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INR Testing

Key Messages INR PDF
Introduction
Initiation of warfarin therapy
Monitoring INR
Other issues for INR management
Appendices
References

Initiation of warfarin therapy
Intiation protocols | Pre initiation tests | Detailing the plan | Target INR range
Prescribing warfarin | Use of drug labeling | Patient education

Initiation protocols

In many cases warfarin is initiated in hospitals because of the presence of active clot formation. In this situation warfarin is started in conjunction with heparin because the anticoagulant effect of warfarin does not occur for approximately five days. Also the initial period of treatment with warfarin may be associated with a procoagulant state; heparin provides some protection from the risks related to this.

For outpatients who do not require rapid anticoagulation, for example, patients with stable atrial fibrillation, a low-dose warfarin initiation protocol can be used (NZGG, 2005). Low-dose initiation is safe, achieves therapeutic anticoagulation in the majority of patients within 3 to 4 weeks and reduces the risk of over-anticoagulation. This is particularly useful for elderly patients.

A number of low-dose protocols are available and there is no evidence to favour one over another. However, it is recommended that to avoid confusion all practice members use the same initiation protocol in most circumstances.

The following protocol uses 3 mg daily doses and requires only weekly INR testing. The majority of patients reach a stable dose within one month and in the trial no patient suffered a thrombotic or bleeding complication in the first month (Janes, 2004). An even more cautious approach is needed for patients on amiodarone or other potentiators of warfarin action (appendix 3) and for people with co-morbidities.

The procoagulant state

The anticoagulant effect of warfarin is attained by blocking the activation of the clotting factors VII, IX, X, and II. However, warfarin also has a simultaneous procoagulant effect, caused by blocking the activation of two endogenous anticoagulants, protein C and protein S. Protein C has a short half-life, therefore it is depleted quickly after the initiation of warfarin therapy. Because both proteins C and S are anticoagulants, a rapid depletion of these proteins leads to a transient hypercoagulable state in the first one to two days of warfarin therapy. The use of high loading doses may potentiate this phenomenon.

Vitamin K - dependent clotting factors
Name Function Half-life
Protein C Anticoagulant 8 hours
Protein S Anticoagulant 30 hours
Factor VII Procoagulant 7 hours
Factor IX Procoagulant 24 hours
Factor X Procoagulant 36 hours
Factor II Procoagulant 50 hours

A Low Dose Warfarin Initiation protocol

The guide is only valid if the patient has taken seven days of warfarin before the day 8 INR. If doses have been omitted or the INR is performed early the dose may be seriously overestimated. Due to the high number of biological and other variables inherent in warfarin therapy its use should be augmented by sound clinical judgement.

A low dose protocol for warfarin initiation (Janes, 2004)
  INR Warfarin Daily Dose Notes
Day 1 Obtain Baseline INR 3 mg  
Day 2 - 7   3 mg  
Day 8 < 1.4 6 mg * * follow blue guide for 2nd week
1.4 - 1.5 5 mg  
1.6 - 1.8 4 mg  
1.9 - 2.1 3 mg  
2.2 - 2.5 2.5 mg  
2.6 - 2.7 2 mg  
2.8 - 3.0 Omit 1-2 days, reduce to 1 mg  
> 3.0 Stop Warfarin. Check causes, high INR protocol and need for warfarin. Repeat INR in 3-5 days. Restart at 1 mg if indicated.  
Day 15 Most patients will have received stable doses on day 8 and others will only need minor dose adjustments   When INR is stable extend dosing interval and transfer to maintenance guide.

Guide for patients on 6 mg on days 8 to 14
Day 15 < 1.4   Unusual, check adherence, medication etc. Increase to 10 mg
  1.4 - 1.6 8 mg  
  1.7 - 1.8 7 mg  
  1.9 - 2.4 6 mg  
  2.5 - 2.9 5 mg  
  3.0 - 4.0 4 mg Consider omitting 1-2 days
  4.1 - 5.0 reduce dose by 1-2 mg Omit 2 days, check doses taken
  > 5.0   Check high INR protocol. Check doses taken. Omit 3 days and check INR

An outpatient slow loading regimen was assessed in 200 outpatients requiring anticoagulation for atrial fibrillation. Patients were started on 3 mg of warfarin daily for 1 week and subsequent doses determined by weekly INR measurement. 86% of patients had an INR greater than 2 by day 15 and 58% had reached a stable maintenance dose by day 22 and 85% by day 29. The INR on day 8 was predictive of maintenance dose. Only 11 patients had an INR greater than 4 and no patient suffered a thrombotic or bleeding complication in the first month (Janes, 2004).

High Risk
Transfer of care across the primary – secondary interface

Transfer of care from secondary to primary care may be high risk for several reasons:

  • Poor communication on discharge may leave the primary care clinician with inadequate information to make safe testing and dose adjustment decisions.
  • Patients may be discharged from hospital with tablet strengths, which were used for loading doses but are inappropriate for maintenance therapy.
  • Patients often leave hospital with other medications, e.g. antibiotics, which can interact with warfarin.
  • The maintenance dose is usually much lower then the loading dose given in hospital, and warfarin has a very long half-life, so accumulates leading to over-anticoagulation.

Some New Zealand hospitals have developed protocols for the timely transfer of information about warfarin therapy to primary care on patient discharge. Essential details have been found to be:

  • Condition for which warfarin has been prescribed
  • Target INR range
  • Planned duration of treatment
  • Brand and strength of warfarin tablets given
  • Last three doses
  • Last three INRs
  • Date next INR test due

This information can also be usefully placed in the patient-held anticoagulation record (“The Red book”).

New Zealand hospitals use a variety of warfarin initiation protocols and there is little evidence that one is any better than another. It is probably wise to follow on with the protocol initiated by their local hospital for patients who start warfarin in the hospital environment. This requires primary care clinicians to have copies of local hospital protocols.

Pre initiation tests

Before starting warfarin a baseline INR/PR should be performed together with an APTT, FBC to exclude thrombocytopenia, and liver function tests.

Detailing the plan for anticoagulation therapy in clinical records

Misunderstandings are less likely when standardised methods are used to record the management plan for anticoagulation therapy in the clinical notes. The method chosen will depend on how clinical records are managed locally but there should at least be a standard location within the patient notes for the following information:

  • The patient is on warfarin
  • Condition for which prescribed
  • Target INR range
  • Planned duration of treatment
  • Brand of warfarin

The information that a patient is on warfarin must be immediately obvious to any clinician who accesses the patient’s clinical record. The prescribing alerts on computer systems cannot be relied on because they are often ignored or turned off.

To create an alert, in MedTech, which opens whenever someone accesses the clinical records of someone on warfarin, see appendix 4.

Target INR range

In most situations the INR target range is 2.0 – 3.0. This range is appropriate for the prophylaxis or treatment of venous thromobo-embolism and reduction of the risk of systemic embolism for people with atrial fibrillation, valvular heart disease or following MI (Campbell, 2001). In some situations higher ranges are more appropriate.

Prescribing warfarin

All clinicians caring for an individual should use the same brand of warfarin
Marevan® and Coumarin® are available in New Zealand
Marevan accounts for approximately 95% of prescriptions of warfarin in New Zealand
The brands are not interchangeable and come in different tablet strengths
During community initiation only 1 mg tablets should be used to minimise confusion

Prescribers can use drug labelling to highlight the importance of INR monitoring

The labelling on warfarin medication gives an opportunity to remind patients of the need for regular blood tests. Labels such as “PRN” or “as required” can lead to misunderstandings. A better option may be “Take the dose advised by your doctor or nurse. You need regular INR blood tests to make sure this dose is right for you.”

Patient Education

Patients who are well informed and understand what they are doing are more likely to benefit from treatment; therefore effective patient education is an important component of achieving good INR levels.

Patient education needs to cover at least the following key points:

Need for patient to regularly remind their doctor, pharmacist, dentist or other health professional they are receiving warfarin
Requirement for regular blood tests
Adherence to dosage changes following blood test results
Importance of avoiding other medications (including herbal medicines and supplements) except following discussion with clinician, pharmacist or other healthcare provider
Significance of illness, such as diarrhoea, infection or fever on warfarin use
Ability to recognise the signs of possible bleeding
Bleeding is the most serious potential side effect of warfarin. If patients experience any of the following symptoms, they must call their doctor immediately:
  • Red or dark brown urine
  • Red or black stool
  • Severe headache
  • Unusual weakness
  • Excessive menstrual bleeding
  • Prolonged bleeding from gums or nose
  • Dizziness, trouble breathing or chest pain
  • Unusual pain, swelling or bruising
  • Dark, purplish or mottled fingers or toes
  • Vomiting or coughing up blood

The patient-held record traditionally known as “the red book” facilitates patient education and sharing of information between patients and their clinicians about an individual’s warfarin therapy and INR monitoring.

Patients should always show their red book when they see a clinician or pharmacist, and when they purchase over-the-counter or alternative medicines. Clinicians and pharmacists can encourage this by asking to see the patient-held record whenever they consult with someone they know to be on warfarin.

Patients and health professionals have a joint responsibility to make sure the record is kept up to date.

red book

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