Warfarin

Adapted from Pisters R et al. HAS-BLED. Chest. 2010:138:1093-1100

A) Schedule for slow initiation of prophylactic and therapeutic warfarin therapy for in-patients^1,2

This schedule is intended for use where the need for rapid induction is not necessary, ie in the majority of patients. Slow initiation of warfarin is less likely to lead to bleeding problems and is preferable.

• Determine and record therapeutic indication, target INR (see below) and duration of treatment in the medical notes (and on the In-patient Oral Anticoagulant Prescription Chart if in-patient).
• Obtain pre-treatment INR. NB: INRs are inaccurate if the patient is receiving standard heparin and the APTT ratio is >3·0. Low molecular weight heparin (LMWH) does not affect the INR.
• For Venous thromboembolism (VTE) patients continue LMWH for at least 5 days and until the INR is above the lower limit of the desired therapeutic range for 24 hours, ie 2 INRs 24 hours apart. Stop the LMWH immediately if INR is greater than the upper limit of the desired therapeutic range.

Commence warfarin 2mg daily

• Check INR on days 3 and 7. (For those with: liver failure eg LFTs ≥1·5 times ULN, receiving drugs which interact with warfarin, or weighing less than 50kg a smaller starting dose may be appropriate. Discuss with Haematology before initiating therapy.)
• If INR >4·0, then omit for at least 2 days, measuring INR on the first day dose is omitted. Once INR is <3·0 recommence at 1mg daily. Check INR again after 3 days.
• If INR 3·0 to 4·0, reduce 2mg dose to 1·5mg (a 1·5mg dose to 1mg, and a 1mg dose to 0·5mg). Check INR again after 3 days.
• If INR <3·0, continue on current dose until next planned check (day 7 or day 14).
• Recheck INR after 2 weeks of anticoagulation and predict maintenance dose as follows:

•  Check INR weekly for 6 to 8 weeks. Warfarin dose is only changed when:
  • INR >4·0, but <5·0 then omit for 2 days and recommence daily dose at 20% less than previous dose. Recheck after 3 days.
  • INR >3·5 to 4·0, reduce daily dose by 20%. Recheck after 3 days.
  • INR 3·0 to 3·5, reduce daily dose by 10%. Recheck after 3 days.
  • INR <1·5 for 2 consecutive weeks, then increase daily dose by 25%. Recheck after 1 week.
  • if INR is not stable by week 6, 10% daily dose adjustments can be made weekly.

¹ Adapted from Fennerty et al, BMJ 1988; 297: 1285-8.

² Adapted from Br.J.Clin.Pham.1998; 46: 159.

B) Schedule for the slow initiation of prophylactic and therapeutic warfarin therapy for out-patients and General Practice

• For patients managed via the Haematology Service see ‘GP Referral Form for Anticoagulant Monitoring’.
• For patients managed via the GP follow the local practice guidelines.

C) Schedule for rapid initiation of warfarin therapy – hospital in-patients only

Rapid initiation of oral anticoagulation is potentially hazardous. If required in patients with newly-diagnosed venous thromboembolism discuss this with a Consultant Haematologist before initiating warfarin treatment. The Haematologist will give dosing guidance based on individual patient factors. The initial dosing regimen will vary between patients depending on whether there is increased sensitivity to warfarin, eg aged over 65, low body weight, parenteral feeding, heart failure, liver failure, prolonged baseline prothrombin time or receiving other drugs known to potentiate oral anticoagulants.

• Determine and record therapeutic indication, target INR (see below) and duration of treatment in medical notes and on the In-patient Oral Anticoagulant Prescription Chart.
• Obtain pre-treatment INR. NB: INRs are inaccurate if the patient is receiving standard heparin and the APTT ratio is >3·0. LMWH does not affect the INR.
• Check INR and prescribe warfarin daily as per dose plan agreed with the Haematologist.
• Continue LMWH for at least 5 days and until the INR is above the lower limit of the desired therapeutic range for 24 hours, ie 2 INRs 24 hours apart. Stop the LMWH immediately if INR is greater than the upper limit of the desired therapeutic range.

When completing the IDL for in-patients continuing or starting warfarin therapy, a warning box appears: ‘A tab has been created for completion’. This Anticoagulant Therapy section must be completed prior to sending the IDL to pharmacy. When the IDL has been completed the Anticoagulant Therapy letter created within it should be e-mailed to whoever is responsible for the ongoing management of the patient’s anticoagulation. This information also appears on all copies of the patient’s discharge letter and is emailed to GPs. All patients should receive verbal and written information (Oral Anticoagulant Therapy Booklets are available from Pharmacy). The nurse discharging the patient must ensure that the patient has an up-to-date completed booklet.

Prior to commencing warfarin:

• counsel patient on warfarin usage; refer to checklist in section 17.2 of SIGN 129 (requires internet connection).
• measure INR, U&Es, LFTs and FBC.
• fill in In-patient Oral Anticoagulant Prescription Chart.
• patients receiving an anti-platelet agent as primary prophylaxis for cardiovascular disease on developing an indication for warfarin should stop their anti-platelet agent.
• patients with peripheral artery disease or previous ischaemic stroke on antiplatelet therapy should stop this agent if warfarin is commenced.
• patients on aspirin or clopidogrel as secondary prophylaxis with stable ischaemic heart disease (often defined as more than 12 months following acute myocardial infarction) should stop their antiplatelet agent while being treated with warfarin.
• patients on a single antiplatelet agent less than 12 months following an acute coronary syndrome (ACS), who require to start warfarin therapy should continue aspirin therapy until 12 months post-ACS, unless they are regarded as having a high bleeding risk .
• patients on aspirin and clopidogrel/prasugrel/ticagrelor following an ACS or stent placement, who develop an indication for warfarin should be carefully assessed for bleeding risk and discussed with their cardiologist, with a view to introducing warfarin and minimising the duration of triple therapy .
• when combined warfarin and single antiplatelet agent are indicated, consider use of aspirin given the higher bleeding risk associated with clopidogrel (bcsh guidelines (2011) requires internet connection).

On discharge:

Complete IDL including the Anticoagulant Therapy section. Telephone GP regarding INR monitoring. Oral Anticoagulant Therapy booklets can be obtained from Pharmacy. GPs may order booklets from the Supplies Department, Raigmore Hospital (code WMZ 045).

Because of the long half-life of oral anticoagulant drugs the full effect of a dose change is not seen for 3 to 4 days in many patients. For those on weekly dosing regimens it will be longer.

Most dose changes should be subtle (ie 10 to 20% of the current average daily dose at a time). The change may well represent less than 0·5mg in patients who only require small doses of warfarin or acenocoumarol and thus an alternate day or weekly dosing regimen may be required to deliver such a change.

There is a wide range of drug and dietary interactions with coumarins which should be carefully considered, refer to BNF (requires internet connection). Where antibiotics are required, it should be noted that many antibiotics interact with coumarins and ideally the INR should be rechecked three days after starting a course of antibiotics, regardless of the length of the antibiotic course.

This is a guide – patients may require higher or lower levels of anticoagulation depending upon their individual risk factors for bleeding or thrombosis.

Indications for oral anticoagulation, target INR and grade of recommendations

For advice on bridging therapy refer to BSH guidelines on the perioperative management of anticoagulation and antiplatelet therapy (requires internet connection).

Management of Warfarin and Direct Oral Anticoagulants (DOACs) in Adult Patients Undergoing Surgery or Invasive Procedures

Recommendations for valve-location-specific target international normalised ratios (INRs)  

^aProsthesis thrombogenicity:

Low = Carbomedics (aortic position), Medtronic Hall, St Jude Medical (without Silzone);

Medium = Bjork-Shiley, other bileaflet valves;      

High = Lillehei-Kaster, Omniscience, Starr-Edwards.

^bPatient-related risk factors: mitral, tricuspid, or pulmonary valve replacement; previous thromboembolism; atrial fibrillation; left atrial diameter >50mm; left atrial dense spontaneous contrast; mitral stenosis of any degree; left ventricular ejection fraction <35%; hypercoagulable state.

Adapted from: The Task Force on the Management of Valvular Heart Disease of the European Society of Cardiology. Guidelines on the management of valvular heart disease. European Heart Journal 2007; 28: 230–268. Guidelines on oral anticoagulation with warfarin – fourth edition BCSH (2011)

Adapted from:

Scottish Intercollegiate Guidelines Network (SIGN) (2013) SIGN Publication No. 129, Antithrombotics: Indications and management. SIGN, Edinburgh.

Guidelines on oral anticoagulation with warfarin – fourth edition, British Committee on Standards in Haematology (2011)

British Medical Association, Royal Pharmaceutical Society of Great Britain (2012) British National Formulary, 66^th edn.

*See guidance for management of haemorrhage with novel oral anticoagulants.