Plasma Levels of Protein S, Protein C, and Factor X: Effects of Sex, Hormonal State and Age

Abstract

SummaryWe measured total and free protein S (PS), protein C (PC) and factor X (FX) in 393 healthy blood donors to assess differences in relation to sex, hormonal state and age. All measured proteins were lower in women as compared to men, as were levels in premenopausal women as compared to postmenopausal women. Multiple regression analysis showed that both age and subgroup (men, pre- and postmenopausal women) were of significance for the levels of total and free PS and PC, the subgroup effect being caused by the differences between the premenopausal women and the other groups. This indicates a role of sex-hormones, most likely estrogens, in the regulation of levels of pro- and anticoagulant factors under physiologic conditions. These differences should be taken into account in daily clinical practice and may necessitate different normal ranges for men, pre- and postmenopausal women.

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

“…Age-and sex-related tendencies were found to be similar in the Chinese population and three other populations from Scotland, 28 Italy 27 and Japan. 20 These four studies and a number of other reports 26,[45][46] were concordant in showing that PS levels were lower in women than in men, with the values being lowest before the age of 45 years, 50 as in our study. Interestingly, the findings of the Japanese studies were most closely similar to those in our study.…”

“…The differences in protein activities between men and women, especially for PS, might indicate a role of sex hormones, most likely estrogens, in the regulation of anticoagulant factors levels under physiological conditions, as already reported, 45,46 although other mechanisms have been proposed. Falkon et al 47 found no relationship between estradiol levels and total or free PS concentration and suggested that low PS levels in young women might result from a combined effect of diverse stimuli on PS synthesis and/or metabolism.…”

Protein S levels and the risk of venous thrombosis: results from the MEGA case-control study

“…25 we also estimated the effect of obesity on protein S levels. Mean differences were adjusted for age and gender, as both age and gender influence protein S levels, 26 and for each other in a multivariate analysis. Because there is no reason to assume that low levels of protein S are more common among partners of patients than in the general population, both RDD subjects and partners of patients were considered as control subjects and all analyses were unmatched.…”

Association between the acquired free protein S deficiency in HIV‐infected patients with the lipid profile levels

“…Several environmental and inherited factors condition PS plasma levels, including lipid profile, variables associated with insulin resistance, oral contraceptive pills or hormone replacement therapy, sex, age and body mass index (BMI) [1][2][3][4]. Normally, approximately 30-40% of PS circulates freely in plasma and 60-70% is bound to C4b-binding protein (C4Bbp).…”

“…The PZdependent protease inhibitor in the presence of PZ causes fast inactivation of factor Xa. Recently, reduced circulating levels of PZ have been suggested to play a role in the occurrence of bleeding [2] and deep vein thrombosis [3,4], as well as primary aborts with unexplained early fetal loss [5]. However, these data have been disputed [6][7][8].…”