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INR Testing

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

Monitoring INR
INR testing schedule | Changes in INR levels | Managing alterations
When INR is high | Taking a sample | Questions for the patient

INR testing schedule

Regular testing of INR levels is essential for all people taking warfarin. The first three months have the highest rate of major bleeding (approximately 2%). The rate falls significantly after this. 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.

  • 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. Wide variations within the range over a few days may be more significant (BC Health Services, 2004).

For patients initiated with low-dose protocol (warfarin initial dose 2 - 3mg daily):
Initially When INR < 4: Weekly
When INR > 4: Every 2 - 3 days
Until stable for 2 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)

A reasonable standard for good control of warfarin therapy is an INR within the target range 60% of the time (Machin, 2002).

Comments from our UK reviewer:
“We have shown INR interval can be extended out to 14 weeks in stable patients. Certainly lots of our patients are at 8-12 weeks”.
S Janes.
(Lidstone, 2000)

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.

Check INR one week after commencement of a new medication.

For short courses of a new drug therapy, dose adjustment is not essential. If a known potentiator is prescribed (appendix 3), a slight dose reduction or 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).

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.

Managing alterations in the INR

Use a standard guide to assist dose modification

If the fluctuation is minor, changes in weekly doses are usually not required, but a cause should be sought. For more significant fluctuations use of a standard guide 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
  • Changes in warfarin dosage may take several days to affect INR. Hence, frequent dosage adjustment (<4-5 days interval) is not recommended.
  • Adjustments may need to be modified in the presence of intercurrent illness.
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)

What to do when the INR is high (BC Health Services)

Guideline for Over Anticoagulation
Clinical Guideline

INR 5 - 8 without bleeding
  1. Stop warfarin
  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

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

High INR and major bleeding
  1. Stop warfarin
  2. Give Vitamin K 10 mg sc
  3. Admit stat

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 patient’s warfarin control.

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.


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