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Summary ProC Global is a new clotting assay designed to globally evaluate the functionality of the protein C anticoagulant pathway, which is defective in more than 30% of Caucasian patients with thrombophilia. Briefly, the assay is based on the ability of endogenous activated protein C, generated by activation of protein C by Protac, to prolong an activated partial thromboplastin time. Clotting times are measured in the presence and absence of Protac, and the results are expressed, in PCAT-NR, after normalization with a lyophilized standard plasma. To determine the ability of this assay to distinguish patients with and without abnormalities of the protein C anticoagulant pathway, we tested frozen plasma samples from 223 consecutive patients with a history of thrombosis referred to the laboratory for screening of biological risk factors for thrombosis, 41 of whom were on oral anticoagulant therapy (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 was 70%, as about 30% of the patients with no known abnormality of the protein 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% of such cases. These results suggest that the ProC Global assay could be used as a first-step screening test for protein C deficiency and factor V Leiden-related APC resistance, and that individual assays be performed only when the PCAT-NR is below a well-defined cut-off. However, given the only moderate sensitivity of the assay for protein S deficiency, this coagulation inhibitor must be determined in every case. |
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