title: No effect of the prothrombin G20210A mutation on protein C activation in a large kindred with type I protein C deficiency.
abstract: Previously, we observed a positive association of prothrombin concentrations with thrombin generation (fragment 1 + 2) and thrombin activity (fibrinopeptide A), but no association with protein C activation peptide levels. We further evaluated a potential beneficial effect of increased prothrombin concentrations on activated protein C generation by assessing the plasma concentration of activated protein C in complex with protein C inhibitor (APC-PCI). Blood samples were used from 195 family members of a large French-Canadian kindred with type I protein C deficiency due to a 3363C insertion in the protein C gene. We utilized a new and highly sensitive assay for measuring the concentration of APC-PCI complex as a measure of the level of activation of protein C. Means of the plasma concentrations of the APC-PCI complex were compared among carriers and non-carriers of the prothrombin G20210A mutation. Protein C activity levels were positively associated with APC-PCI complex plasma concentrations; however, APC-PCI complex levels were not different for carriers of the prothrombin G20210A mutation than for non-carriers. Thus, carriers of the prothrombin G20210A mutation do not have increased protein C activation despite the increased thrombin generation resulting from the higher prothrombin concentrations associated with the G20210A mutation.
authors.affiliation: Department of Pathology, University of Vermont, Burlington, Vermont 05405, USA.
authors.forename: Carla Y
authors.initials: CY
authors.lastname: Vossen
authors.forename: Karin
authors.initials: K
authors.lastname: Strandberg
authors.forename: Johan
authors.initials: J
authors.lastname: Stenflo
authors.forename: Frits R
authors.initials: FR
authors.lastname: Rosendaal
authors.forename: Peter W
authors.initials: PW
authors.lastname: Callas
authors.forename: George L
authors.initials: GL
authors.lastname: Long
authors.forename: Edwin G
authors.initials: EG
authors.lastname: Bovill
mesh_terms: D001780:Blood Coagulation Tests; D005260:Female; D006801:Humans; D008297:Male; D009154:Mutation; D011486:Protein C / Q000032:analysis* / Q000235:genetics; D020151:Protein C Deficiency / Q000097:blood* / Q000235:genetics; D018046:Protein C Inhibitor / Q000097:blood*; D011516:Prothrombin / Q000032:analysis* / Q000235:genetics*
chemical_list: D011486:Protein C; D018046:Protein C Inhibitor; D011516:Prothrombin