FRENCH MULTICENTRIC EVALUATION OF RECOMBINANT TISSUE FACTOR (RECOMBIPLASTIN) FOR DETERMINATION OF PROTHROMBIN TIME

Recombiplastin, a recombinant a human tissue factor, elaborated by Ort ho Diagnostic Systems, produced by Baculovirus and relipidated with hi ghly purified phospholipids, was tested as a new reagent for determini ng prothrombin time (PT) in a French multicentric study. Its intralabo ratory performances, including sensitivity, repeatability, reproducibi lity and stability, were explored to establish whether its use would r educe the interlaboratory dispersion of PT values, and therefore impro ve the standardization of oral anticoagulant treatment. The 9 universi ty hospital hematology laboratories involved in this study used the sa me type of instrument (KC 10). For 10 consecutive days, they determine d PTs on a normal plasma pool, plasma dilutions of 1/2, 1/3 and 1/8, 3 identical lyophilized calibrated plasmas, as well as plasmas from 20 normal subjects, 50 patients on oral anticoagulant therapy with Recomb iplastin which has an International Sensitivity Index (ISI) of 1, acid 2 commercial thromboplastin extracts (ISI #1 or 2). In the patients o n anticoagulants, factors VII, X and V were measured when results were conflicting. The intra and interlaboratory reproducibilities of Recom biplastin, calculated on the basis of either PT, expressed in seconds, or of the International Normalized Ratio (INR), were good, with coeff icients of variation (CV) similar to those observed with the 5 other r eagents used by the different laboratories (2% <CV <8%). The stability of Recombiplastin was excellent, with no variation in PT after 72 h o f incubation at 37 degrees C. A normal PT of 12 s was obtained with Re combiplastin, similar to the values found for the, reagents with ISI # 2. In the patients on anticoagulants, Recombiplastin gave the longest coagulation times (PTRecombipiastin = 64.2 s vs PTNeoplastin = 32.8 s, and PTThromborel = 54.4 s). These results suggest that Recombipiastin is highly sensitive to the changes in coagulation induced by anticoag ulants. Recombiplastin was more sensitive to factor VII deficiency tha n any of the other reagents, even those with ISI #1. The coefficients of correlation between the INR, calculated on the basis of the PTs obt ained with Recombiplastin and the INR, based on the PTs for other thro mboplastins, were satisfactory (0.85 <R <0.95) but a breakpoint in the slope of the regression curves was observed when WR >4. This observat ion requires further investigation, particularly in connection with th e exact ISI values for Recombiplastin and the other thromboplastins us ed in this study. In conclusion, Recombiplastin is stable and sensitiv e and gives accurate reproducible results. However, the behavior of Re combiplastin is slightly different from that of the commercial reagent s whether their ISI is 1 or 2, and its use did not reduce the interlab oratory dispersion of PT values.