Protein C deficiency resulting from possible double heterozygosity and its
response to danazol
RA Gruppo, P Leimer, RB Francis, RA Marlar and E Silberstein
Children's Hospital Medical Center, Cincinnati, OH 45229.
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.
Volume 71,
Issue 2,
pp. 370-374,
02/01/1988
Copyright © 1988 by The American Society of Hematology
