Reference materials and reference measurement systems in laboratory medicine. Prothrombin time standardization: the...

The prothrombin time of fresh normal pooled plasma and the mean normal prothrombin time are currently recommended as the denominator term in the expression of prothrombin time ratios and International Normalised Ratio (INR) values. Fresh normal pooled plasma is also required for correct extrapolation of percent prothrombin time activity values. To avoid collection and measurement of a relevant number of normal individual samples for calculation of the mean normal prothrombin time or the necessity for a fresh plasma pool, lyophilised normal control plasma is made available by the manufacturers of thromboplastin reagents. The Verband der Diagnostica- und Diagnostikgerätehersteller (VDGH) has adopted a lyophilised normal pooled plasma (R82A) which was calibrated in two studies against fresh normal plasma pools and fresh individual normal plasmas, using a variety of plain and combined thromboplastins. Both studies concluded that plasma R82A could be used as a substitute for normal plasma, but a correction should be made for plain thromboplastin reagents. These data have been confirmed in an IFCC collaborative international study organised by the IFCC Working Group Standardisation of Coagulation Tests. In the latter study, in addition to plain and combined thromboplastin reagents, the recently introduced recombinant thromboplastins were evaluated and they showed a significant deviation from the sensitivity observed with extracted thromboplastins. Recombinant thromboplastins are under consideration as future international reference thromboplastins; the results of the IFCC collaborative study call for additional experimentation before this is accomplished.