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Coagulation
 
 

International Normalised Ratio (INR)

 
 
 
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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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