Absence of thrombosis in subjects with heterozygous protein C deficiency.
Protein C deficiency has been thought to be associated with an increased risk of venous thrombosis. To establish a normal range of values, we used a two-site monoclonal-antibody assay to measure protein C levels in 699 healthy adults. The distribution was log normal; 95 percent of the values ranged from 70 to 140 percent of the overall mean (4.03 micrograms per milliliter). Two subjects had levels more than 3.5 SD below the mean (34 and 50 percent), consistent with heterozygous deficiency. We also screened 4723 other blood donors and found 8 additional unrelated subjects with levels from 33 to 51 percent of normal. Autosomal inheritance of heterozygous protein C deficiency was confirmed in them by a detailed study of four families. Levels from 55 to 65 percent of normal are consistent with either heterozygous deficiency or the lower end of the distribution of normal values, and were found in 79 of 5422 subjects when the two groups were combined. None of the subjects had any history of venous thrombosis. We conclude that heterozygous deficiency of protein C has a prevalence of 1 in 200 to 300, a figure consistent with the known number of homozygous infants recently identified, and that levels consistent with heterozygous deficiency are found in 1 in 60 healthy adults but are not detectably associated with a risk of thrombosis.
Miletich
J
J
Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110.
Sherman
L
L
Broze
G
G
D000328:Adult; D000911:Antibodies, Monoclonal; D006579:Heterozygote; D006801:Humans; D008875:Middle Aged; D011486:Protein C / Q000032:analysis / Q000276:immunology; D020151:Protein C Deficiency; D012307:Risk Factors; D013924:Thrombophlebitis / Q000150:complications* / Q000235:genetics
D000911:Antibodies, Monoclonal; D011486:Protein C