Postoperative reduction in thrombin generation induced by elevated levels of tissue factor pathway inhibitor in cardiac surgery: a prospective observational study

PURPOSE: Tissue factor pathway inhibitor (TFPI) is an intrinsic anticoagulant factor, and its plasma concentration is elevated by heparin administration. Because several hours are required to return to normal range after heparin reversal, we investigated the role of TFPI in the inhibition of thrombin generation (TG) in patients undergoing cardiac surgery. METHODS: Blood samples were collected from adult patients undergoing cardiac surgery with cardiopulmonary bypass (CPB) before, at the end of, and 1 day after surgery. Plasma concentration of TFPI, peak height of the TG assay (peak TG), and whole blood coagulation time by dielectric blood coagulometry using a Russell's viper venom cartridge system were evaluated. Nonparametric correlation was evaluated using Spearman's method, and time-dependent change was analyzed using repeated measures analysis of variance. RESULTS: The plasma concentration of TFPI was higher (54 [47-60] ng/mL vs. 18 [13-27] ng/mL; P < 0.001) and the peak TG value was lower (98.1 [48.9-148] nM vs. 268 [244-309]; P < 0.001) at the end of surgery than before surgery. Plasma TFPI concentration showed a positive correlation with whole blood coagulation time as measured by dielectric blood coagulometry (Rs = 0.643) and a negative correlation with peak TG (Rs = - 0.624). Anti-TFPI antibody neutralized reduction in peak TG. CONCLUSIONS: In patients undergoing cardiac surgery using CPB, the increase in plasma TFPI concentration at the end of surgery causes a reduction in TG and impairment of whole blood coagulation via a mechanism that includes inhibition of factor Xa activity.