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: 1.09-10.06 and OR: 8.61, 95% CI: 1.07-69.04, respectively). Body mass index ≥ 25 kg/m2 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.