Serum from hemodialysis patients inhibits basal and cytokine-stimulated tissue factor expression in vitro.

Hemorrhagic complications are common among hemodialysis (HD) patients. The mechanisms by which HD perturbs the coagulation cascade are still being defined. This study evaluated the influence of HD serum on cellular expression of tissue factor (TF), a procoagulant membrane-associated protein that is a pivotal regulator of blood coagulation. Serum was collected immediately before dialysis and 15, 30, and 180 min into HD using polysulfone membranes. Serum was then assessed for its ability to influence basal and cytokine-stimulated TF activity in human umbilical vein endothelial cells and ECV304 cells. Predialysis serum did not influence basal levels of TF activity. HD was associated with the appearance of a serum factor that suppressed basal TF activity (TF units/microg protein: predialysis serum 8.2 +/- 0.9; 180-min dialysis serum 4.9 +/- 0.6; P < 0.05) and TF activity induced by the cytokine tumor necrosis factor-alpha (TNFalpha) (TF units/microg protein: TNFalpha alone 15.9 +/- 0.7; TNFalpha + 180-min dialysis serum 5.9 +/- 0.9; P < 0.01). This response was not mimicked by heparin, suggesting production of an endogenous inhibitor of TF activity during HD. Dialysis was associated with a striking increase in circulating levels of tissue factor pathway inhibitor (TFPI), a physiologic inhibitor of the TF/VIIa complex. The lack of temporal correlation between TFPI levels and suppression of TF activity, however, suggested the presence of additional TFPI independent pathway(s) for modulation of TF activity. Dialysis-related suppression of TF expression may contribute to hemorrhagic complications in HD patients.