SummaryInterpretation of protein C (PC) levels in a given individual has several limitations. A normal PC activity does not necessarily exclude a genetic deficiency nor can a reduced level confirm it. Measuring PC amidolytic activity in 9,648 healthy blood donors has allowed identification of demographic factors which cause variation in PC activity and further hinder interpretation. PC activity displays a log normal distribution and significant variation with age. This is most marked in young adult males when mean PC activity rises from 0.86 iu/ml (15–19 years) to 1.04 iu/ml (45–49 years; P <0.0001). Pre-menopausal females, who for most age ranges, have mean PC activity below their male contemporaries, show a less marked rise with age until the menopause when PC activity rises further. The use of hormonal contraceptive preparations is associated with an increase in mean PC activity of 0.05–0.08 iu/ml while smoking habit has no influence on PC activity.In view of these findings we strongly recommend the use of age and sex restricted reference ranges when interpreting PC activity.
Antithrombin III (AT III) activity has been measured in 9669 healthy blood donors (5525 male and 4144 female). The distribution of AT III is approximately 'normal' with mean 105.6 IU/dl and standard deviation 11.2; however, definite age and sex related variations are evident. Pre-menopausal females have lower mean AT III compared to their male contemporaries who have remarkably stable mean AT III until 45 years, after which there is a gradual decline. In contrast, post-menopausal females have higher mean AT III than both males of the same age and younger pre-menopausal females. Concurrent hormone replacement therapy inhibits this rise. The use of hormonal preparations is associated with a 4 IU/dl reduction of mean AT III in younger females but not in those over 30 years. Smoking may result in a mild increase in AT III of doubtful clinical significance. On-going genetic and family studies are expected to predict a prevalence rate of congenital AT III deficiency in excess of the previously reported figure of 0.02%. The authors consider these observed variations as minor and recommend the use of a single reference range for AT III activity, but that particular care be taken when interpreting results in pill-taking females and the elderly.
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