- Introduction to blood clotting
- What is the INR?
- Why do we monitor the INR?
- How often do we measure the INR?
- What can interfere with the INR?
- What should my INR be?
- How is INR tested?
Coagulation or blood clotting is a protective mechanism of the body against bleeding. When damage occurs to a blood vessel, a series of reactions take place involving substances found in the blood known as clotting factors. They are called this because they contribute to the formation of a blood clot.
|For more information, see Blood Function and Composition.|
Normally, clotting only occurs when there is blood loss from a damaged blood vessel. However, there are several conditions that can cause blood clots to form in the absence of active bleeding. When this occurs, a person may be at an increased risk of thromboembolic disease. In thromboembolic disease, fragments of blood clots dislodge and circulate in the blood, potentially obstructing blood vessels in the lungs and causing pulmonary embolism, or vessels in the heart and causing heart attack, or in the brain and causing stroke. These conditions are all potentially fatal. Therefore, when a person is at high risk of one of the above conditions (e.g. because they have had a stroke or heart attack previously), anticoagulants (medicines which thin the blood and reduce the formation of clots), are used to minimise the risk of blood clots forming.
People who require long-term anticoagulant therapy are usually given warfarin, an anticoagulant that can be taken in the form of a tablet instead of injection. This is often referred to as oral anti-coagulant therapy.
|For more information, see Anticoagulants.|
The international normalised ratio (INR) is a laboratory measurement of how long it takes blood to form a clot. It is used to determine the effects of oral anticoagulants on the clotting system.
Devised in 1983, the INR provides a standardised method of reporting the effects of an oral anticoagulant such as warfarin on blood clotting. Prior to this, the effects of warfarin on blood clotting were determined by a laboratory measure known as prothrombin time. Measurement of prothrombin time has its advantages, including that it is cheap and simple to perform. However, the disadvantage of this measure is that there can be large differences in the values obtained, depending on which laboratory the value was obtained from – different commercial measuring systems can produce different results. Therefore it is impossible to compare results that come from different laboratories.
In an attempt to overcome the variability between laboratories, prothrombin times were initially expressed as a ratio of the prothrombin time of a control value. The control value was the average of prothrombin times from 20 or more healthy subjects. While expressing prothrombin times compared to a control value was seen as an improvement, it was still insufficient. So in 1983, the international sensitivity index (ISI), was applied to this ratio to derive the INR:
INR = (prothrombintest / prothrombincontrol)ISI
The ISI is a numerical value representing the responsiveness of any given commercial system relative to the international standard. It takes into account the variability in results obtained using different commercial systems in calculating the result. In this way, results from different laboratories and countries can be compared more readily.
We regularly monitor the INR of people using warfarin in order to balance the risk of excessive bleeding (when the INR is too high, meaning that the blood is too thin) against the risk of clotting or thrombosis (when the INR is too low or the blood is too thick). INR values over 4.5 increase the risk of major haemorrhage (bleeding), and an INR less than 2 increases the risk of thromboembolism (formation of blood clots within the blood vessels) and associated conditions such as heart attack and stroke.
Regular monitoring is important with a drug such as warfarin because:
- There is a very small difference between the lowest dose that gives a good effect and the highest dose before side effects (which may be serious) are experienced;
- The doses used by different individuals to achieve the same effect can be highly variable;
- Several drugs interact with the medication to either increase or decrease its effectiveness; and
- What a person eats can also affect the action of warfarin and either increase or decrease its effectiveness.
Evidence suggests that more frequent testing will result in more time within the desired INR target range. For example, studies suggest that the desired results are achieved 50% of the time with monthly monitoring, compared to 85% of the time with weekly monitoring.
On initiation of warfarin therapy, monitoring of prothrombin time/INR occurs on a daily basis until the target INR has been achieved and maintained for at least two consecutive days. Monitoring then occurs every 2–3 days for the next few weeks, and then with decreasing frequency depending on the stability of the results. If the INR remains stable, testing can be spread as far apart as every four weeks. However, as mentioned above, more frequent testing allows for more frequent dose adjustment, and means a person’s INR is more likely to stay within the therapeutic range.
Many medications, foods and even concurrent illness are known to interact with warfarin and therefore interfere with the INR. These affect the way warfarin is processed by the body. Therefore, you should consult your doctor if you:
- Have a sudden change of diet (leafy greens in particular);
- Are taking diet supplementation;
- Are unwell; or
- Are taking other medications, including over-the-counter medications.
Common medications that interfere with warfarin include:
- Many antibiotics;
- Some heart medications, such as amiodarone (e.g. Aratac, Cardinorm), diltiazem (e.g. Cardizem, Diltahexal) and propranolol (e.g. Deralin, Inderal);
- Some anti-cholesterol medications, such as simvastatin (e.g. Lipex, Zocor);
- Some pain relievers and anti-inflammatories, such as celecoxib (Celebrex) and tramadol (e.g. Tramal, Zydol);
- Some antidepressants, such as citalopram (e.g. Cipramil) and sertraline (Zoloft); and
- Some antiepileptics, such as carbamazepine (e.g. Tegretol).
The desired INR depends on the reason why you need anticoagulation. The three most common reasons for warfarin use, along with their target INRs, include:
- Atrial fibrillation: Target INR range 2.0–3.0;
- Venous thromboembolism: Target INR range 2.0–3.0; and
- Prosthetic heart valves: Target INR range varies between 2.0 and 3.5, depending on the type of valve replacement and the presence of any other risk factors.
INR can be monitored either by laboratory blood testing or by using a portable monitoring device.
Laboratory blood testing is the traditional practice in Australia. Blood is drawn from a vein, typically by a GP, and sent to the laboratory for testing. There is a time delay before results are returned to the GP, who analyses the need for dose adjustment with the help of computerised algorithms. The practitioner will then let you know whether a dose adjustment is needed. A dose adjustment will be required if your INR value for the test is outside the therapeutic range (too high or too low). As follow up is typically done by telephone, you need to take extra care that you understand and precisely follow your doctor’s instructions.
Portable devices, introduced in the 1990s, allow you, your doctor or another health practitioner (e.g. pharmacist or nurse) to obtain blood test results on the spot, using a drop of fingertip blood as the sample. The blood drop is placed on a test strip which is inserted into the portable device so that the clotting time can be measured. The result as an INR value is then displayed on the device’s screen.
These devices have been demonstrated accurate and reliable and to provide reproducible results which are similar to those obtained through laboratory testing.
Portable devices can be used to measure blood INR either:
- In a health facility; or
- In your home.
If the device is used for monitoring in a health facility, a health practitioner (often a nurse) conducts the blood test and records the result on your behalf. In consultation with the doctor prescribing warfarin or based on a computerised algorithm, the health practitioner can notify you immediately if any dose adjustments are necessary.
Benefits have been associated with this testing method. In particular, obtaining on the spot results enables better management of oral anti-coagulation therapy, as dose adjustments can be made immediately and discussed with the health practitioner face to face rather than over the phone. Some people also prefer not needing to have blood drawn from a vein using a needle with this method.
When a portable device is used for home monitoring, you usually conduct the test yourself. However, in some countries health practitioners can visit you in your homes or aged care settings to conduct blood monitoring. This enables you to have your INR monitored without the inconvenience of attending a healthcare facility.
If you self-test, there are two options available:
- Self-monitoring: which involves your testing your INR at home, and then phoning a clinic with the result and to find if there is a need to adjust the dose and if so what the dose adjustment is; or
- Self-management: which involves you testing your INR at home, and adjusting your oral anticoagulant dose based on the result obtained, according to a pre-determined dose INR schedule.
If you monitor your INR at home, you’ll need to be trained in the following areas:
- Preventing complications (i.e. maintaining the INR within the therapeutic window); and
- Effect of diet and medications on INR values.
Self-monitoring is considered the gold standard of care, as it has been found that individuals using this method remain within therapeutic range over 70% of the time. Self-testing has the advantage of being more convenient and making it easier for you to take the correct dose of warfarin at the correct time. People who use this method are more likely to monitor their INR more frequently. They are also less likely to experience blood clot or bleeding complications. Compared to laboratory testing, self-monitoring and self-management are associated with a 50% reduction in thromboembolic events such as stroke and heart attack, an overall reduction in death from any cause, and a small reduction in major bleeding.
These reductions may be the result of people who self-test spending more time within the therapeutic range, due to more frequent monitoring and more timely dose adjustments. On the spot results enable immediate adjustments to the warfarin dose. It may also be particularly beneficial for individuals who need to travel long distances to attend a clinic for laboratory blood testing.
There are, however, some limitations with this model of INR monitoring. It can cause some individuals to become more anxious about their health and in these people, without proper support and supervision from a health professional, their INR regulation may be poorer.
It’s also important to realise that self-monitoring is not appropriate for or desirable to all people. In one study, 68% of people either could not or would not take part in self-monitoring/self-management of their INR. Of those people who did agree and attempted INR self-monitoring, 24.9% were unable to complete the task. The main reasons for this included physical limitations, problems attending training sessions, failing training assessments, and problems with the device.
While self-monitoring/self-management may provide positive benefits, including more time spent in the therapeutic range and fewer complications of warfarin therapy, you’ll need to talk to your doctor about whether or not it is a suitable monitoring method for you.
|For more information on coagulation, including information on anticoagulants, blood coagulation tests and test devices, see Blood Clotting and Monitoring.|
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Drugs related to this investigation: