International Normalised Ratio (INR)
March 4th, 2023
Overview
The prothrombin time (PT) and international normalised ratio (INR) are measures of the extrinsic coagulation pathway.
Normal Range
- Prothrombin time - 11 - 15 sec
- INR - 0.9 - 1.3
Important Lab Points
- Collected in a sodium citrate tube to prevent coagulation prior to testing.
- Performed by adding calcium and thromboplastin to a plasma sample and measuring the time to clot.
- Tests the extrinsic and common pathways - VII, V, X, II, fibrinogen
- Prothrombin time (PT) is the raw clotting time, while international normalised ratio (INR) is a standardised measure to account for variation of reagents between laboratories.
Practical Points
- PT/INR can be used to monitor patients on warfarin
- PT/INR does not correspond to the coagulative status of patients on novel anticoagulants such as dabigatran, rivaroxaban and apixaban
- INR does not correspond to the coagulative status of patients with liver disease, and most often these patients are also coagulopathic
- Heparin can also prolong the INR, and so heparin neutralisers are used when performing the test - excess heparin in the sample can overcome this and prolong the PT/INR
Prolonged INR
Causes of Prolong PT/INR
Isolated Prolonged PT/INR
- Warfarin (low dose)
- Mild vitamin K deficiency
- Factor VII deficiency
Prolonged PT/INR and APTT
- Artefactual - high haematocrit
- Liver disease
- Disseminated intravascular coagulation (DIC)
- Common pathway deficiency - X, V, II, fibrinogen
- Severe vitamin K deficiency
- High dose heparin
- Warfarin
- Factor IIa inhibitors (dabigatran)
- Factor Xa inhibitors (rivaroxaban, apixaban)
Approach
- Determine whether the patient is on warfarin or any other anticoagulants.
- Check the patient's haematocrit, which if elevated will falsely elevate PT/INR and APTT
- Look for evidence of chronic liver disease, either in the patient's past medical history or current clinical state.
- Assess the patient's risk of DIC given their clinical state.
- If unsure about the cause of prolonged PT/INR, mixing studies can be performed.
PT/INR Mixing Studies
The patient's plasma is mixed 50:50 with control plasma, and then the PT/INR is measured.
Significance
- PT/INR mixing studies are used to determine the cause of prolonged PT/INR.
Interpretation
- PT/INR corrects - factor deficiencyWarfarin, vitamin K deficiency, congenital factor deficiency, DIC, liver failure
- PT/INR does not correct - inhibitor presentFactor IIa inhibitors, excess heparin
INR in Warfarin Monitoring
The INR is used to monitor coagulative state of patients on warfarin, to ensure that they are receiving a therapeutic dose.
Common INR Targets
- Atrial fibrillation, DVT/PE: 2.0 - 3.0
- Mechanical heart valve: 2.5 - 3.5
Practical Points
- Consult local guidelines when commencing warfarin.
- Changes in warfarin dosing will take several days to have an effect on the INR, so dose titration should rely on the trend rather then being immediately reactive.
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