Clinical utilization of the international normalized ratio (INR)

The prothrombin lime (PT) is one of the most important laboratory tests to determine the functionality of the blood coagulation system. It is used in patient care to diagnose diseases of coagulation, assess the risk of bleedi ng in patients undergoing operative procedures, monitor patients being trea ted with oral anticoagulant (coumadin) therapy, and evaluate liver function . The PT is performed by measuring the clotting time of platelet-poor plasm a after the addition of calcium and thromboplastin, a combination of tissue factor and phospholipid. Intra- and interlaboratory variation in the PT wa s a significant problem for clinical laboratories in the past, when crude e xtracts of rabbit brain or human placenta were the only source of thrombopl astin. The international normalized ratio (INR), developed by the World Hea lth Organization in the early 1980s, is designed to eliminate problems in o ral anticoagulant therapy caused by variability in the sensitivity of diffe rent commercial sources and different lots of thromboplastin to blood coagu lation factor VII. The INR is used worldwide by most laboratories performin g oral anticoagulation monitoring, and is routinely incorporated into dosag e planning for patients receiving warfarin. Although the recent availabilit y of sensitive PT reagents prepared from recombinant hu man tissue facto r (rHTF) and synthetic phospholipids eliminated many of the earlier problems associated with the use of crude thromboplastin preparations, local instrum ent variability in the INR still remains a problem. Presently, the use of p lasma calibrants seems the best solution to this problem. Standardizing the point-of-care instruments for INR monitoring is another dilemma faced by t he industry. Ultimately, new generations of anticoagulant drugs may elimina te the need for laboratory monitoring of anticoagulant therapy. (C) 2000 Wi ley-Liss, Inc.