A unique family with
protein C (PC) deficiency is described. The proband had a history of renal vein
thrombosis as a newborn and iliofemoral
thrombosis at the age of 6 years. After 6 months of
heparin treatment, discontinuation of anticoagulation
therapy was accompanied by persistent hypofibrinogenemia with increased
fibrinogen consumption. With continuous infusion of
heparin,
fibrinogen turnover normalized, and the child has remained free of
thrombosis. Both the immunologic level of PC and the functional activity measured by amidolytic assay were moderately reduced (47% and 34%, respectively). Functional activity of PC measured by its
anticoagulant activity was disproportionately lower (14%). A 3-year-old asymptomatic sibling had a similar disproportionate reduction of PC
anticoagulant activity compared with the amidolytic activity or immunologic level. The mother demonstrated type I PC deficiency with a proportionate reduction in immunologic
protein levels (59%),
anticoagulant activity (52%), and amidolytic activity (46%), whereas the father had type II PC deficiency with normal immunologic
protein levels (102%), normal amidolytic function (98%), but a low
anticoagulant function (50%). An abnormal PC molecule was detected by two-dimensional immunoelectrophoresis in the father and two children. These data are consistent with the hypothesis that the children are doubly heterozygous for two different types of PC deficiency inherited from each of the parents. A 14-day trial of
danazol in the proband resulted in a rise in the PC
antigen concentration from 66% to 98% but no change in PC
anticoagulant function.