Another point of view on the mechanism of thrombin generation during cardiopulmonary bypass: Role of tissue factor pathway inhibitor

Objective: To determine the role of tissue factor and tissue factor pathway inhibitor (TFPI) in coagulation activation during cardiopulmonary bypass ( CPB). Design: Prospective, observational study. Setting: Operating room in a city hospital. Participants: Thirty-one patients undergoing cardiac surgery. Measurements and Main Results: The plasma levels of tissue factor antigen ( tissue factor), total and free TFPId, several markers of thrombin generatio n (prothrombin fragment F1+2, thrombin antithrombin complex, and fibrinopep tide A), and heparin concentration were measured. Blood samples were obtain ed after induction of anesthesia (baseline level), before and after CPB, an d at the end of the surgery. Despite an average heparin concentration of 2. 9 +/- 0.2 IU/mL, markers of thrombin generation, fibrin formation and its d egradation (D-dimer) were observed during CPB. Significant increases of tot al and free TFPI levels (p < 0.0001) were found during CPB associated with lower tissue factor concentration (p < 0.0001) compared with the baseline v alues. Heparin concentration correlated with levels of total TFPI (r(2) = 0 .613, P < 0.0001) and free TFPI (r(2) = 0.689, p < 0.0001). Tissue factor c oncentration showed significant negative correlations with levels of total TFPI (r(2) = 0.128, p = 0.0003) and free TFPI (r(2) = 0.070, p = 0.0078). Conclusion: These data indicate that TFPI release by heparin probably has a n important role in the suppression of the tissue factor-dependent coagulat ion pathway during CPB. These changes occur along with ongoing thrombin gen eration and its activation. Either insufficient prevention of thrombin gene ration by TFPI or indirect activation of the intrinsic coagulation pathway occurs during CPB. Copyright (C) 2001 by W.B. Saunders Company.