ProC Global: a new assay to evaluate the functionality of the protein C anticoagulant pathway - Preliminary results in 223 consecutive patients with a history of venous thromboembolism

ProC Global is a new clotting assay designed to globally evaluate the funct ionality of the protein C anticoagulant pathway, which is defective in more than 30% of Caucasian patients with thrombophilia. Briefly, the assay is b ased on the ability of endogenous activated protein C, generated by activat ion of protein C by Protac, to prolong an activated partial thromboplastin time. Clotting times are measured in the presence and absence of Protac, an d the results are expressed, in PCAT-NR, after normalization with a lyophil ized standard plasma. To determine the ability of this assay to distinguish patients with and without abnormalities of the protein C anticoagulant pat hway, we tested frozen plasma samples from 223 consecutive patients with a history of thrombosis referred to the laboratory for screening of biologica l risk factors for thrombosis, 41 of whom were on oral anticoagulant therap y (OAT). All heterozygous carriers of the factor V Leiden mutation (n = 15) , as well as patients with protein C deficiency (n = 6) or combined defects (n = 3), had a PCAT NR below 0.75. Sensitivity for hereditary or acquired protein S deficiency (n = 16) was only 63%. The specificity of the assay wa s 70%, as about 30% of the patients with no known abnormality of the protei n C pathway had a PCAT NR below this cut-off. However, the assay performed poorly in samples from patients on OAT, as the PCAT NR was reduced in 93% o f such cases. These results suggest that the ProC Global assay could be use d as a first-step screening test for protein C deficiency and factor V Leid en-related APC resistance, and that individual assays be performed only whe n the PCAT-NR is below a well-defined cut-off. However, given the only mode rate sensitivity of the assay for protein S deficiency, this coagulation in hibitor must be determined in every case.