Screening for abnormalities of the protein C anticoagulant pathway using the ProC Global assay. Results of a European multicenter evaluation

ProC Global is a new global clotting assay designed to evaluate the functio nality of the protein C anticoagulant pathway. It is based on the ability o f endogenous activated protein C, generated by activation of protein C by P rotac(R), to prolong an activated partial thromboplastin time, and the resu lts are expressed in protein C activation time normalized ratio (PCAT-NR), after normalization. This multicenter trial involving five European laborat ories was designed in order to determine the ability of the ProC Global ass ay to distinguish patients with and without abnormalities of the protein C pathway. The PCAT-NR was significantly lower in the patients with a thrombo tic history not on oral anticoagulant treatment (n = 627) than in the healt hy controls (n = 148), even after exclusion from both groups of the patient s with abnormality of the protein C pathway. Using receiver operator charac teristics analysis, the cut-off level of PCAT-NR = 0.80 was found to provid e the best sensitivity-specificity ratio, All the carriers of the factor V Leiden mutation (n = 73), as well as all the patients with activated protei n C resistance (n = 42), had a PCAT-NR below 0.80. The ProC Global assay pe rformed well in patients with combined defects (97.0%, n = 33) or protein C deficiency (91.3%, n = 46), but it failed to detect all of them, and one p atient with combined defects as well as four patients with a low protein C level had a PCAT-NR above the cut-off level. The sensitivity of the assay f or protein S deficiency (n = 58) was weak (only 69.0%) and, surprisingly, m ore than 40% of the 375 patients without any of these abnormalities of the protein C pathway had a PCAT-NR below the cut-off level. (C) 2000 Lippincot t Williams & Wilkins.