Why Check INR in Patients Not on Warfarin
The INR was specifically designed and validated only for monitoring vitamin K antagonist (warfarin) therapy and should not be used as a general coagulopathy screen in patients not taking warfarin. 1
The Fundamental Problem with INR Testing in Non-Warfarin Patients
The INR standardization process was developed by comparing clotting times measured on plasma samples obtained exclusively from patients on stable warfarin therapy, and specifically excluded patients with underlying bleeding tendencies, acute medical illness, liver disease coagulopathy, or those receiving other anticoagulant agents. 1 This means the test is fundamentally invalid outside this narrow context.
There is no high-quality evidence that INR values predict bleeding risk in patients not receiving vitamin K antagonist therapy. 1
When INR Testing Might Still Be Ordered (Despite Limited Validity)
Despite its lack of validation, clinicians may order INR in non-warfarin patients for several reasons, though each has significant limitations:
1. Suspected Liver Disease Assessment
- The INR is incorporated into the MELD score for liver transplant candidates, but paradoxically does not predict their bleeding risk either spontaneously or in connection with procedures. 1
- If liver synthetic function were truly impaired enough to cause INR elevation, other abnormalities would typically be present: decreased albumin, elevated bilirubin, elevated GGT (present in >85% of chronic liver disease), and thrombocytopenia from hypersplenism. 2
- The INR in liver disease reflects both decreased procoagulant factors and decreased anticoagulant factors, creating a rebalanced hemostatic state that is fundamentally different from warfarin-induced coagulopathy. 2
2. Pre-Procedural Bleeding Risk Assessment
- A systematic review of 79 studies found weak (sensitivity under 50%) or no association between INR and bleeding in pre-procedural patients. 1
- Randomized clinical trials in periprocedural, critically ill, and liver disease patients found no reduction in bleeding when prophylactic plasma was given to correct INR values. 1
- The INR does not predict bleeding risk in patients with or without cirrhosis undergoing procedures. 1
3. Investigation of Unexplained Bleeding or Coagulopathy
- When investigating an elevated INR in a non-warfarin patient, immediately assess for bleeding and determine underlying pathology rather than treating the number itself. 3
- Check comprehensive liver function tests (albumin, bilirubin, transaminases), complete blood count with platelets, and consider vitamin K deficiency. 3
- The INR is a poor predictor of factor levels in patients with disseminated intravascular coagulation, massive transfusion, and acute trauma. 1
Critical Pitfalls to Avoid
Never transfuse plasma to "correct" mildly elevated INR in non-bleeding patients not on warfarin. 1, 3 This practice:
- Lacks biological plausibility because plasma infusion does not change INR values below 1.5 and only minimally impacts values below 2.0 1
- Has no evidence for reduced bleeding at these targets 1
- Exposes patients to volumetric and immunologic risks requiring large doses (20 mL/kg or 1.4 liters in a 70 kg patient) 1
- Increases portal pressure in liver disease patients without improving hemostasis 2
Never use INR as a screening test for inherited thrombophilias like Factor V Leiden. 4 The INR is normal in these conditions as they do not affect the extrinsic or common coagulation pathways measured by PT/INR testing. 4
The Bottom Line
If an INR is ordered in a non-warfarin patient and comes back elevated, this should prompt investigation for underlying liver disease, vitamin K deficiency, or other specific coagulopathies—not treatment of the INR number itself. 3 The test result lacks the predictive validity for bleeding risk that it has in warfarin-treated patients, and treating the number rather than the underlying condition represents a fundamental misunderstanding of what the INR measures. 1