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.