Abstract
<jats:p>Nephrotic syndrome (NS) is associated with a significantly increased risk of thromboembolic complications resulting from profound disturbances of the hemostatic system. One of the central mechanisms underlying this hypercoagulable state is the imbalance between procoagulant and anticoagulant factors, particularly the depletion of natural anticoagulants such as antithrombin III (AT-III), protein C, and protein S. These proteins play a crucial physiological role in regulating coagulation and preventing excessive thrombin generation. A deficiency in these factors can promote the emergence of a hypercoagulable (prothrombotic) state that is frequently seen in patients with NS. This study was designed to evaluate the concentrations of physiological anticoagulants in patients with NS and to investigate their association with laboratory markers of hypercoagulability and disease severity. The cross-sectional study included 76 patients with primary glomerulonephritis (GN) accompanied by NS who were treated between 2022 and 2024, as well as a control group of 40 apparently healthy individuals. Hemostatic parameters were assessed using chromogenic and clot-based functional assays, and statistical analysis included correlation and multivariable regression models. The results demonstrated clear evidence of coagulation system activation in patients with NS. Levels of D-dimer and fibrinogen were significantly higher compared with the control group, reflecting increased thrombin generation and fibrin turnover. At the same time, significant reductions in the activity of natural anticoagulants were observed. AT-III levels were markedly decreased in patients with NS, and similar reductions were detected for protein C and free protein S. Correlation analysis revealed that AT-III showed the strongest associations with markers of NS activity and hypercoagulability. AT-III levels demonstrated a positive correlation with serum albumin and negative correlations with proteinuria, D-dimer, and fibrinogen. These findings suggest that both the severity of NS and the activation of coagulation pathways contribute to depletion of endogenous anticoagulant mechanisms. Multivariable regression analysis identified serum albumin and D-dimer levels as independent predictors of reduced AT-III activity. Hypoalbuminemia, reflecting urinary protein loss and disease severity, was strongly associated with decreased AT-III levels, while elevated D-dimer indicated ongoing activation of the coagulation cascade. Overall, the study demonstrates that nephrotic syndrome is characterized by a pronounced prothrombotic hemostatic profile involving both activation of coagulation and depletion of natural anticoagulants. Among the studied parameters, AT-III deficiency appears to represent the most prominent disturbance and may play a key role in the development of hypercoagulability in patients with NS. These findings highlight the potential clinical importance of assessing natural anticoagulant levels as biomarkers of thrombotic risk and may contribute to improved risk stratification and individualized prophylactic anticoagulation strategies in patients with NS.</jats:p>