THE INTERNATIONAL NORMALIZED RATIO AND UNCERTAINTY - VALIDATION OF A PROBABILISTIC MODEL

The motivation behind the creation of the International Normalized Rat io (INR) was to improve interlaboratory comparison for patients on ant icoagulation therapy. In principle, a laboratory that reports the prot hrombin time (PT) as an INR can standardize its PT measurements to an international reference thromboplastin. Using probability theory, the authors derived the equation for the probability distribution of the I NR based on the PT, the International Sensitivity Index (ISI), and the geometric mean PT of the reference population. With Monte Carte and n umeric integration techniques, the model is validated on data from thr ee different laboratories. The model allows computation of confidence intervals for the INR as a function of PT, ISI, and reference mean. Th e probabilistic model illustrates that confidence in INR measurements degrades for higher INR values. This occurs primarily as a result of a mplification of between-run measurement errors in the PT, which is inh erent in the mathematical transformation from the PT to the INR. The p robabilistic model can be used by any laboratory to study the reliabil ity of its own INR for any measured PT. This framework provides better insight into the problems of monitoring oral anticoagulation.