INR

Testing

bpac nz
better medicine
This programme was developed by: Rachael Clarke
Sonia Ross
Dr Trevor Walker
David Woods

With the assistance and guidance of: Dr Sanjeev Chunilal, Haematologist, North Shore Hospital
Avril Lee, Integration Pharmacist, Waitemata District Health Board
Sarah Janes, St Richards Hospital, Chichester, UK

bpacnz clinical advisory group: (laboratory programme)

Tracey Barron
Dr Dave Colquhoun
Michele Cray
Dr Rosemary Ikram
Dr Cam Kyle
Dr Lynn McBain
Dr Allan Moffitt
Professor Murray Tilyard

Developed by bpacnz
Level 8, 10 George Street
PO Box 6032
Dunedin

Phone 03 477 5418

Fax 0800 bpac nz (0800 27 22 69)
Email rachael@bpac.org.nz

www.bpac.org.nz
bpacnz October 2006

All information is intended for use by competent health care professionals and should be utilised in
conjunction with pertinent clinical data.
Contents

Key Messages 4

1. Introduction 5
1a. The role of INR 5

1b. What is INR? 6

1c. Some people are at particular risk from warfarin therapy 6

2. Initiation of warfarin therapy 7

2a. Initiation protocols 7

2b. Pre initiation tests 10

2c. Detailing the plan for anticoagulation therapy in clinical records 10

2d. Target INR range 10

2e. Prescribing warfarin 11

2f. Prescribers can use drug labelling to highlight the importance of INR monitoring 11

2g. Patient Education 11

3. Monitoring INR 13

3a. INR testing schedule 13

3b. Changes in INR levels 14

3c. Managing alterations in the INR 15

3d. What to do when the INR is high 16

3e. Taking a sample for INR testing 17

3f. Questions for the patient when sample taking 17

4. Other issues for INR management 18

4a. Ceasing warfarin therapy 18

4b. Dental extractions and preoperative warfarin doses 18

4c. Warfarin should be avoided in pregnancy 18

4d. Standardised procedures for rest homes 18

4e. Near patient testing 18

5. Appendices 19

1. Guide for using INR to manage warfarin 19

2. Treatment guide for managing warfarin 21

3. Drugs which potentiate the action of warfarin 23

4. Adding an alert for patients on warfarin 24

6. References 25

INR Testing | 
 Key Messages

To ensure safe and effective anticoagulation, a systematic and practice-wide approach

is needed for warfarin therapy and for the maintenance of INR levels within appropriate
target ranges. You can test your practice systems with the bpacnz practice audit for INR
monitoring

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.

Regular testing of INR levels is essential for all people taking warfarin. For most people
once the INR is stable the rate of INR testing can be extended to two weekly and then 4 to
6 weekly. However people with higher levels of risk, may need more frequent testing.

 | INR Testing
1. Introduction
Warfarin is the most widely used anticoagulant in New Zealand. It has a valuable role Good management
in the prevention of thrombosis but the use of warfarin is associated with serious of INR levels
risks. Warfarin is the most frequent cause of adverse drug reactions in New Zealand
requires a
(Didham, 2006).
systematic
approach involving
To ensure safe and effective anticoagulation, a systematic and practice-wide approach
is needed for warfarin therapy and the maintenance of INR levels within appropriate the whole practice
target ranges. team.

1a. The role of INR

INR testing is used to maintain warfarin response within the therapeutic window.
Maintaining the INR within a target range is the key to minimising the risks of bleeding
while providing the benefits of anticoagulation (Blann, 2003).

Therapeutic Window
Thr

Usually INR 2.0 - 3.0

ic
om

ag
bo

rh
or
em

ol
em
b

ic a
H
Clinical events

Intensity of anticoagulation (INR) (Blann, 2003)

INR Testing | 
 1b. What is INR?

The basis of the INR is the one-stage prothrombin time (PT)

using the reagent thromboplastin. In the past, PT values varied

( )
dependent on the particular thromboplastin used. To avoid
this, all thromboplastins are now standardised against a WHO INR = Patient PT ISI

standard, and are assigned an International Sensitivity Index Control PT

(ISI). This enables the International Standardised Ratio (INR) to
be calculated. The development of INR has enabled patients
on warfarin therapy to be managed more effectively as the INR
result is independent of the thromboplastin used and therefore
comparable across all laboratories.

1c. Some people are at particular

risk from warfarin therapy

The large number of biological and other variables involved

means that achieving good control of INR levels is not a simple
task.

There is no standard response to warfarin - some people

are particularly sensitive to the effects of warfarin while
others can be relatively resistant.

Elderly people require lower doses of warfarin to achieve

target INRs and may find attending for regular blood tests
and adhering to complex warfarin regimens difficult.

Poor literacy or numeracy skills are associated with

poorer control of INR levels.

 | INR Testing
2. Initiation of warfarin therapy
2a. 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

Vitamin K - dependent clotting factors
activation of the clotting factors VII, IX, X, and II. However, warfarin
also has a simultaneous procoagulant effect, caused by blocking the Name Function Half-life
activation of two endogenous anticoagulants, protein C and protein Protein C Anticoagulant 8 hours
S. Protein C has a short half-life, therefore it is depleted quickly after Protein S Anticoagulant 30 hours

the initiation of warfarin therapy. Because both proteins C and S are Factor VII Procoagulant 7 hours

anticoagulants, a rapid depletion of these proteins leads to a transient Factor IX Procoagulant 24 hours

hypercoagulable state in the first one to two days of warfarin therapy. Factor X Procoagulant 36 hours
Factor II Procoagulant 50 hours
The use of high loading doses may potentiate this phenomenon.
Regal, 2004

INR Testing | 
 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
* follow blue guide for
< 1.4 6 mg *
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
Day 8 2.6 - 2.7 2 mg
2.8 - 3.0 Omit 1-2 days, reduce to 1 mg
Stop Warfarin. Check
causes, high INR protocol and
> 3.0 need for warfarin. Repeat INR
in 3-5 days. Restart at 1 mg if
indicated.
Most patients will have
When INR is stable
received stable doses
extend dosing interval
Day 15 on day 8 and others will
and transfer to
only need minor dose
maintenance guide.
adjustments

Guide for patients on 6 mg on days 8 to 14

Unusual, check
Day 15 < 1.4 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
Consider omitting 1-2
3.0 - 4.0 4 mg
days
Omit 2 days, check
4.1 - 5.0 reduce dose by 1-2 mg
doses taken
Check high INR protocol.
Check doses taken.
> 5.0
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).

 | INR Testing
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.

INR Testing | 
 2b. 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.

2c. Detailing the plan for anticoagulation

therapy in clinical records

Misunderstandings are less likely when standardised methods are used to record To create an alert,
the management plan for anticoagulation therapy in the clinical notes. The method in MedTech, which
chosen will depend on how clinical records are managed locally but there should at
opens whenever
least be a standard location within the patient notes for the following information:
someone accesses
the clinical records
The patient is on warfarin of someone on
Condition for which prescribed warfarin, see
appendix 4.
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 patients clinical record. The prescribing alerts on
computer systems cannot be relied on because they are often ignored or turned
off.

2d. Target INR range

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

10 | INR Testing
2e. 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

2f. 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.

2g. 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

INR Testing | 11
 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 Prolonged bleeding from gums or nose

Red or black stool Dizziness, trouble breathing or chest pain

Severe headache Unusual pain, swelling or bruising

Unusual weakness Dark, purplish or mottled fingers or toes

Excessive menstrual bleeding Vomiting or coughing up blood

The patient-held record traditionally

Patient Handbook
known as the red book facilitates
patient education and sharing of
information between patients and their Your
clinicians about an individuals warfarin
therapy and INR monitoring.
anticoagulant
treatment
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 CARRY THIS BOOKLET
WITH YOU AT ALL TIMES
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.

12 | INR Testing
3. Monitoring INR

3a. INR testing schedule

Regular testing of INR levels is essential for all people taking warfarin. The A reasonable standard for
first three months have the highest rate of major bleeding (approximately good control of warfarin
2%). The rate falls significantly after this. For most people once the INR is
therapy is an INR within the
stable the rate of INR testing can be extended to two weekly and then 4 to 6
target range 60% of the
weekly. However people with higher levels of risk, may need more frequent
time (Machin, 2002).
testing.

The INR is generally considered stable when two or more consecutive Comments from our UK reviewer:
tests, performed at least 24 hours apart are within the target range. We have shown INR interval can
be extended out to 14 weeks in
Some fluctuation of the INR within the target range is to be expected
stable patients. Certainly lots of
and adjustment of the dose is not required. Wide variations within the
our patients are at 8-12 weeks.
range over a few days may be more significant (BC Health Services, S Janes.
2004). (Lidstone, 2000)

For patients initiated with low-dose protocol (warfarin

initial dose 2 3mg daily):

Initially When INR < 4: Weekly Until stable for 2
When INR > 4: Every 2-3 days consecutive tests
Then: Fortnightly Until stable for 2 - 3
consecutive tests
Maintenance:
Most patients can be extended to 4 - 6 weekly testing
however a minority may require more frequent testing.

(Adapted from Janes, 2004)

For patients initiated with higher doses:

Initially daily for at least five days Until stable for 2

consecutive tests
Then: every 3 - 5 days Until stable for 2
consecutive tests
Then: weekly Until stable for 2 - 3
consecutive tests
Then: fortnightly Until stable for 2 - 3
consecutive tests
Maintenance: Most patients can be extended to 4-6 weekly testing
however a minority may require more frequent testing
(Adapted from Horton, 1999)

INR Testing | 13
 3b Changes in INR levels

Changes in the INR level in a usually stable patient may be due to a number of reasons:

Non adherence to dosage regimen

Drug interactions (pharmaceutical or herbal)

Major changes in diet or alcohol intake

Systemic or concurrent disease

Unknown causes

Non adherence to dosage regimen

An erratic INR may reflect non-adherence to the drug regimen often due to misunderstandings of
dosage requirements. A missed dose of warfarin is usually reflected in the INR result 2 to 5 days
after the missed dose (Jaffer, 2003), although a response may be seen within 16 hours (National
Guideline Clearinghouse, 2006).

Drug interactions

Almost any drug can interact with warfarin; effects are more marked when starting, changing or
stopping the dose.

For short courses of a new drug therapy, dose Check INR one week after
adjustment is not essential. If a known potentiator is
commencement of a new
prescribed (appendix 3), a slight dose reduction or
medication.
omission of one warfarin dose may be recommended.

If medication is taken for more than five days, check INR one week after commencement. Similar
precautions need to be taken when discontinuing or changing doses of a medication. Information
on warfarin drug interactions can be found in resources such as your practice management
system, MIMs and BNF.

The use of herbal medicines is gaining in popularity, and the number of studies performed on
the interactions with warfarin is rather limited. Therefore, it is prudent to assume any herbal
medication may have the potential to alter the INR.

Diet

Patients on warfarin are usually advised to consume a reasonably consistent proportion of vitamin
K rich foods. This is probably most relevant in patients who have had markedly reduced food intake
because of illness, hospitalisation, travel and fad diets (Campbell, 2001). A recent study suggests
that the role of excessive dietary vitamin K may have been overstated, with the exception of
natto (Japanese fermented soybean) which causes a marked and prolonged inhibition of warfarin
(Schurgers, 2004).

14 | INR Testing
Systemic or concurrent disease

Many systemic diseases can influence INR results:

Congestive heart failure: may cause hepatic congestion of blood flow and inhibit warfarin metabolism, this may be
particularly troublesome during exacerbations of heart failure.

Hypothyroidism: decreased catabolism of vitamin K clotting factors may decrease INR values.

Hyperthyroidism: conversely, hyperthyroidism may increase catabolism of vitamin K clotting factors and increase INR
values.

Liver failure: may cause elevation of INR due to reduced production of clotting factors.

Other illnesses: other intermittent conditions such as fever, vomiting and diarrhoea may affect the INR; ill patients may
also reduce their usual dietary intake.

Unknown causes

In many cases, no explanation may be found for unstable INR values. It may be worthwhile discussing aspects of the dosing
regimen. Changes in the INR may also be the result of occult causes, such as undisclosed drug use, lifestyle and medical
causes.

3c. Managing alterations in the INR

If the fluctuation is minor, changes in weekly doses are usually not required, but a Use a standard guide to
cause should be sought. For more significant fluctuations use of a standard guide assist dose modification
reduces the risk of confusion.
There are many guides on dosage adjustment for people on warfarin therapy; there is no evidence to favour one over
another. A guide from the British Columbia Health Service is reproduced below.

Dosage Adjustments for Patients on Warfarin Maintenance

Therapy, Target 2.0 - 3.0
INR Dosage Adjustment Changes in warfarin dosage

Increase weekly dose by 20% and give one time top-up may take several days to
< 1.5
additional amount equal to 20% of weekly dose affect INR. Hence, frequent
1.5 - 1.9 Increase weekly dose by 10% dosage adjustment (<4-5 days
2.0 - 3.0 No change interval) is not recommended.
No change - recheck in one week. If persistent, decrease
3.1 - 3.9 Adjustments may need to be
weekly dose by 10-20%
modified in the presence of
Omit 1 dose; decrease weekly dose by 10-20% and
4.0 - 5.0 intercurrent illness.
recheck in 2-5 days

See guide for Treatment of Patients Overanticoagulated

> 5.0
with Warfarin (see section 3d)

INR Testing | 15
 3d. What to do when the INR is high (BC Health Services)

Guideline for Over Anticoagulation

Clinical Guideline

1. Stop warfarin
INR 5 - 8 without bleeding 2. Test INR daily until stable
3. Restart in reduced dose when INR < 5
4. Give vitamin K 0.5 - 1 mg oral/sc, if INR fails to fall, or
if there is high risk of serious bleeding

5. Stop warfarin
INR > 8 with minor bleeding 6. Consider admission if clinically appropriate
7. Test INR daily until stable
8. Restart in reduced dose when INR < 5
9. Give Vitamin K 1-2 mg oral/sc

10. Stop warfarin

High INR and major bleeding 11. Give Vitamin K 10 mg sc
12. Admit stat

16 | INR Testing
3e. Taking a sample for INR testing

There are no special requirements for the patient prior to collection of blood for INR testing. There is
no particular time at which INRs should be collected, but often a time will be recommended that fits
into the practice routine. Having the specimen collected on the same day of the week may help with
continuity of care as the same practice staff are likely to be on duty.

Blood specimens for INR should be collected into a tube (usually light blue top) containing sodium
citrate. The ratio of blood to anticoagulant is important therefore the tube must be filled to the fill
mark on the tube.

At the time of collection it is good practice to view the patient handbook, and use this as an opportunity
to ask questions specific to the patients warfarin control.

3f. Questions for the patient when sample taking

Some practices may elect to take blood for INR testing at the surgery rather than sending patients
to the laboratory. This gives an opportunity for ongoing patient education and information sharing.
Practice nurses have told us they usually discuss adherence to the dosing regimen, changes to
medication, major changes in diet and signs of bleeding. They always sight the patient-held record
and make sure it is up to date.

As a result of this discussion with the patient any additional notes can be added to the laboratory
form. Significant notes may include changes in warfarin dose, or significant changes in diet or
addition of new medications.

INR Testing | 17
4. Other issues for INR management

4a. Ceasing warfarin therapy

Warfarin therapy can be discontinued abruptly when the duration of treatment is completed. Prospective studies have
not indicated a rebound prothrombotic state and there is no need for gradual withdrawal.

4b. Dental extractions and preoperative warfarin doses

For minor surgical procedures, the warfarin dose should be stopped or adjusted to achieve a target INR of approximately
2.0 on the day of surgery. For major surgery, warfarin should be stopped at least three days prior to surgery; further
actions will depend on resulting INR levels and the thrombotic risk of the condition for which the patient is receiving
anticoagulation.
Anticoagulation does not need to be stopped for dental extraction for patients with an INR less than 3.0.

4c. Warfarin should be avoided in pregnancy

Pregnant women should never take warfarin, as it is teratogenic (Medsafe, 2002). Women of child-bearing age on
warfarin should be using effective contraception and contact their doctor urgently (by six weeks) if they think they are
pregnant.

4d. Standardised procedures for rest homes

The establishment of a systematic approach to the use of warfarin is particularly important in rest homes. There are
often several health professionals involved in the prescribing, dose adjustment and administration of warfarin. It is
essential that there are robust systems in place to guide the processes.

Clear written instructions are necessary to guide rest home staff. Verbal instructions on warfarin therapy in rest homes,
for example on changing doses, are fraught with risk and should be avoided whenever possible.

4e. Near patient testing

Near patient testing of INR levels is effective for selected patients. There are risks if patients are not well motivated, or
do not fully understand the process, or if quality assurance procedures are not of a high standard.

If you would like to check your current system for maintenance of INR levels you could use bpacs audit, Practice
audit of the systematic management of INR levels, which has been sent to every practice and is available from
www.bpac.org.nz

18 | INR Testing
 Guide for using INR to manage warfarin bpac nz
better medicine

A low dose protocol for warfarin initiation (Janes, 2004) Guideline for Over
INR Warfarin Daily Dose Notes Anticoagulation
Day 1 Obtain Baseline INR 3 mg
Day 2 - 7 3 mg
INR 5 - 8 without bleeding
* follow blue guide
< 1.4 6 mg *
for 2nd week 1. Stop warfarin
1.4 - 1.5 5 mg 2. Test INR daily until stable
1.6 - 1.8 4 mg
3. Restart in reduced dose
1.9 - 2.1 3 mg
when INR < 5
2.2 - 2.5 2.5 mg
Day 8 4. Give vitamin K 0.5 - 1 mg
2.6 - 2.7 2 mg
oral/sc if INR fails to fall, or
2.8 - 3.0 Omit 1-2 days, reduce to 1 mg if there is high risk of serious
Stop Warfarin. Check causes, bleeding
high INR protocol and need
> 3.0 for warfarin. Repeat INR in
3-5 days. Restart at 1 mg if
indicated.
INR > 8 with minor
When INR is
Most patients will have bleeding
stable extend
received stable doses
dosing interval 5. Stop warfarin
Day 15 on day 8 and others
and transfer to
will only need minor 6. Consider admission if
maintenance
dose adjustments clinically appropriate
guide.
7. Test INR daily until stable
Guide for patients on 6 mg on days 8 to 14
8. Restart in reduced dose
Unusual, check when INR < 5
adherence
Day 15 < 1.4 9. Give Vitamin K 1-2 mg
medication etc.
oral/sc
Increase to 10mg
1.4 - 1.6 8 mg
1.7 - 1.8 7 mg
1.9 - 2.4 6 mg High INR and major
2.5 - 2.9 5 mg bleeding
Consider omitting
3.0 - 4.0 4 mg 10. Stop warfarin
1-2 days
Omit 2 days, 11. Give Vitamin K 10 mg sc
4.1 - 5.0 reduce dose by 1-2 mg check doses
12. Admit stat
taken
Check high INR
protocol. Check
> 5.0 doses taken.
Omit 3 days and
check INR
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.

Dosage Adjustments for Patients on Warfarin Maintenance Therapy, Target 2.0 - 3.0
INR Dosage Adjustment

< 1.5 Increase weekly dose by 20% and give one time top-up additional amount equal to 20% of weekly dose
1.5 - 1.9 Increase weekly dose by 10%
2.0 - 3.0 No change
3.1 - 3.9 No change - recheck in one week. If persistent, decrease weekly dose by 10-20%
4.0 - 5.0 Omit 1 dose; decrease weekly dose by 10-20% and recheck in 2-5 days

> 5.0 See guide for Treatment of Patients Overanticoagulated with Warfarin (see section 3d)
Treatment Guide for managing Warfarin
bpac nz
better medicine

INR testing frequency

The INR is generally considered stable when two or more consecutive tests, performed at least 24 hours apart are within
the target range

Some fluctuation of the INR within the target range is to be expected and adjustment of the dose is not required but wide
variations within the range over a few days may be more significant.

For patients initiated with low-dose protocol (warfarin initial For patients initiated with higher doses:
dose 2 -3 mg):
When INR < 4: Weekly Until stable for Initially Daily for at least Until stable for 2
Initially When INR > 4: Every 2-3 2 consecutive five days consecutive tests
days tests Then: every 3 - 5 days Until stable for 2
Until stable for consecutive tests
Then: Fortnightly 2 consecutive Then: weekly Until stable for 2 - 3

tests consecutive tests

Then: fortnightly Until stable for 2 - 3

Most patients can be extended to 4-6 weekly consecutive tests

Maintenance: testing however a minority may require more Maintenance: Most patients can be extended to 4-6 weekly

frequent testing testing however a minority may require more

frequent testing

Patient education needs to cover at least the

Specimen Collection:
following key points:

Need for patient to regularly remind their doctor, pharmacist, Blood specimens should be collected into a
dentist or other health professional they are receiving warfarin light blue top tube
The tube must be filled completely
Requirement for regular blood tests
View the patient handbook

Adherence to dosage changes following blood test results Ask questions specific to warfarin control, for
example:
Importance of avoiding other medications (including herbal
- Adherence to the dosing regimen
medicines and supplements) except following discussion with
- Any changes in diet
clinician, pharmacist or other healthcare provider
- Any medications the patients may have

Significance of illness, such as diarrhoea, infection or fever on stopped or started

warfarin use - Signs of bleeding

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 Excessive menstrual bleeding Unusual pain, swelling or bruising

Red or black stool Prolonged bleeding from gums or nose Dark, purplish or mottled fingers or toes

Unusual weakness, Severe headache Dizziness, trouble breathing or chest pain Vomiting or coughing up blood

INR Testing | 21
Appendix 3 Drugs which potentiate the action of warfarin

Drugs which potentiate the action of warfarin

Antibiotics Anti-inflammatory Cardiac Gastrointestinal Psychiatric Other

Cotrimoxazole NSAIDs Amiodarone Omeprazole Paroxetine Tramadol

Erythromycin COX II inhibitors Propranolol Cimetidine Fluoxetine Phenytoin
Norfloxacin Sulfinpyrazone Clofibrate Citalopram Tamoxifen
Roxsithromycin Salicylates
Cephalosporin Paracetamol
Ciprofloxacin
Azithromycin
Fluconazole
Miconazole
(including gel)
Metronidazole
Isoniazid

INR Testing | 23
Appendix 4. Adding an alert for patients on warfarin

An alert which appears

To set up an alert to use for patients on warfarin
whenever the clinical
records of a patient on
1. From the menu select: Setup > Patient Register > Alert warfarin are accessed.

2. Put a code, perhaps warf, in the appropriate box and put On Warfarin in the
For use with MedTech.
description box.

3. Click OK, your alert is now set up for use.

To use the warfarin alert for a particular patient

1. When the patients clinical records are open

2. From the menu select: Module > Alerts

3. Click on the box in the window that opens to assign a new alert to the patient

4. In the code box enter warf or whatever code you used.

5. In the text box underneath put details of:

Condition for which patient is on warfarin

Date therapy started

Planned duration of treatment

Target INR

Note: you cannot use the enter key when you are in this text box.

6. Tick the box labelled Auto Prompt Alert

7. Click OK, your alert should now open whenever the patients clinical records are accessed.

24 | INR Testing
References

BC Health Services, British Columba Medical Association. Initiation and Maintenance of Warfarin Therapy, 2004.
http://www.healthservices.gov.bc.ca/msp/protoguides/gps/warfarin_therapy.pdf (accessed 22 September 2006).

Blann AD, Fitzmaurice DA, Lip GYH. Anticoagulation in hospitals and general practice. BMJ 2003;326:153-6.

Campbell P et al. Managing warfarin therapy in the community. Aust Prescr 2001;24:86-9.

Didham R. Hospital admissions for adverse drug reactions. bpacnz internal report 2006.

Horton J, Bushwick B. Warfarin therapy: evolving strategies in anticoagulation. Am Fam Physician 1999;59:635-46.

Jaffer A, Bragg L. Practical tips for warfarin dosing and monitoring. Cleve Clin J Med 2003;70:361-71.

Janes S, Challis R, Fisher F. Safe introduction of warfarin for thrombotic prophylaxis in atrial fibrillation requiring only a
weekly INR. Clin Lab Haematol 2004;26:43-7.

Lidstone V, Janes S, Stross P. INR: intervals of measurement can safely extend to 14 weeks. Clin Lab Haematol
2000;22:291-3.

Machin SJ. Medico legal problems associated with oral anticoagulant services. In oral anticoagulation management
and stroke prevention: the primary care perspective. Editors: D A Fitzmaurice and E T Murray. Newmarket Medical
Communications. 2002;50-57.

Medsafe, Consumer Medicine Information, 2002. http://www.medsafe.govt.nz/Consumers/cmi/m/Marevan.htm

(accessed 22 September 2006).

National Guideline Clearinghouse. Anticoagulation therapy supplement, 2006. http://www.guideline.gov/summary/

summary.aspx?doc_id=9273 (accessed 22 September 2006).

NZGG. The management of People with Atrial Fibrillation and Flutter, 2005. http://www.nzgg.org.nz/guidelines/0085/
AF_Full_Guide_(final).pdf (accessed 22 September 2006).

Regal R, Tsui V. Optimal Understanding of Warfarin: Beyond the Nomogram. P&T 2004;29:652-9.

Schurgers L J et al. Effect of vitamin K intake on the stability of oral anticoagulant treatment: doseresponse relationships
in healthy subjects. Blood 2004;104:2682-9.

INR Testing | 25
26 | INR Testing
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