BACKGROUND: Coagulation during cardiopulmonary bypass (CPB) traditionally has been attributed to activation of the contact system of plasma proteins and the intrinsic coagulation pathway by blood contact with negatively charged surfaces not lined by endothelium. Recent studies have focused on the possible role of the extrinsic coagulation pathway during cardiac surgery. We postulated that the wound activates the extrinsic coagulation pathway during CPB by producing procoagulant cells and enzymes that enter the general circulation. METHODS AND RESULTS: Blood samples taken from 20 consenting patients who had elective cardiac surgery were assayed for peripheral blood mononuclear cell tissue factor (TF) expression, plasma F1.2, and factor VII and VIIa concentrations. Peripheral blood mononuclear cell TF expression increased in the perfusate after the surgical incision and after CPB was started and in monocytes that adhered to the perfusion circuit. TF on circulating monocytes, however, did not continue to rise during CPB. Peripheral blood mononuclear cell TF was elevated in cells isolated directly from blood in the pericardial cavity and was twice that detected in simultaneous samples from the perfusate (P < .05). F1.2 levels were highest in pericardial blood and increased progressively during CPB. Plasma factor VIIa concentrations, corrected for hemodilution, and ratios of factor VIIa to factor VII were highest in pericardial samples (P < .05) and increased progressively during and immediately after CPB. Pericardial biopsies obtained before and after CPB in 7 patients did not show TF expression by mesothelial cells. CONCLUSIONS: These data provide direct evidence of TF expression, activation of the extrinsic coagulation pathway, and thrombin formation in the surgical wound. Addition of pericardial blood to the perfusate and expression of TF by both circulating and adherent monocytes strongly promote thrombus formation during open heart surgery.
BACKGROUND: Coagulation during cardiopulmonary bypass (CPB) traditionally has been attributed to activation of the contact system of plasma proteins and the intrinsic coagulation pathway by blood contact with negatively charged surfaces not lined by endothelium. Recent studies have focused on the possible role of the extrinsic coagulation pathway during cardiac surgery. We postulated that the wound activates the extrinsic coagulation pathway during CPB by producing procoagulant cells and enzymes that enter the general circulation. METHODS AND RESULTS: Blood samples taken from 20 consenting patients who had elective cardiac surgery were assayed for peripheral blood mononuclear cell tissue factor (TF) expression, plasma F1.2, and factor VII and VIIa concentrations. Peripheral blood mononuclear cell TF expression increased in the perfusate after the surgical incision and after CPB was started and in monocytes that adhered to the perfusion circuit. TF on circulating monocytes, however, did not continue to rise during CPB. Peripheral blood mononuclear cell TF was elevated in cells isolated directly from blood in the pericardial cavity and was twice that detected in simultaneous samples from the perfusate (P < .05). F1.2 levels were highest in pericardial blood and increased progressively during CPB. Plasma factor VIIa concentrations, corrected for hemodilution, and ratios of factor VIIa to factor VII were highest in pericardial samples (P < .05) and increased progressively during and immediately after CPB. Pericardial biopsies obtained before and after CPB in 7 patients did not show TF expression by mesothelial cells. CONCLUSIONS: These data provide direct evidence of TF expression, activation of the extrinsic coagulation pathway, and thrombin formation in the surgical wound. Addition of pericardial blood to the perfusate and expression of TF by both circulating and adherent monocytes strongly promote thrombus formation during open heart surgery.
Authors: Nazish K Hashmi; Kamrouz Ghadimi; Amudan J Srinivasan; Yi-Ju Li; Robert D Raiff; Jeffrey G Gaca; Adam G Root; Yaron D Barac; Thomas L Ortel; Jerrold H Levy; Ian J Welsby Journal: Vox Sang Date: 2019-04-02 Impact factor: 2.144