Protein CVermont: Symptomatic Type I1 Protein C Deficiency Associated With Two GLA Domain Mutations

This study investigates type II protein C deficiency in a family with manifestations of both arterial and venous thrombosis. Of 64 members of the kindred, 14 have been tested and 7 have PC deficiency. Among affected individuals (n = 7). mean protein C levels by different assays were as follows: enzyme-linked immunosorbent assay (ELISA), 3.8 pg/mL (2.1 to 4.3 pg/mL); amidolytic with venom activator, 115 % (60 % to 140%); clotting with venom activator, 42 % (23 % to 59%). The mean ratio of clotting to amidolytic assays for the affected individuals was 0.37 compared with a normal range of 0.8 to 1.2. Thus, the affected individuals have normal total protein C and their activated protein C has a normal active site assessed by chromogenic substrate; however, they have markedly diminished clotting activity. Immunoassay and chromatography data suggested an abnormality of carboxy