anticoagulation therapy

*** Continue prophylactic dose LMWH whilst INR is sub-therapeutic.

**** Patients who have had a procedure with a very high risk of bleeding or bleeding complications during surgery may need to postpone their warfarin initiation until the surgeon is confident the bleeding risk has minimised.

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Stopping warfarin before surgery

Warfarin should be stopped for 5 days prior to an elective surgical procedure to allow the INR to reduce [4, 5, 6].

The INR should be checked the day before or on the morning of surgery to confirm it has reached the target for the procedure. Most procedures can be performed if the INR is < 1.5 at the discretion of the surgeon. For very high risk bleeding surgery an INR of 1 may be required.

If the INR is elevated and surgery cannot be delayed haematology should be contacted for advice (coagulation registrar via switchboard).

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Starting bridging anticoagulation before surgery if indicated

LMWH or IV UFH can be used as bridging anticoagulation. LMWH is usually the preferred choice. However, IV UFH may be necessary due to poor renal function or if there is a need for rapid reversibility.

LMWH

Subcutaneous (SC) LMWH is commonly self-administered by the patient or relative/carer at home and does not usually require therapeutic drug monitoring. Suitable arrangements with the practice or district nurse should be made for those patients who are unable to self-administer. Patients or carers should be taught to self-administer whenever possible

Patients prescribed bridging with LMWH should stop their warfarin for 5 days before surgery. LMWH should be started when the INR drops below the lower end of the target range which is usually for the 3 days prior to the procedure [6].

Patients should be weighed prior to starting therapy with LMWH and the weight used to calculate the required dose of LMWH. Use of total body weight is appropriate for doses of LMWH in obese patients [7]. For patients >100 Kg and up to 150 Kg alternative dosing is needed (see below). For any patients >150Kg use a cut off of 150Kg.

Renal function must be considered when prescribing LMWH as it is renally excreted and can accumulate in severe renal impairment. Creatinine clearance should be calculated using Cockroft and Gault and adjusted body weight for high BMI. Adjusted body weight can be calculated here.

Therapeutic Dose LMWH

*1.5mg/Kg once daily up to a maximum dose of 150mg. For patients > 100kg use 0.75mg/kg BD omitting the evening dose the day before surgery to a maximum of 150kg. Anyone over 150kg dosing is capped for 150Kg.

The last dose of therapeutic LMWH should be given at least 24 hours before surgery which is usually at 08:00am the day before the procedure. When patients are >100Kg and on twice daily dosing the evening dose of enoxaparin the day before surgery is to be omitted. If the surgical team requests and especially if the surgery is associated with a high risk of bleeding or when using epidural or spinal anaesthesia then it may also be that a reduced dose (e.g. half dose) on the day prior to surgery is requested and this should be communicated by the surgeon or anaesthetist. [5, 6]

For patients with CrCl <20mL/min commenced on treatment dose enoxaparin antifactor Xa monitoring may be needed if continued longer than the expected three days  prior to surgery. To ascertain if therapeutic take a 4 hour post enoxaparin dose antifactor Xa level aiming for 0.5-1.0 after the 3rd consecutive dose. To ensure not accumulating with renal impairment take a trough level prior to the 5th consecutive dose aiming for <0,2, If there are concerns about these levels then to follow up with haematology.

Summary of pre-operative anticoagulant management

*If patients are on twice daily dosing it should be administered at 08:00 and 20:00. For patients on twice daily dosing of enoxaparin, the last dose prior to surgery should be administered at 08:00 on the morning before the day of surgery.

Unfractionated heparin

Administration of IV UFH involves close monitoring of the APTT ratio and hospital admission. IV UFH can be considered if the patient is undergoing a procedure where immediate or rapid reversibility is required or those with severe renal impairment where there is a risk of accumulation of LMWH.

Patients requiring IV UFH should stop warfarin 5 days pre op and be admitted to hospital 3 days prior to surgery to start IV UFH once the INR drops below the lower end of the therapeutic range.

IV UFH should be stopped 6 hours prior to surgery and the APTT should be checked urgently at 2 hours before surgery to ensure that it has normalised. If the APTT has not normalised, surgery should be deferred.

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Monitoring for heparin induced thrombocytopenia

Heparin induced thrombocytopenia can occur following exposure to any kind of heparin including UFH and LMWH. It usually presents between days 4-14 of heparin therapy but can occur at 24 hours if a patient has received any form of heparin in the preceding three months.

All patients receiving any kind of heparin should have a platelet count before starting treatment and regular platelet monitoring is required until day 14 of unfractionated heparin therapy.

For further information see The Management of Heparin Induced Thrombocytopenia and Thrombosis.

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Assessing the risk of post-operative bleeding

The risk of post-operative bleeding is based on the risk of bleeding associated with the surgery or procedure and the administration of anticoagulation combined with an assessment of postoperative haemostasis. This risk is dependent on the dose of anticoagulant and proximity to surgery.

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Restarting bridging anticoagulation after surgery

The administration of LMWH or IV UFH after surgery increases the risk of post-operative bleeding.

LMWH induces a rapid anticoagulant effect, with the potential for a detectable anticoagulant effect to occur within 1 hour and a peak anticoagulant effect to occur within 3 – 5 hours after administration. LMWH should be reintroduced with caution post operatively especially when haemostasis is not secured.

In surgery with a high bleeding risk individual risk assessment is required regarding the timing of reintroduction of therapeutic LMWH. Deferring therapeutic anticoagulation is usually the safer option. Prophylactic doses of LMWH may be given, commencing no sooner than 6 hours after surgery if haemostasis is achieved and with the agreement of the surgeon. This should be assessed individually for each patient taking in to account the indication for anticoagulation. If there is a high risk of postoperative bleeding, full therapeutic doses of LMWH should be deferred until at least 48 hours after surgery. [4]

Renal function must be considered when prescribing LMWH as it is renally excreted and can accumulate in severe renal impairment. Creatinine clearance should be calculated using Cockroft and Gault and adjusted body weight for high BMI

Prophylactic Dose LMWH

*For patients <50kg or ≥100kg see LMWH prophylactic dosing in adults at extremes of body weight

Therapeutic Dose LMWH

*1.5mg/Kg once daily up to a maximum dose of 150mg. For patients > 100kg use 0.75mg/kg BD omitting the evening dose the day before surgery to a maximum of 150kg. Dosing is capped at 150Kg for anyone over 150kg please contact the clotting reg for post-operative advice on dosing (will be capped for 150Kg) and need for anti-factor Xa monitoring.

Following major surgery more cautious escalation to therapeutic LMWH doses may be needed ie consideration may be given to splitting the dose to a twice daily regime (i.e. two half doses), this is to be discussed with the clinical team(s).

Patients with spinal/epidural catheters

A minimum of 24 hours must pass between spinal/epidural catheter insertion or removal and the last therapeutic dose of LMWH or 12 hours for prophylactic doses of LMWH.

For patients at a high risk of thromboembolism requiring therapeutic LMWH consideration should be given to an alternative route for opioid analgesia instead of epidural analgesia.

Therapeutic LMWH must not be restarted in patients with recently removed epidural catheters without discussing the individual case with a senior anaesthetist. In general, for prophylactic and therapeutic doses of LMWH, doses may be administered after 4 hours after removal of the catheter provided the procedure has been straightforward and the anaesthetist has been consulted.

For further information and guidance see Delivery of Epidural and Paravertebral Analgesia in Adult Acute Pain Management

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Restarting warfarin after surgery

Once oral intake is re-established, there is adequate haemostasis and the patient is unlikely to need to undergo any further surgical interventions consider restarting warfarin on the day of surgery or after 24 hours. Check INR prior to restarting warfarin after surgery.

Please note if any medications that interact with warfarin have been started or stopped during admission the patient’s usual maintenance dose may need altering.

Resume warfarin with either [4]

• Patients usual maintenance dose
• Two initial loading doses as outlined in the table below providing INR <1.3

Restarting warfarin with two initial loading doses post operation providing INR <1.3

For patients on parenteral bridging anticoagulation with LMWH or UFH this should be continued until the INR is above the lower end of the target range. Resuming warfarin with two initial loading doses leads to faster achievement of therapeutic INRs and may therefore lead to a shorter duration of parenteral anticoagulant which is generally a lot more acceptable to patients [8].

Warfarin must be prescribed on the variable dose section of eMEDs:

It should appear like so on the eMEDs chart:  

For inpatients, check INR preferably on a daily basis but a minimum of alternate days. 

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Discharging patients

All patients who have restarted warfarin following an elective procedure should have an anticoagulant clinic appointment arranged within 2 - 5 days of discharge as deemed clinically appropriate.

If a patient is being discharged on bridging LMWH alongside warfarin they should be booked into a consultation clinic appointment within the Trust rather than a community clinic. An adequate supply of LMWH must be given on discharge, Most patients take 7-10 days to get their INR back into therapeutic range so will need 7-10 days of enoxaparin in total from when they recommence warfarin. For patients under the care of the Leeds Anticoagulation Service, please follow this link . The referral form to complete and then email address to send to is situated here. If patients are under the care of an out of area Anticoagulation Service, direct contact must be made with them to arrange follow up, please see previous link for more guidance.

Patients with unstable INRs or those who require closer monitoring may need to be brought back to the discharging ward for an INR check if INR is very labile or prompt follow up by the anticoagulant service is unavailable for example if patient is discharged over a weekend or on a bank holiday.

Provide clear verbal and written instructions regarding anticoagulation management to the patient. Dosing and next clinic appointment information should be documented within the clinical section of the eDAN and not attached to the drug itself within the medicines. If discharging a patient on a weekend or out of hours and follow up clinic appointment information is unconfirmed then please document dosing instructions on clinical section of eDAN and note clearly that appointment information needs relaying to the patient.

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Cancelled Surgery

Cancelling elective surgery for patients who have been bridged with LMWH should be avoided if possible. It may lead to inappropriate anticoagulation management or an increased duration of bridging even if warfarin is restarted. In the event of elective surgery being cancelled, confirm the patient’s current location, whether they have been issued with another date for surgery and how many days warfarin has been stopped.

New date of surgery within the next two weeks

• Consider continuing to temporarily withhold warfarin and maintain on LMWH only
• Discuss with the patient their preference as this will mean daily injections for a prolonged period
• Contact warfarin clinic to inform them of the management plan
• If cancelled prior to attending hospital, liaise with the general practitioner to ensure an adequate supply of LMWH is maintained. Tinzaparin - Amber Drug Guidance for Bridging Therapy in Patients Requiring Interruption to their Regular Oral Anti-coagulation Prior to an Elective Procedure is available to support prescribing within primary care
• If cancelled on attending hospital, ensure an adequate supply of LMWH is maintained by providing more if necessary, to be supplied on an outpatient prescription

New date of surgery not confirmed or in more than two weeks time

• Restart warfarin
  • If warfarin has been stopped for ≤ 2 days - restart usual maintenance warfarin dose
  • If warfarin has been stopped for 3 - 4 days
    • if usual warfarin dose <12mg - give 1.5x usual dose for one day then continue on usual maintenance dose
    • if usual warfarin dose ≥12mg - give 1.3x usual dose for one day then continue usual maintenance dose
  • ≥ 5 days – restart with two initial loading doses as outlined in the restarting warfarin following surgery section above
• Continue enoxaparin until INR is above the lower end of the target range
• Contact warfarin clinic to arrange an INR test within the next 2 - 5 days as deemed clinically appropriate  
• If cancelled prior to attending hospital, liaise with warfarin clinic or the general practitioner to ensure an adequate supply of LMWH is maintained. Tinzaparin - Amber Drug Guidance for Bridging Therapy in Patients Requiring Interruption to their Regular Oral Anti-coagulation Prior to an Elective Procedure is available to support prescribing within primary care
• If cancelled on attending hospital, ensure an adequate supply of LMWH is maintained by providing more if necessary

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