Warfarin - Guidance for Starting and Maintaining Adult Patients

Publication: 09/09/2011  
Next review: 01/12/2022  
Clinical Guideline
CURRENT 
ID: 1409 
Approved By: Trust Clinical Guidelines Group 
Copyright© Leeds Teaching Hospitals NHS Trust 2019  

 

This Clinical Guideline is intended for use by healthcare professionals within Leeds unless otherwise stated.
For healthcare professionals in other trusts, please ensure that you consult relevant local and national guidance.

Guidance for starting and maintaining adult patients on warfarin

Aims

This guideline has been developed to promote a safe and consistent approach to achieving therapeutic anticoagulation in adults with the vitamin K antagonist, warfarin.  It addresses starting treatment, cautions and contra-indications and drug interactions.  The guideline also covers the safe and appropriate management of patients at discharge.  It aims to provide a practical guide for medical and other healthcare professionals involved in starting and maintaining patients on warfarin.

Back to top

Background

Warfarin is the most frequently prescribed oral vitamin K antagonist anticoagulant in the UK. Acenocoumarol may be used in some patients who experience problems with hair loss, headache, or rash on warfarin.  Both drugs require regular monitoring and in some patients frequent dose adjustment to maintain the desired therapeutic action (measured by the international normalized ratio INR) and minimise adverse bleeding events. The National Patient Safety Agency (NPSA) issued a patient safety alert in March 2007 on actions that can make anticoagulant therapy safer.  Anticoagulants are one of the classes of medicines most frequently identified as causing preventable harm and admission to hospital.  Managing the risks associated with anticoagulants can reduce the chance of patients being harmed in the future.  This guideline will in part address some of the actions listed in the alert.
The use of the direct oral anticoagulants (DOACs) will not be covered in this guideline. Advice on the use of DOACS can be found in http://nww.lhp.leedsth.nhs.uk/common/guidelines/detail.aspx?id=3365 and
http://nww.lhp.leedsth.nhs.uk/common/guidelines/detail.aspx?id=3974

Back to top

Treatment / Management

Indications for anticoagulation

The table below shows the indications for oral anticoagulation and the target INR for a vitamin K antagonist.

Indication

Target INR

Pulmonary embolus 2.5
Proximal deep vein thrombosis 2.5
Calf vein thrombosis 2.5
Recurrence of venous thromboembolism when no longer on anticoagulant therapy 2.5
Recurrence of venous thromboembolism whilst on warfarin therapy with therapeutic INR 3.5
Symptomatic inherited thrombophilia 2.5
Antiphospholipid syndrome 2.5
Non-valvular atrial fibrillation 2.5
Valvular atrial fibrillation 2.5
Elective cardioversion (pre-procedure) 3.0
Elective cardioversion (post-cardioversion procedure) 2.5
Left ventricular thrombus 2.5
Mural thrombus 2.5
Mechanical prosthetic heart valve - aortic See separate table
Mechanical prosthetic heart valve - mitral See separate table
Peripheral artery thrombosis 2.5
Arterial grafts 2.5
arterial embolism 2.5

Recommended target INRs for mechanical heart valves
(reproduced from BCSH Guidelines 2011 3 )

Prosthesis Thrombogenicity

INR target
No patient risk factors

INR target
Patient-related risk factors *

Low

2.5

3.0

Medium

3.0

3.5

High

3.5

3.5 **

 
*  Patient-related risk factors for thrombosis: mitral, tricuspid or pulmonary position; previous arterial thromboembolism; atrial fibrillation; left atrium diameter >50mm; mitral stenosis of any degree; left ventricle ejection fraction <35%; left atrial dense spontaneous echo contrast.
Note that new On-X type valves often require a lower target of 2 for aortic position after first 3 months. On-X in the mitral position require an INR target of 3.

**  Target INR was 4.0 one study.

Contra-indications

  • Hypersensitivity to the active substance
  • Haemorrhagic stroke
  • Clinically significant bleeding
  • Within 72 hours of major surgery with risk of severe bleeding
  • Within 48 hours postpartum.
  • Pregnancy (first and third trimesters)
  • Drugs where interactions may lead to a significantly increased risk of bleeding
  • Uncontrolled hypertension

Cautions

  • risk of serious haemorrhage (e.g. concomitant NSAID use, recent ischaemic stroke, bacterial endocarditis, previous gastrointestinal bleeding
  • Patients with protein C deficiency are at risk of developing skin necrosis when starting warfarin treatment. In patients with protein C deficiency, therapy should be introduced without a loading dose of warfarin even if heparin is given. Patients with protein S deficiency may also be at risk and it is advisable to introduce warfarin therapy slowly in these circumstances.

Before commencing anticoagulant therapy

Check baseline coagulation screen (INR, PT (prothrombin time), APTT (activated partial thromboplastin time)), full blood count, U&Es and liver function tests.

Ensure INR is <1.3 before treatment.  If INR 1.3 or more consider reasons for raised INR and consider if warfarin is definitely indicated. Repeat and if still raised discuss with haemostasis/thrombosis haematology team

Choose appropriate loading regimen

A) Starting warfarin therapy - rapid anticoagulation (DVT and PE)
B) Starting warfarin therapy - slow induction of anticoagulation (AF - in patients not requiring heparinisation)
C) Managing patients re-starting oral anticoagulation (warfarin) therapy

A)  Starting warfarin therapy - rapid anticoagulation

Rapid anticoagulation is used where patients need to achieve their target INR as quickly as possible.  It takes five to ten days for the full effects of warfarin to be seen and in the early stages of treatment with warfarin a hypercoagulable state may be induced due to the rapid depletion of natural anticoagulant protein C.  Rapid anticoagulation is achieved using heparin; enoxaparin is the low molecular weight heparin of choice at Leeds Teaching Hospitals NHS Trust for this indication. Low molecular weight heparin should be continued for at least 5 days and until the INR is ≥2 for at least 24 hours, whichever is the longest.

The standard warfarin loading dose regimen (Appendix 1) is suitable for younger patients. 

Some patients are likely to be sensitive to warfarin*:

  • Age over 65 years
  • Prolonged baseline INR
  • Cardiac failure
  • Liver disease
  • Abnormal renal function - often have lower dose requirements and labile INR’s. Often adopt a more cautious approach to prevent over anti-coagulation in this group of patients. Patients with an eGFR of 30–59 mL/min/1.73 m2 tend to need a 10% lower maintenance dose, while those with levels of eGFR <30 mL/min/1.73 m2 a 20% lower dose. This is probably related to the down-regulation of cytochrome P450 in chronic kidney disease.
  • Nutritional deficiencies (hypoalbuminaemia, reduced intake or absorption of vitamin K)
  • Body weight < 60kg
  • Concomitant therapy with a drug known to potentiate warfarin (see BNF appendix 1) 
  • acute illness or immediately post cardiac surgery
  • treated with drugs which potentiate warfarin e.g. amiodarone, antibiotics, antifungals (see BNF appendix 1)

In these patients, please refer to Appendix 1 for the alternative regimen to use in patients likely to be sensitive *.
If patients are very elderly, very low body weight or very poor renal function consider a lower loading dose of 3mg and discuss with ward pharmacist

1) Prescribing warfarin
 
Patients requiring rapid anticoagulation should follow the warfarin loading dose regimen as shown above

Refer to Appendix 1 for Standard and sensitive warfarin loading dose regimen

If at day 4, patients are requiring greater than warfarin 10mg daily, consult a senior clinician or specialist anticoagulation pharmacist for advice on subsequent dosing.

2)  Commencing heparin as part of the rapid anticoagulation process

Rapid warfarin loading should be initiated in conjunction with therapeutic dose parenteral heparin.  Parenteral anticoagulation should continue for at least 5 days and until the INR is ≥2 for at least 24 hours, whichever is the longest.  Enoxaparin 1.5mg/kg by subcutaneous injection  is the low molecular weight heparin (LMWH) of choice for venous thromboembolism.

If creatinine clearance (CrCl) < or equal to 30mL/min (severe renal impairment) use enoxaparin 1mg/kg once daily Unfractionated heparin can be used if enoxaparin not appropriate.

It is not necessary to routinely monitor anti-factor-Xa activity in patients receiving LMWH. In patients with severe renal impairment, anti-factor Xa levels can be monitored and dose adjustments made accordingly. Seek advice from haematology.

Treatment with UFH is monitored using the APTT ratio, where the target range is 1.5-2.5.  Please refer to the heparin prescription chart for dosing and monitoring.

B)  Starting warfarin therapy - slow induction of anticoagulation (Atrial Fibrillation and stroke - in patients not requiring heparinisation)

Patients with atrial fibrillation are at an increased risk of thromboembolism and stroke.  Slow induction of anticoagulation is suitable in these patients (Janes et al 2004).  This regimen takes longer to achieve a stable INR but it avoids the potential hypercoagulability seen with rapid anticoagulation and results in fewer episodes of over anticoagulation.  These patients do not require additional anticoagulation with either UFH or LMWH until therapeutic and slow induction is usually carried out in an outpatient setting. It can take 3-4 weeks before therapeutic anticoagulation is achieved.

1) Prescribing warfarin

Usual slow induction regimen:  
2mg or lower daily dose - for patients with any of the cautionary risk factors listed below. Dose continued for 7 days, then check the INR on day 8.  An earlier INR check may be arranged if the patient has several (4 or more) of the cautionary risk factors listed below.

3mg daily (standard dose) - continue dose for 7 days, then check INR on day 8.

4mg daily- continue for 7 days, then check INR on day 8 may be used for larger patients with no cautionary risk factors). 

C) Managing patients re-starting oral anticoagulation (warfarin) therapy

Where warfarin therapy has been omitted for a period of time, all these patients should have a baseline INR checked before re-commencing warfarin therapy.  If a patient’s warfarin was stopped due to over-anticoagulation or bleeding, it is not appropriate to restart the patient’s usual maintenance dose. 

Metallic valve replacements, acute venous thromboembolism in the last 4 weeks, AF related stroke in last 4 weeks or clinical need for immediate rapid anticoagulation

If the baseline INR is therapeutic, re-commence warfarin at the patient’s usual maintenance dose.

If the baseline INR is below 1.8, the patient should re-commence anticoagulation with warfarin, usually using normal dose + 50% for 2 days then back on usual dose (if no risk factors listed above) and either LMWH or UFH; once the INR has been therapeutic for two consecutive days, discontinue LMWH or UFH.

Chronic venous thromboembolism (> 4 weeks since acute event)

Recommence warfarin at the same dose as prior to admission (as long as admission not related to over-anticoagulation or adverse events such as bleeding). Ensure the patient is on prophylactic LMWH for VTE prevention

Atrial fibrillation (no previous stroke or TIA)

Recommence warfarin at the same dose as prior to admission (as long as admission not related to over-anticoagulation or adverse events such as bleeding).  In cases where the reason for the patient’s admission was related to over-anticoagulation or bleeding, reassess the choice of anticoagulant and consider re-loading with slow induction regimen using lower dose than on admission if warfarin to continue.

Patients with Atrial fibrillation AND previous stroke or TIA or multiple other risk factors

Consider clinical need for immediate rapid anticoagulant (see above)

Target INRs and loading schedules

The target INR range, indication and duration of anticoagulation should be indicated on the patients Electronic Discharge Advice Note (EDAN) , anticoagulant referral letter and on Emeds.

Indication

Target INR

Loading schedule

Duration of anticoagulation

Pulmonary embolus 2.5 Rapid At least 3 months
Proximal deep vein thrombosis 2.5 Rapid At least 3 months
Calf vein thrombosis 2.5 Rapid Three months
Recurrence of VTE when no longer on warfarin 2.5 Rapid Consider long term
Recurrence of VTE while on warfarin 3.5 Rapid Consider long term
Antiphospholipid syndrome 2.5 Rapid Consider long term
Atrial fibrillation 2.5 Slow Long term
Cardioversion 2.5 or 3.0 Slow At least 3 weeks before and 4 weeks after procedure
Mural thrombus 2.5 Rapid Three months
Cardiomyopathy 2.5 Rapid Long term
Mechanical prosthetic heart valve 2.5, 3.0 or 3.5 Rapid Long term
Cancer-associated VTE Therapeutic dose LMWH   6 months

Continued anticoagulation beyond the initial period of 3 months

  • Long-term anticoagulant therapy is NOT recommended in patients with VTE provoked by surgery
  • Long-term anticoagulant therapy is NOT recommended in patients with VTE provoked by non-surgical transient trigger factors
  • Patients with unprovoked proximal DVT or PE should be considered for long-term anticoagulation, taking into account information that may help predict risk of recurrence and risk of bleeding in the individual patient
  • Long-term anticoagulant therapy is NOT recommended in patients with VTE confined to the calf (i.e. not extending into the popliteal vein)

Back to top

Drug Interactions

Many drugs and herbal medicines interact with warfarin.

Please refer to Appendix 2 for a list of clinically significant interactions with warfarin.

This list is not exhaustive, please consult the BNF, your ward pharmacist or Medicines Information (Ext 65377) for further information/advice

Back to top

Discharge arrangements

Warfarin Patient Information Checklist

The NPSA Patient Safety Alert issued in March 2007 on actions to make anticoagulants safer requires that all patients prescribed anticoagulants should receive appropriate written and verbal information at the start of therapy, at hospital discharge , on the first anticoagulant clinic appointment and when necessary throughout the course of their treatment.

At LTHT, all patients prescribed warfarin should receive a yellow anticoagulant book and verbal reinforcement of the messages conveyed in this booklet.  Yellow Anticoagulant Books are supplied directly from the ward (NOT Pharmacy).

The following points must be discussed with the patient when they are being given information on warfarin.

  • Indication for warfarin
  • Duration of treatment
  • Need for blood tests and keeping appointments
  • Target INR range and what INR means
  • If unexpected bruising or bleeding occurs, consult GP
  • If they have any dark tar like stools, attend A&E
  • If trauma, head injury, thunder-clap type headache or severe bleeding, attend A&E
  • Dose of warfarin and colour of tablets
  • Take warfarin at the same time each day
  • What to do if doses are missed
  • What to do if doubled up on doses
  • Further supplies of warfarin to be obtained from GP
  • Avoid aspirin and NSAIDs, unless prescribed intentionally
  • If any new medications are started or stopped, inform anticoagulation service
  • Avoid sudden changes in diet.  No crash dieting or binge eating.
  • Women and Men may drink within the national advised alcohol limits (14 units per week), providing their alcohol consumption is spread evenly over the whole week.  No binge drinking.
  • Avoid saving units of alcohol for one night later in the week
  • Take precautions to prevent pregnancy (if applicable)

Responsibility for ensuring patients have received appropriate warfarin patient information

An explanation of warfarin treatment to the patient may be undertaken by any suitably qualified pharmacist, pharmacy technician (having successfully completed the necessary training accreditation) nurse or doctor. 

For wards with no Pharmacist cover or discharge out of hours, the responsibility of warfarin counselling falls to the doctor prescribing the discharge prescription.

 Anticoagulation Clinic Referrals

All patients discharged on warfarin should be referred to the Leeds Oral Anticoagulant Service. 

If the patient is not monitored by Leeds please refer to their original clinic - see details of other Yorkshire and Humber clinics on the LHP anticoagulation pages.

All referrals should be completed online Via Patient Pass under Haematology (Anticoagulation).

See link to complete referral forms for new or existing patients on warfarin. http://lthweb.leedsth.nhs.uk/sites/clinical-haematology/haemostasis-and-thrombosis/anticoagulation-1/anticoagulation/warfarin-e-referrals

If the patient requires any form of hospital transport, it is the responsibility of the discharging ward to arrange this.

Referrals should NEVER delay discharge. A member of the anticoagulation team will be in touch with the patient or the ward to inform them of an appointment time.

Discharge Actions

Actions for the prescriber:

  • Complete the Electronic Discharge Advice Note - EDAN (discharge prescription) with details of the indication for warfarin, dose on discharge and intended duration of treatment.
  • Complete all sections of the yellow anticoagulant book, including the dose on discharge.
  • Give the patient an explanation of their warfarin treatment (where this has not already been completed by the Pharmacist/Pharmacy Technician)
  • Inform the patient if they are to be monitored by Leeds the anticoagulant service will be in touch

Actions for the pharmacist/pharmacy technician

  • Check that the yellow anticoagulant book has been completed correctly with the information above
  • Give the patient an explanation of their warfarin treatment

Actions for the Nurse responsible for discharging the patient
Ensure that all patients discharged on warfarin have:

  • A yellow anticoagulant book
  • Received written and verbal information on their warfarin treatment
  • Sufficient supplies of the correct strengths of warfarin
  • A fully completed yellow anticoagulant book with a written dose of warfarin until their next anticoagulant clinic appointment
  • Date and time of anticoagulant clinic appointment

Back to top

Discontinuation of anticoagulation

The duration of anticoagulation treatment should always be stated when starting treatment based on the clinical indication for anticoagulation, and other risk factors the patient may have.  Where the duration of treatment is a deviation from the recommendations made, the reason for this should be stated in the medical notes, on the discharge prescription and on the anticoagulant referral letter.

The current recommendations are that oral anticoagulant therapy can be discontinued abruptly when the duration of therapy is complete.
Please remember to let the anticoagulant office know if a patient’s warfarin is discontinued.

You can send an email to inform them: Leedsth-tr.leedsacsreferral@nhs.net.

Back to top

Appendix 2

Clinically significant drug interactions involving warfarin

This list is not exhaustive, please consult the BNF, your ward pharmacist or Medicines Information (Ext 65377) for further information/advice

Drug

Interaction

Acitretin

Decreased anticoagulant effect

Alcohol

Anticoagulant control may be affected by major changes in consumption of alcohol; likely increased INR with increased alcohol consumption

Anabolic steroids

Increased anticoagulant effect and bleeding seen. 

Amiodarone

Anticoagulant effect may be significantly increased.

Aspirin

Increased risk of bleeding

Antibacterials

Increased anticoagulant effect may be seen with cephalosporins, quinolones, tetracyclines, trimethoprim, macrolides, metronidazole and broad spectrum penicillins.

Decreased anticoagulant effect may be seen with rifampicin.

Antidepressants

Possible increased anticoagulant effect with venlafaxine, SSRIs, mirtazepine.

Possible decreased anticoagulant effect with St John’s Wort.  Avoid concomitant use.

Possibly increased or decreased anticoagulant effect with tricyclics.

Anti-diabetics

Possibly increased anticoagulant effect with exenatide

Possibly increased anticoagulant effect with sulphonylureas.

Anti-epileptics

Anticoagulant effect of warfarin possibly enhanced by valproate.

Anticoagulant effect of warfarin reduced by carbamazepine, primidone and phenytoin

Anti-fungals

Anticoagulant effect of warfarin enhanced by fluconazole, itraconazole, ketoconazole, voriconazole and miconazole.

Anticoagulant effect of warfarin reduced by griseofulvin.

Anti-virals

Contact Anti-Retroviral Specialist or Pharmacy Medicines Information for advice.

Azathioprine

Possible decreased anticoagulant effect

Barbiturates

Decreased anticoagulant effect

Clopidogrel

Increased anticoagulant effect

Corticosteroids

Increased or decreased anticoagulant effect.

Cranberry Juice

Increased anticoagulant effect. Advised not to drink
Avoid concomitant use.

Cytotoxics

Contact Pharmacy Medicines Information for advice

Dipyridamole

Increased anticoagulant effect due to antiplatelet action

Disulfiram

Increased anticoagulant effect

Entacapone

Increased anticoagulant effect

Enteral feeds

Reduced anticoagulant effect (when Vitamin K present in enteral feeds)

Evening Primrose Oil

May increase risk of bruising and bleeding

Fish oils

May increase risk of bleeding

Flu vaccine

May increase INR. Test within 7 days

Garlic

Case reports of increased anticoagulation effect

Glucosamine

Increased anticoagulant effect
Avoid concomitant use

Grapefruit

Inhibits metabolism of warfarin and may increase INR
AVOID

Hormone antagonists

Increased anticoagulant effect with bicalutamide, toremifene, danazol, flutamide and tamoxifen

Levamisole

Increased anticoagulant effect

Multivitamins

Caution - may contain Vitamin K

Oestrogens

Increased or decreased anticoagulant effect

Progestogens

Increased or decreased anticoagulant effect

Proton Pump Inhibitors and H2-antagonists

Increased anticoagulant effect with cimetidine, esomeprazole, omeprazole and pantoprazole

Statins and Lipid-regulating drugs

Increased or decreased anticoagulant effect with colestyramine

Increased anticoagulant effect with fibrates, fluvastatin and simvastatin.

Possible increased anticoagulant effect with ezetimibe and rosuvastatin.

Transient reduction in anticoagulant effect with atorvastatin

St John’s Wort

Anticoagulant effect of warfarin possibly reduced by St John’s Wort.  Avoid concomitant use.

Thyroid hormones

Increased anticoagulant effect

Vitamin C

May decrease effect of Warfarin

Vitamin E

May increase effect of Warfarin

Vitamin K

Anticoagulant effects of Warfarin are reduced or abolished

Provenance

Record: 1409
Objective:

To provide evidence-based recommendations for the management of adult patients requiring warfarin therapy.

Clinical condition:

All conditions requiring anticoagulation with warfarin

Target patient group: All adult patients requiring anticoagulation treatment with warfarin
Target professional group(s): Secondary Care Doctors
Secondary Care Nurses
Pharmacists
Adapted from:

Evidence base

  1. National Patient Safety Agency.  Patient Safety Alert 18 - Actions that can make anticoagulant therapy safer (2007).  Available at: www.npsa.nhs.uk [Accessed 14th November 2016].
  2. Baglin TP, Keeling DM, Watson HG.  Guidelines for oral anticoagulants (warfarin), Fourth Edition, 2011.  British Journal of Haematology. 20  Available at: www.bcshguidelines.com [Accessed 14th November 2016].  Grade A evidence recommendation
  3. Baglin TP et al.  Recommendations from the British Committee for Standards in Haematology and the national patient Safety Agency.  Safety indicators for inpatient and outpatient oral anticoagulant care.  British Journal of Haematology. 2007; 136: 26-29.   Available at: www.bcshguidelines.com [Accessed 14th November 2016].
  4. Campbell et al. Guidelines on the investigation and management of venous thrombosis at unusual sites. British Journal of Haematology, 2012, 1: 28-38.  Available at: www.bcshguidelines.com [Accessed 14th November 2016]
  5. Janes S et al. Safe introduction of warfarin for thrombotic prophylaxis in atrial fibrillation requiring only weekly INR. Clin Lab Haem, 2004, 26: 43-47. Grade B evidence recommendation.
  6. BNF 72: September 2010. Available at: www.bnf.org [Accessed 14th November 2016]. Grade A evidence recommendation
  7. SPC Warfarin 0.5mg tablets BP - last updated 23/10/2012. Available at: www.medicines.org.uk [Accessed 14th November 2016].
  8. SPC Innohep 20,000 IU/ml and Innohep syringe 20,000 IU/ml - last updated 29/09/2016.  Available at: www.medicines.org.uk [Accessed 14th November 2016].
  9. SPC Clexane pre-filled syringe - last updated 06/08/15.  Available at: www.medicines.org.uk [Accessed 14th November 2016].
  10. SPC Heparin sodium 1000 IU/ml ampoule, solution for infusion (Leo Laboratories Ltd) - last updated 07/12/2007.  Available at: www.medicines.org.uk [Accessed 16th March 2011].
  11. Hughes et al. Anticoagulation in chronic kidney disease patients—the practical aspects. Clinical Kidney Journal, 2014. Vol 7, Issue 5. Available athttp://ckj.oxfordjournals.org/content/7/5/442.full. [accessed 14th November 2016]
  12. Common interactions with Warfarin. Available online at Anticoagulation Europe.
    http://www.anticoagulationeurope.org/publications/common-interactions-with-warfarin. [accessed 14th November 2016].

Approved By

Trust Clinical Guidelines Group

Document history

LHP version 2.1

Related information

This guideline is for use in adults only. For guidance on the use of anticoagulants in children see the ‘Protocol for the use of anti-thrombotic treatment in children’

Equity and Diversity

The Leeds Teaching Hospitals NHS Trust is committed to ensuring that the way that we provide services and the way we recruit and treat staff reflects individual needs, promotes equality and does not discriminate unfairly against any particular individual or group.