INR Values: Securely in the Safe Range

Cut your finger, put on a bandage, forget it.

A bandage helps to cover a bleeding wound. Stopping the bleeding, however, is mostly the job of our normally well-functioning coagulation system. An intact blood clotting (haemostatic) system ensures that wounds are sealed both on the inside and on the outside.

The blood vessel constricts at the site of the injury and thrombocytes aggregate at the affected location on the vessel wall. This interaction results in a thrombus, which closes the wound. As part of this process, clotting factors are activated, leading to the formation of fibrin to stabilise the thrombus and hold it in place.

Walked past the corner of the table too quickly, bumped into it, got a little bruise – by the next day you’ve forgotten all about it.

Bumping into the edge of an object injures blood vessels. Blood permeates the tissue as a result and coagulates under the skin, producing a bruise, also known as a haematoma. As it breaks down, the haematoma undergoes various colour changes – an indication that the coagulation system is working.

If everything proceeds as described above, the coagulation system is considered to be working properly and can be represented by an INR value of 1.0 (please note: includes the exogenous coagulation system only).

But it’s not that simple for everyone.

When blood fails to clot (coagulate) sufficiently – the most frequent form that haemostatic disorders take – there is a risk of excessive bleeding (haemophilia) and thus of increased blood loss. If haemostasis is excessive, the result is a major risk of thrombosis – of a blood vessel becoming blocked by a clot.

This is always a life-threatening situation. If an individual has a hereditary or acquired condition such as atrial fibrillation/heart rhythm disorders, recurrent thromboses, embolisms, heart attack or implanted artificial heart valves or cardiovascular support systems (“artificial heart”), monitoring haemostasis with appropriate medication is imperative.

The Quick test is used for determining whether the extrinsic coagulation system is working as it should. The Quick value is derived from the quantitative determination of thromboplastin time (TPT). Because Quick values determined at different institutions are often not comparable, the international normalised ratio (INR¹) has become established as a value for measuring blood clotting that can be compared throughout the world. The INR serves as a way of standardising the Quick value.

For patients taking anticoagulants in the vitamin K antagonist family (Marcumar^®, etc.), a POCT system can be used for determining the INR, thereby providing regular information on the status of haemostasis.

Using POCT systems requires correct pretesting in order to ensure that the analysis will not be affected by any external influencing factors. Even tiny interactions, with disinfectants for example, can lead to incorrect results in sample volumes as low as 3 µl.

Depending on the diagnosis, each patient has a target range in which he or she is considered “safe”.

Nevertheless, patients are individuals, and it follows that their medication must be managed personally. INR fluctuates in response to diet, exercise, stress (negative or positive), dietary supplements and much more. Close INR monitoring provides rapid, reliable information on these fluctuations, so that medication can be adjusted quickly in response.

INR measurements are – for reasons of patient safety – generally taken at the treating physician’s clinic. There is, however, a self-management option as well.

Under certain circumstances, patients undergoing permanent or long-term treatment with vitamin K antagonists can learn how to perform INR determinations themselves and dose their medications accordingly.² In addition to willingness on the part of patients to assume responsibility for their own treatment, successful patient management also requires close coordination with the treating physician, of course.

SUMMARY:

Even just the tiniest injury sets the coagulation cascade in motion, which can take a normal length of time (INR¹) or two to three times as long (INR 2 - 3) for bleeding to stop. Achieving the safe, target range with as much certainty as possible is important.

 

¹_{The INR is calculated as the thromboplastin time (TPT) of the patient’s plasma divided by the TPT of normal plasma raised to the power of the international sensitivity index (ISI). This factor describes the sensitivity of the TPT reagent with respect to an international standard.}

²_{Studies such as that by C. Heneghan et al. in The Lancet, 2012, provide evidence that PSM reduces complications and yields a positive value for time in therapeutic range (TTR).}