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Pericardial blood activates the extrinsic coagulation pathway during clinical cardiopulmonary bypass
J H Chung1, N Gikakis, A K Rao
1Department of Surgery, School of Medicine, University of Pennyslvania, Philadelphia 19104, USA.
Insights
During cardiac surgery, the surgical wound activates the extrinsic coagulation pathway via tissue factor (TF) expression on monocytes. This promotes thrombus formation during cardiopulmonary bypass (CPB).
Area of Science:
- Cardiovascular Surgery
- Hemostasis and Thrombosis
- Coagulation Cascade
Background:
- Coagulation during cardiopulmonary bypass (CPB) is traditionally linked to the contact system and intrinsic pathway.
- Emerging research suggests a role for the extrinsic coagulation pathway in cardiac surgery.
- This study investigates the hypothesis that surgical wounds activate the extrinsic pathway during CPB.
Purpose of the Study:
- To investigate the activation of the extrinsic coagulation pathway during cardiac surgery.
- To determine the role of tissue factor (TF) expression in this process.
- To assess thrombin formation within the surgical wound environment.
Main Methods:
- Assayed blood samples from 20 cardiac surgery patients for TF expression, F1.2, and factor VII/VIIa concentrations.
- Measured TF expression on peripheral blood mononuclear cells (PBMCs) and monocytes.
- Analyzed blood from the pericardial cavity and perfusate during CPB.
Main Results:
- PBMC TF expression increased post-incision and after CPB initiation, particularly in monocytes adhering to the circuit.
- Elevated TF levels were found in pericardial blood compared to perfusate.
- F1.2 and factor VIIa concentrations increased progressively in pericardial blood during and after CPB.
Conclusions:
- Direct evidence supports TF expression and extrinsic pathway activation in the surgical wound.
- Pericardial blood contributes to thrombus formation during open-heart surgery.
- TF expression by circulating and adherent monocytes significantly promotes thrombosis during CPB.
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.