Management of Elevated INRs

If the INR is greatly above (upwards of for a patient with no risk factors for falls or haemorrhage), or the patient is elderly and at risk of a fall, 1–2mg of IV phytomenadione may be considered.

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INR is a measure of the clotting ability of your blood. Because the clotting ability of blood will vary depending on temperature and humidity etc. a pair of tests that produces something called the INR (International Normalized Ratio) is calculated.

Minor bleeding would include patients who present with bruising or epistaxis of limited duration. Anticoagulated patients who are experiencing minor bleeding should have their warfarin doses omitted and be given 2mg of oral phytomenadione. If the patient has a significantly high INR above 8. Major bleeding can be subdivided into two categories. First is haemorrhage that poses a risk to life, limb or sight. This includes intracranial, retroperitoneal, intraocular, pericardial and muscular bleeding.

Second is haemorrhage that does not cause major haemodynamic compromise ie, a substantial drop in blood pressure , hence is not life-, limb- or sight-threatening. Examples of this include some GI bleeds or continuous epistaxis. The aim of treatment should be to arrest the haemorrhage as quickly as possible and stabilise the patient, thereby limiting further harm.

The risk of warfarin resistance is less relevant in this situation but must still be considered, particularly for patients at major risk of thrombosis eg, those with a major thrombophilia or recipients of older heart valve prosthetics. PCCs are concentrates of specific amounts of vitamin K-dependent clotting factors obtained from pooled plasma products. Beriplex, for example, contains therapeutic levels of all four of these factors. Other products contain only three of these factors.

PCCs are recommended for major bleeding that is life-, sight- and limb-threatening. They are particularly useful for treating patients with intracranial haemorrhage. The outcomes for such patients are likely to worsen as the volume of the original bleed and size of the haematoma increase.

Drawbacks of PCC include its high cost and its potential for causing infection with unknown pathogens — despite being treated for virus inactivation. PCC can be thrombogenic and, in particular, can cause disseminated intravascular coagulation see Box below. However, this is less of an issue for patients who have been excessively anticoagulated.

Disseminated intravascular coagulopathy is the widespread formation of numerous thrombi in response to a variety of conditions, such as shock or trauma. This results in a reduced ability to form further clots and, therefore, can cause uncontrolled bleeding from, for example, the digestive tract, respiratory tract and any skin wounds. Treatment of this condition varies depending on its underlying cause.

PCC must be administered with 5mg of IV phytomenadione. This restores the ability of the body to manufacture vitamin K-dependent clotting factors, allowing the reduction in INR generated by PCC to be maintained. FFP is the supernatant obtained after a unit of blood has been centrifuged. Traditionally, it has been the treatment of choice for patients who are bleeding due to over-anticoagulation with warfarin. However, due to issues that limit its suitability, it is no longer used as widely as previously.

Since FFP is a blood product, it presents the same infection transmission risks as any blood transfusion. This risk can be limited by using FFP that has been treated with methylene blue or solvent detergent.

However, treated FFP tends to only be used routinely in patients under the age of 16 years — presumably due to its increased cost. The content of vitamin K-dependent clotting factors within FFP products is variable. Some evidence suggests that, by using these products, it can be difficult to achieve a sufficient level of Factor IX to induce haemostasis. FFP is generally not suitable for use in patients who are overloaded with fluid. Also, FFP cannot be administered as rapidly as PCC, so it is less likely to be used when a coagulopathy needs to be corrected speedily.

Despite these limitations, FFP continues to be widely used for excessive anticoagulation in many areas of the UK and other countries. This is possibly due to its low cost and the limited availability of PCC. The results of two studies 5,6 suggest that FFP could be used for major bleeding without haemodynamic compromise that is not life-, limb- or sight-threatening.

This advice is echoed by the Northern Regional Haematologists Group. FFP must also be administered with 5mg of IV phytomenadione to ensure the production of endogenous vitamin K-dependent clotting factors. Articles in the series have been commissioned from independent authors who have summarised useful clinical skills. You can use the following forms to record your learning and action points from this article from Pharmaceutical Journal Publications.

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If your learning was planned in advance, please click: If your learning was spontaneous, please click: British Journal of Haematology ; Guidelines on oral anticoagulation: A comparison of the efficacy and rate of response to oral and intravenous Vitamin K in reversal of over-anticoagulation with warfarin. Emergency oral anticoagulant reversal: Clinical experience with the use of clotting factor concentrates in oral anticoagulation reversal.

Clinical and Laboratory Haematology ; Clinical Pharmacist , Vol. For commenting, please login or register as a user and agree to our Community Guidelines. You will be re-directed back to this page where you will have the ability to comment. Pharmaceutics — Dosage Form and Design removes the complexity from the major dosage forms that are commonly encountered by pharmacists in professional practice.

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