The latest research & treatment news about Hepatitis C infection, diagnosis, symptoms and treatment.

Standard Reporting The International Normalized Ratio (INR)

Standard Reporting The International Normalized Ratio (INR), adopted by the World Health Organization (WHO) in 1983, attempts to address the many variables associated with the measure of warfarin effectiveness. The INR is a standardized system of reporting PT, based on a referenced calibration model and calculated by comparing the patient’s PT with a control value. Factored into this calculation is the International Sensitivity Index (ISI), also developed by WHO, which is a determination of each reagent’s degree of sensitivity, compared with that of a specific reference thromboplastin (which was assigned an ISI of 1.0).4 The ISI allows the associated PT ratio to be normalized to an International Reference Preparation.6

Acceptance of the INR in the United States has been slow.3This is surprising, considering the INR’s potential value as a marker–one that allows for comparisons of values, regardless of the source or sensitivity of the thromboplastin reagent used. This allows for consistency in evaluation and treatment.

Currently, the desired INR for most moderate-intensity warfarin regimens is between 2.0 and 3.0.5 However, more intensive therapy may require higher INR values5–although an INR higher than 4 is considered dangerous because of the increased risk of bleeding.

Patients for whom oral anticoagulation therapy is planned should have baseline studies, including a PT. Because individual patient response to anticoagulant therapy varies, INR values are most useful after 1 to 2 weeks, when adequate time has been allowed for individual response. The INR then provides a very consistent and reliable tool for the clinician and patient, eliminating the variability that can occur in the PT:control ratio system due to differences in reagent sensitivity. Results from any lab that uses the INR process can be considered consistent. Typically, the laboratory report will indicate the patient’s PT and the INR. If the INR is in the desired range, a PT value that is high or low (most likely due to varying reagent sensitivity) should not present a problem. The INR represents a standardized value and the one for guiding treatment.

As therapeutic outcomes come to be measured more consistently in relation to INR values, clinical data will become better established and more specific therapeutic values will be identified.

Short of requiring all laboratories to use a standard thromboplastin, 4 it is important that patients be monitored at the same laboratory using the same or similar reagents during the initial treatment phase,7 a period of time which may last as long as 2 weeks. The American College of Chest Physicians has recommended using thromboplastin reagents with an ISI of 1.2 or less to increase reliability in INR reporting.7 This becomes less important once the initial treatment period has passed. Conclusion Introduced 14 years ago to the United States and gaining acceptance slowly, the INR nearly eliminates variability in PT by taking into account the possible variations in reagent sensitivity. The INR provides a consistent monitor for oral anticoagulation therapy that makes it a very useful tool for clinicians.


J. Dennis Blessing, Jean Bybee-Pierson, Shirley Richmond

1.Physicians’ Desk Reference. 50th ed. Montvale, NJ: Medical Economics; 1996:926-929.

2.Fischbach FT. A Manual of Laboratory & Diagnostic Tests. 5th ed. Philadelphia, Pa: JB Lippincott; 1996:124-131.

3.Hirsh J. Oral anticoagulant drugs. N Engl J Med. 1991;324:1865-1875.

4.Eckman MH, Levine HJ, Pauker SG. Effect of laboratory variation in the prothrombin-time ratio on the results of oral anticoagulant therapy. N Engl J Med. 1993;329:696-702.

5.Brigden ML. When bleeding complicates oral anticoagulant therapy. Postgrad Med. 1995;98:153-168.

6.Lotspeich-Steininger CA, Stiene-Martin EA, Koepke JA. Clinical Hematology. Philadelphia, Pa: JB Lippincott; 1992:704.

7.Brigden ML. Oral anticoagulant therapy. Postgrad Med. 1996; 99:81-102.