From vitamin K antagonists to liver international normalized ratio: a historical journey and critical perspective

Adoption of international normalized ratio (INR) to harmonize prothrombin time has greatly improved the safety and effectiveness of vitamin K antagonists (VKA) oral anticoagulant therapy. INR is also a major laboratory variable in calculating the widely used Model for End-Stage Liver Disease (MELD) score for liver transplant organ prioritization. However, since the conventional INR (INRVKA) is calibrated specifically for VKA patients, its interlaboratory variation has a significant impact on the accuracy of MELD score. Though still requiring further clinical validation in large numbers of waitlisted patients, the alternative liver INR calibrated by using plasma from liver disease patients instead of VKA patients may harmonize the differences and thus more suitable for MELD score calculation. The objective of this article is to review the history of INR, MELD score, and liver INR, and discuss the challenges and solutions of liver INR implementation.