Screening for abnormalities of the protein C anticoagulant pathway using the protein C pathway test

So far, the screening for abnormalities of the protein C anticoagulant path way, which are reported in more than 30% of patients with thrombophilia, is based on the use of individual assays for protein C, protein S, and the so -called activated protein C (APC) resistance which is mainly due to the fac tor V Leiden mutation. A new generation of tests has recently been proposed to screen for all these defects and thereby to rationalize the approach to the individual assays. The Protein C Pathway Test is a clotting assay whic h is based on the ability of endogenous activated protein C, generated by a ctivation of protein C by Protac(R), to induce a prolongation of a dilute R ussell viper venom clotting time. Results were expressed as the ratio calcu lated by dividing the clotting time in the presence of the activator by tha t in its absence (saline). To evaluate its sensitivity to abnormalities of the protein C pathway, we retrospectively investigated frozen plasma sample s from 196 patients with a thrombotic history, including 17 who were under oral anticoagulant treatment. All the carriers of the factor V Leiden mutat ion (n=26) had a ratio below 1.80, and the same applied to the patients wit h protein C deficiency (n=8) or combined defects (n=3). Using such a cut-of f level, the sensitivity to both hereditary and acquired protein S deficien cy (n=44) was only 14%, Interestingly, all of the 98 patients without abnor malities of the protein C pathway had a ratio above 1.80. In addition, ail but three of the 17 patients under OAT had a ratio below 1.80, preventing a ccurate identification of those who carried the factor V Leiden mutation. T hese results suggest that the PCP Test could be used as a first step assay in the laboratory screening for APC resistance/factor V Leiden and protein C in patients not treated by oral anticoagulants, The corresponding specifi c assays would be performed only in case of a ratio below a well defined cu t-off (1.80 in this study), but the measurement of protein S had to be perf ormed in all cases.