TInternational Normalized Ratio (INR) is the accuracy of the Prothrombin Time (PT) is known to be very system-dependent. The World Health Organization has addressed this system variability problem by (1) the establishment of primary and secondary international reference preparations of thromboplastin and (2) the development of a statistical model for the calibration of thromboplastins to derive the International Sensitivity Index (ISI) and the INR.

The INR uses the ISI to equate all thromboplastins to the reference thromboplastin through the following equation:

INR = (patient PT/mean normal PT)ISI

Thus, the INR can be calculated using the working prothrombin time ratio once the ISI of the thromboplastin is known.

Documented differences in PT results in several interlaboratory trials led the International Committee on Thrombosis and Hemostasis to make a joint recommendation in 1983 to express all PTs as INRs and that manufacturers indicate the ISI of their thromboplastin reagents.

Recommendations for extent of anticoagulation based on INR can be found in "Antithrombotic and Thrombolytic Therapy, 8th Ed: ACCP Guidelines", published in the June, 2008 (Supplement) issue of Chest. This contains recommendations of many specialists for the prevention of thromboembolism. It addresses anticoagulation in various diseases, conditions and other related topics. In brief they "A recommendation of an INR of 2.0 to 3.0 is made for most indications. For further monitoring recommendations refer to the Guidelines publication.

Patients are widely variable in response to oral anticoagulation. In addition, early efforts to use the INR among laboratories has had some problems. The guidelines can be helpful in monitoring patients but they should not replace sound clinical judgment.

Studies have shown that low ISI (high sensitivity) reagents are optimal. The laboratory will choose reagents with ISI.[1]