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Surgical Swine Model of Chronic Cardiac Ischemia Treated by Off-Pump Coronary Artery Bypass Graft Surgery
Published on: March 27, 2018
Thrombin generation and activation of the thrombomodulin protein C system in open heart surgery depend on the
I Welters1, T Menges, M Ballesteros
1Department of Anaesthesiology and Intensive Care Medicine, Justus-Liebig-University Giessen, Germany.
Insights
Coronary artery bypass grafting (CABG) patients show increased thrombin generation and endothelial damage markers during extracorporeal circulation (ECC) compared to aortic valve replacement (AVR) patients, suggesting a hypercoagulable state and potential thromboembolic risk.
Area of Science:
- Cardiovascular Surgery
- Hematology
- Coagulation Science
Background:
- Extracorporeal circulation (ECC) activates the coagulation system upon blood exposure to foreign surfaces.
- Arteriosclerotic patients exhibit heightened thrombin activation, elevated fibrinogen, and reduced protein C levels.
- Cardiac surgery necessitates understanding ECC's impact on hemostasis.
Purpose of the Study:
- To investigate how different cardiac diseases influence ECC-induced thrombin generation.
- To analyze the activation of the thrombomodulin-protein C system during ECC in cardiac surgery.
- To compare hemostatic changes between coronary artery bypass grafting (CABG) and aortic valve replacement (AVR) patients.
Main Methods:
- Studied 24 patients undergoing elective CABG or AVR.
- Collected blood samples pre-, during, and post-ECC, and postoperatively.
- Measured plasma concentrations of thrombin-antithrombin III-complex (TAT), prothrombin fragment F1+2, thrombomodulin, protein C, protein S, and modified antithrombin (ATM) using ELISA and nephelometry.
Main Results:
- Both CABG and AVR groups showed elevated TAT concentrations during ECC.
- CABG patients exhibited higher prothrombin fragment F1+2 and ATM levels during cardiopulmonary bypass.
- CABG patients had significantly increased plasma thrombomodulin and lower protein S levels, indicating endothelial damage and a hypercoagulable state.
Conclusions:
- CABG patients display a more pronounced hypercoagulable state during ECC compared to AVR patients.
- Elevated thrombomodulin and reduced protein S in CABG patients suggest significant endothelial activation.
- These distinct hemostatic changes in CABG patients may contribute to perioperative thromboembolic events.
Abstract:
The exposure of blood to foreign surfaces during extracorporeal circulation (ECC) leads to an activation of the coagulation system. In arteriosclerotic patients thrombin activation is increased and plasma fibrinogen is elevated, while protein C levels are reduced. In this study we investigated the influence of different cardiac diseases on ECC-induced thrombin generation and activation of the thrombomodulin-protein C system. Twenty-four patients undergoing either elective coronary artery bypass grafting (CABG) or elective aortic valve replacement (AVR) were included in the study. Blood samples were taken at different time intervals before, during and after ECC, and in the postoperative period. Plasma concentrations of thrombin-antithrombin III-complex (TAT), modified antithrombin (ATM), prothrombin fragment F1+2, free protein S, thrombomodulin, and protein C-antigen were determined by ELISA. Fibrinogen and antithrombin III levels were detected by nephelometry. Both groups were comparable with respect to biometric and ECC-related data. TAT concentrations were elevated in both groups after induction and increased during surgery (p<0.001). As a marker of thrombin generation levels of F1+2 were higher in the CABG group during cardiopulmonary bypass (p=0.003). In CABG patients ATM peaks were higher during ECC (p=0.0024). Significantly higher plasma thrombomodulin concentrations were found in CABG patients after induction (p<0.001), while protein S concentrations were higher in the AVR group (p=0.002). Protein C levels and antithrombin III concentrations did not differ between the groups. Patients undergoing CABG were found to have lower protein S levels and increased plasma thrombomodulin concentrations as markers of endothelial damage. In these patients contact activation and as a consequence thrombin generation takes place at a higher level, indicating a hypercoagulable state. Thromboembolic events in the perioperative period may be caused by different hemostatic changes in CABG patients.
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