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 TFPI, several markers of thrombin generation (prothrombin fragment F1+2, thrombin antithrombin complex, and fibrinopeptide A), and heparin concentration were measured. Blood samples were obtained after induction of anesthesia (baseline level), before and after CPB, and 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 degradation (D-dimer) were observed during CPB. Significant increases of total and free TFPI levels (p < 0.0001) were found during CPB associated with lower tissue factor concentration (p < 0.0001) compared with the baseline values. Heparin concentration correlated with levels of total TFPI (r2 = 0.613, p < 0.0001) and free TFPI (r2 = 0.689, p < 0.0001). Tissue factor concentration showed significant negative correlations with levels of total TFPI (r2 = 0.128, p = 0.0003) and free TFPI (r2 = 0.070, p = 0.0078). CONCLUSION These data indicate that TFPI release by heparin probably has an important role in the suppression of the tissue factor-dependent coagulation pathway during CPB. These changes occur along with ongoing thrombin generation and its activation. Either insufficient prevention of thrombin generation by TFPI or indirect activation of the intrinsic coagulation pathway occurs during CPB.

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