Effect of Antithrombin Leakage From Hemodialysis Therapy on Antithrombin Hemodynamics

Introduction Hemodialysis (HD) therapy is a crucial treatment for patients with renal failure but can impact the hemodynamics of antithrombin (AT), a protein essential for regulating hemostasis and preventing thrombosis. Reduced AT activity can lead to thrombus formation at unusual sites and increase the risk of recurrent venous thromboembolism. The loss of AT during HD or hemodiafiltration (HDF) through leakage or adsorption onto dialysis membranes has not been fully investigated, and its effects on AT hemodynamics remain unclear. We aimed to elucidate the mechanisms underlying AT activity reduction due to dialysis, with the goal of developing dialysis protocols that preserve AT activity and reduce the risk of vascular access-related thrombosis. Methods AT activity and antigen levels were measured before and after dialysis therapy in 24 patients undergoing maintenance dialysis at Itaya Clinic (HD, 12; HDF, 12). AT antigen levels in dialysis effluent were also measured to analyze the effects of dialysis on AT hemodynamics. Additionally, immunofluorescence staining of dialysis membranes was used to semi-quantitatively assess the amount of AT adsorbed onto the membrane. Results AT activity and antigen levels in patients undergoing HD were significantly lower than those in healthy participants but increased following dialysis. A negative correlation was found between dialysis vintage (history of heparin use) and predialysis AT activity. AT leakage and adsorption were significantly greater with HDF than with HD. However, no correlation was observed between AT leakage and activity or antigen levels before and after dialysis. Conclusions AT activity and antigen levels were decreased in patients on HD, with long-term heparin use suggested as a contributing factor. Additionally, AT leakage was observed during HDF therapy, indicating that dialysis-related AT leakage may contribute to decreased AT activity and antigen levels. Therefore, regular measurement of AT activity is recommended for patients with HD. If AT activity decreases, treatment adjustments, such as switching to HD therapies that minimize AT leakage and adsorption, should be considered.