Anticoagulants - Guidance for Starting and Maintaining Adult Patients
|Publication: 09/09/2011 --|
|Last review: 01/12/2019|
|Next review: 01/12/2022|
|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.
Guidance for starting and maintaining adult patients on warfarin
- Starting warfarin therapy - rapid anticoagulation (DVT and PE)
- Starting warfarin therapy - slow induction of anticoagulation (AF - in patients not requiring heparinisation)
- Managing patients re-starting oral anticoagulation (warfarin) therapy
- Drug Interactions
- Discharge arrangements
- Discontinuation of anticoagulation
- Appendix 1
- Appendix 2
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.
It is estimated in the UK, there are approximately 500 000 patients currently prescribed oral anticoagulant drugs. Warfarin is the most frequently prescribed vitamin K antagonist oral anticoagulant. The other less commonly prescribed vitamin K antagonist oral anticoagulant is acenocoumarol. These drugs require monitoring and frequent dose adjustment to maintain the desired therapeutic action 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 detail.aspx?id=3365 and
Indications for anticoagulation
The table below shows the indications for oral anticoagulation and the target INR for a vitamin K antagonist.
|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|
|Non-rheumatic atrial fibrillation||2.5|
|Atrial fibrillation due to rheumatic heart disease, congenital heart disease and thyrotoxicosis||2.5|
|Elective cardioversion (pre-procedure)||3.0|
|Elective cardioversion (post-cardioversion procedure)||2.5|
|Patients with mitral stenosis or regurgitation who have atrial fibrillation or a history of systemic embolism or left atrial thrombus or an enlarged left atrium||2.5|
|Mechanical prosthetic heart valve - aortic||See separate table|
|Mechanical prosthetic heart valve - mitral||See separate table|
|Bioprosthetic heart valve - mitral position||2.5|
|Bioprosthetic heart valve and left ventricular thrombus at surgery should receive warfarin until clot resolved||2.5|
|Bioprosthetic valve - with other prothrombotic risk factors - AF and low ejection fraction||2.5|
|Ischaemic stroke without atrial fibrillation||Not indicated|
|Retinal vessel occlusion||Not indicated|
|Peripheral artery thrombosis||2.5 if anticoagulated|
|Arterial grafts||2.5 if anticoagulated|
|Coronary artery thrombosis||2.5 if anticoagulated|
|Coronary artery graft||Not indicated|
|Coronary angioplasty and stents||Not indicated|
|Intermittent claudication |
(However, patients who suffer acute arterial embolism and proceed to embolectomy should be considered for long-term anticoagulation with warfarin with an INR target of 2·5)
Recommended target INRs for mechanical heart valves
(reproduced from BCSH Guidelines 2011 3)
|Prosthesis Thrombogenicity|| |
* 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.
** Target INR was 4.0 one study.
- Known hypersensitivity to the anticoagulant
- Actual or potential haemorrhage conditions e.g. peptic ulcer, aneurysm or to patients with uncontrolled hypertension
- Infective endocarditis
- Recent organ biopsy (consult specialists in clinical area)
- Recent trauma or surgery to the head, orbit or spine (consult specialists in clinical area)
- Confirmed intracranial or intraspinal bleed
- Pregnancy - contraindication to warfarin
- 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.
- Active bleeding
Before commencing anticoagulant therapy
Check baseline INR, PT (prothrombin time), APTT (activated partial thromboplastin time) haemoglobin and platelets, renal function and liver function tests (ALT and Bilirubin).
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 Haematology
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
The rapid anticoagulation loading regimen for warfarin is suitable for all patients with the exception of those being anticoagulated for atrial fibrillation. 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; tinzaparin 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. Tinzaparin is the low molecular weight heparin (LMWH) of choice for venous thromboembolism.
Tinzaparin 175 units/kg once daily by subcutaneous injection
If creatinine clearance (CrCl) <20mL/min (severe renal impairment) use unfractionated heparin (UFH) or enoxaparin 1mg/kg once daily or discuss with renal physicians.
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.
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).
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.
Duration of anticoagulation
|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|
|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)
Many drugs and herbal medicines interact with warfarin.
Please refer to Appendix 2 for a list of clinically significant interactions with warfarin.
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 and emailed across to the Leeds Oral Anticoagulant Service.
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.
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
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: Leedsthemail@example.com.
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
Decreased anticoagulant effect
Anticoagulant control may be affected by major changes in consumption of alcohol; likely increased INR with increased alcohol consumption
Increased anticoagulant effect and bleeding seen.
Anticoagulant effect may be significantly increased.
Increased risk of bleeding
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.
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.
Possibly increased anticoagulant effect with exenatide
Possibly increased anticoagulant effect with sulphonylureas.
Anticoagulant effect of warfarin possibly enhanced by valproate.
Anticoagulant effect of warfarin reduced by carbamazepine, primidone and phenytoin
Anticoagulant effect of warfarin enhanced by fluconazole, itraconazole, ketoconazole, voriconazole and miconazole.
Anticoagulant effect of warfarin reduced by griseofulvin.
Contact Anti-Retroviral Specialist or Pharmacy Medicines Information for advice.
Possible decreased anticoagulant effect
Decreased anticoagulant effect
Increased anticoagulant effect
Increased or decreased anticoagulant effect.
Increased anticoagulant effect. Advised not to drink
Contact Pharmacy Medicines Information for advice
Increased anticoagulant effect due to antiplatelet action
Increased anticoagulant effect
Increased anticoagulant effect
Reduced anticoagulant effect (when Vitamin K present in enteral feeds)
Evening Primrose Oil
May increase risk of bruising and bleeding
May increase risk of bleeding
May increase INR. Test within 7 days
Case reports of increased anticoagulation effect
Increased anticoagulant effect
Inhibits metabolism of warfarin and may increase INR
Increased anticoagulant effect with bicalutamide, toremifene, danazol, flutamide and tamoxifen
Increased anticoagulant effect
Caution - may contain Vitamin K
Increased or decreased anticoagulant effect
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.
Increased anticoagulant effect
May decrease effect of Warfarin
May increase effect of Warfarin
Anticoagulant effects of Warfarin are reduced or abolished
|Objective:||To provide evidence-based recommendations for the management of adult patients requiring warfarin therapy.|
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
- 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].
- 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
- 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].
- 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]
- 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.
- BNF 72: September 2010. Available at: www.bnf.org [Accessed 14th November 2016]. Grade A evidence recommendation
- SPC Warfarin 0.5mg tablets BP - last updated 23/10/2012. Available at: www.medicines.org.uk [Accessed 14th November 2016].
- 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].
- SPC Clexane pre-filled syringe - last updated 06/08/15. Available at: www.medicines.org.uk [Accessed 14th November 2016].
- 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].
- 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]
- Common interactions with Warfarin. Available online at Anticoagulation Europe.
http://www.anticoagulationeurope.org/publications/common-interactions-with-warfarin. [accessed 14th November 2016].
Trust Clinical Guidelines Group
LHP version 2.0
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’
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