Challenges in PT/INR harmonization across the total testing process

The International Normalized Ratio (INR), introduced by the World Health Organization in 1983, is central to vitamin K antagonist (VKA) therapy monitoring. However, thromboplastin standardization alone does not ensure harmonized prothrombin time (PT)/INR results. Residual variability arises throughout the testing continuum. In this narrative review, we examine the principal sources of residual PT/INR non-equivalence across the "vein-to-report" pathway. Particular attention is devoted to clinical settings in which the assumptions underlying INR calibration are only partially satisfied, including advanced liver disease and exposure to direct oral anticoagulants. We further discuss postanalytical factors, such as determination of the mean normal prothrombin time and system-specific verification of the International Sensitivity Index, as well as quality assurance strategies, including the use of commutable external quality assessment materials and patient-based real-time quality control. Prothrombin time/INR harmonization requires integrating preanalytical practices, recognizing reagent-instrument dependencies, and quality strategies reflecting real-world testing conditions.