Reliability and clinical impact of the normalization of the prothrombin times in oral anticoagulant control.

In 1983, the World Health Organization (WHO) published recommendations for normalization, in oral anticoagulant control, of the prothrombin time (PT). The common denominator is the International Sensitivity Index (ISI) of a thromboplastin, obtained by means of thromboplastin calibration. The common scale is that of the International Normalized Ratio (INR). The INR is the PT ratio (Formula: see text) which would have been found with the WHO primary international reference preparation (IRP) 67/40. The reliability of the INR depends on the extent of calibration precision, patient-specific influences, as well as inter-laboratory variation in the PT determination. Under well-controlled conditions the overall coefficient of variation (CV) of the INR is 11-13.5%, if thromboplastins of ISI congruent to 1 are used. For so-called low-sensitivity thromboplastins (ISI congruent to 2-2.5), the overall variation is larger due to a large between-laboratory variation of the measured PT-ratios. The user of thromboplastin will be provided with a chart or graph enabling him to convert the conventional terms used for expressing PTs into INRs. For quality assurance, and to prepare his own calibration chart if necessary, he should check normalization by means of control plasmas to which INRs have been assigned. There is sufficient clinical evidence to express optimal therapeutic ranges in terms of INR. Manufacturers should revise and adapt their inserts where necessary in order to conform to these requirements.