Determinants of Elevated Levels of Natural Anticoagulants in Healthy Subjects

Abstract

Background. The levels of protein C (PC), free protein S (PS) and antithrombin (AT) are evaluated during thrombophilia screening to exclude their deficiencies. Objectives. The aim of this study was to investigate factors which determine the elevated levels of natural plasma anticoagulants in healthy individuals. Material and Methods. The PC activity and antigen, free PS antigen and AT activity together with hematological, biochemical, genetic and immunological laboratory tests were assessed in 130 healthy adults (63 males) aged 20-60 (median 41) years. Individuals with personal or family history of cardiovascular diseases and venous thromboembolism were ineligible. Results. The functionally active PC measured by chromogenic assay (values above 140%) was observed in 14 (11%) of subjects, while the PC antigen determined using the enzyme-linked immunosorbent assay (ELISA) was elevated in 5 (4%) of these patients. Free PS measured by immunoturbidimetry and ELISA was increased in 9 (7%) subjects (values above 139% in men and 114% for women) and in 6 (5%) patients (values above 130% in men and 111% for women), respectively. The AT activity above 118% was found in 5 (4%) subjects measured using chromogenic assay. None of the individuals had any deficiency of natural anticoagulants. Increased C-reactive protein (CRP) > 3.0 mg/L was associated with elevated PC activity (odd ratio [OR]: 11.14, 95% confidence interval [CI] 1.67-74.23). Increased free PS assessed by immunoturbidimetric assay and PC activity were associated with hypercholesterolemia (OR: 3.57, 95% CI: 1. respectively). Body mass index ≥ 25 kg/m 2 was independently associated with elevated PC activity (OR: 3.42, 95% CI: 1.01-11.52). No risk factors for elevated AT activity were identified. Conclusions. Apart from hypercholesterolemia and overweight, increased serum CRP is associated with elevated PC activity in healthy adults. We confirmed that there are differences in the proportions of subjects with elevated PC and PS depending on the assay used (Adv Clin Exp Med 2015, 24, 5, 791-800).

Thrombophilia: Women-Specific Reference Ranges Can Prevent Misdiagnosis in Women

“…Our finding that reference ranges are different in men and women is in line with the literature as previously reported data consistently show that sex has an influence on coagulation factors (16,18,21,24,25). With this present study, we concur with the suggestion of Lowe et al (21) that sex specific reference values at least should be considered in the diagnosis of congenital thrombophilias as a significant difference was seen in our study group.…”

Sex-specific associations between serum lipids and hemostatic factors: the cross-sectional population-based KORA-fit study

“…Protein C and its cofactor protein S are vitamin K-dependent coagulation inhibitors and play an important role in fibrinolytic processes [ 22 ]. In both sexes, these two coagulation factors showed similar associations with total cholesterol, LDL-c, and non-HDL-c; TGs were associated with both coagulation inhibitors in men, but in women, they were only related to protein C. A positive correlation of protein C with LDL-c was also found in the ARIC Study [ 23 ], and in a Polish study, protein C activity was associated with hypercholesterolemia [ 24 ]. Women had higher protein C activity than men, and protein S activity was significantly higher in men.…”

“…A Polish study including a random sample of community-dwelling older individuals also did not find an association between AT III activity and total cholesterol and LDL-c [ 29 ]. In addition, total cholesterol was not associated with AT III in a study on 130 healthy adults aged 20–60 years from Poland [ 24 ].…”

“…Prior studies observed possible effects of dyslipidemia on the coagulation system [ 23 , 24 , 27 , 28 , 30 – 35 ]. The present study found that sex is a moderator responsible for different effects in men and women regarding the relationships between lipid concentrations and coagulation factors.…”

Effect of pulmonary tuberculosis on natural anticoagulant activity in therapy-naïve Ghanaian adults; a case-control study

“…Furthermore, Kager et al [15] explained the anomaly in PS as been because, the majority of PS in the systemic circulation is bound to C4b, a complement factor that increases greatly in TB and therefore the reduced concentration of unbound protein S is justi ed to be the result of a rise in systemic C4b that occurs in TB patients. Similar to PC, PS is a vitamin K-dependent protein synthesized primarily within liver cells [33,34], as a result, altered function of the liver will impair its production. Also, more than half (53.3%) of our cases had recent or past history of alcoholism, a situation which can cause alcoholinduced liver in ammation and damage and consequently de ciency in protein S. This may have contributed to the low activity of protein S observed among PTB cases in this study.…”