Influence of demographic factors on antithrombin III activity in a healthy population

Abstract

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.

Determinants of Elevated Levels of Natural Anticoagulants in Healthy Subjects

“…The plasma levels of natural anticoagulants exceeding the upper limit of reference ranges have been associated with age and gender [9][10][11][12]. Boerger et al was the first who reported that free PS levels are higher in men than in women at all ages which has been confirmed by other studies [9,13].…”

Normal ranges and genetic variants of antithrombin, protein C and protein S in the general Chinese population. Results of the Chinese Hemostasis Investigation on Natural Anticoagulants Study I Group

“…The following key words were used: antithrombin, protein C protein S, Asia population, genetic populations, database, reference ranges. This search did yield some reports of normal ranges for small Asian or Caucasian groups but only a few reports concerned large series of healthy cohorts for Western [21][22][23][24][25][26][27][28][29] or Eastern 20,31,32 countries (Online Supplementary Table S3). The largest studies from Asia were conducted in Japan.…”

“…Some publications have reported age-and gender-related normal ranges of AT, PC and PS activities in large series of healthy Western individuals. [21][22][23][24][25][26][27][28][29] However, such reference ranges have only been reported in small series of Asians, except in Japanese. 20,[30][31][32] As variations can be expected between populations of different ethnic backgrounds, the results published for Caucasians should not be extrapolated to the Chinese and, likewise, results from Japanese series may differ from those for Chinese people.…”

Inherited and Acquired Thrombophilia in Pregnancy

“…The clinical relevance of a distinction between antithrombin I and antithrombin II deficiency lies in the higher risk of thrombosis associated with the type I variety. The prevalence of type I mutations in the general population is of the order of 0.02% (Tait et al, 1993). The relative risk of venous thromboembolism is around 25 to 50 -fold for individuals with type I antithrombin deficiency .…”

“…Activated protein C is only effective when bound to its cofactor protein S. Protein S is available as a cofactor for protein C only when it is bound to Cbinding protein. In the basal state, approximately forty percent of protein S is free (unbound) and thereby is available to serve as a cofactor for activated protein C. In the clotting pathway, the activated protein C/protein S complex degrades factors Va and factor VIIIa, and their loss is associated with a decrease in fibrin formation and hence a reduced ability to form a fibrin clot (Tait et al, 1993). The activated form of factor V enhances the activation of prothrombin by several thousand-fold (Nesheim et al, 1979;Rosing et al, 1980).…”