No effect of the prothrombin G20210A mutation on protein C activation in a large kindred with type I protein C deficiency.
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.
Vossen
Carla Y
CY
Department of Pathology, University of Vermont, Burlington, Vermont 05405, USA.
Strandberg
Karin
K
Stenflo
Johan
J
Rosendaal
Frits R
FR
Callas
Peter W
PW
Long
George L
GL
Bovill
Edwin G
EG
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*
D011486:Protein C; D018046:Protein C Inhibitor; D011516:Prothrombin