What is the major effect of using the International Normalized Ratio (INR) in evaluating patients on oral anticoagulation, such as warfarin (coumarin)?

The Major Effect of Using the International Normalized Ratio (INR) in Evaluating Patients on Oral Anticoagulation

The major effect of using the International Normalized Ratio (INR) in evaluating patients on oral anticoagulation is that it allows the thromboplastins produced by different manufacturers to be standardized, resulting in standardization of PT monitoring of oral anticoagulation. 1

Why INR Standardization Was Necessary

Prior to the adoption of the INR system, PT monitoring of warfarin treatment was very imprecise when expressed as a simple PT ratio (calculated as the patient's plasma value over normal control plasma) due to significant variability in thromboplastin reagents:

• Thromboplastins varied markedly in their responsiveness to warfarin according to their source, phospholipid content, and preparation 1
• Different thromboplastins produced different PT results for the same degree of anticoagulation 1
• This variability contributed to clinically important differences in oral anticoagulant dosing between countries 1
• In North America, the use of less responsive thromboplastins led to excessive and erratic anticoagulation 1

How the INR System Works

The INR standardization system works through:

1. Converting the PT ratio measured with local thromboplastin into an INR using the formula:

   • INR = (patient PT/mean normal PT)^ISI 1

2. Using the International Sensitivity Index (ISI) to account for thromboplastin sensitivity:

   • The ISI reflects the responsiveness of a given thromboplastin to reduction of vitamin K-dependent coagulation factors 1
   • More responsive reagents have lower ISI values 1
   • In 1992, ISI values of thromboplastins used in the United States varied between 1.4 and 2.8 1

Clinical Impact of INR Standardization

The adoption of the INR standard has had significant clinical benefits:

• Improved safety of oral anticoagulant therapy 1
• Enhanced ease of monitoring 1
• Allowed reliable comparison between medical institutions and clinical trials worldwide 1
• Facilitated the development of consistent therapeutic ranges for different clinical conditions 2

Common Pitfalls and Caveats

Despite its benefits, there are important limitations to the INR system:

• The INR is less reliable early in the course of warfarin therapy, particularly when results are obtained from different laboratories 1
• The INR was specifically designed for monitoring vitamin K antagonist therapy and has limited validity in other clinical contexts 2
• Low-sensitivity thromboplastins may give erroneously high INRs in the upper therapeutic range 3
• Plasma prothrombin times should be done with a high-sensitivity thromboplastin, particularly in patients maintained at the upper limit of the therapeutic range 3

Clinical Application

The INR system enables consistent therapeutic targets across different clinical scenarios:

• Venous thromboembolism: Target INR 2.0-3.0 2, 4
• Atrial fibrillation: Target INR 2.0-3.0 2, 4
• Mechanical heart valves: Target INR 2.5-3.5 for mitral position or aortic with risk factors 2, 4
• Post-myocardial infarction: Target INR varies based on risk factors and concurrent aspirin use 4

The implementation of the INR standard in the United States increased from 21% to 97% between 1991 and 1997 1, demonstrating its widespread acceptance and critical importance in standardizing anticoagulation monitoring.