Justyna Bartoszko1,2,3, Han Li4, John Fitzgerald5, Loretta T S Ho6, Cyril Serrick4, Walter H A Kahr7,8, Peter L Gross9, Keyvan Karkouti10,6,11,12,13. 1. Department of Anesthesia and Pain Management, Sinai Health System, Women's College Hospital, University Health Network, Toronto, ON, Canada. justyna.bartoszko@uhn.ca. 2. Department of Anesthesiology and Pain Medicine, University of Toronto, Toronto, ON, Canada. justyna.bartoszko@uhn.ca. 3. Department of Anesthesia and Pain Management, University Health Network, Toronto General Hospital, 200 Elizabeth Street, 3EN-464, Toronto, ON, M5G 2C4, Canada. justyna.bartoszko@uhn.ca. 4. Perfusion Services, University Health Network, Toronto, ON, Canada. 5. Department of Anaesthesia and Intensive Care, Beaumont Hospital, Dublin, Ireland. 6. Department of Anesthesiology and Pain Medicine, University of Toronto, Toronto, ON, Canada. 7. Departments of Paediatrics and Biochemistry, University of Toronto, Toronto, ON, Canada. 8. Division of Haematology/Oncology, Cell Biology Program, The Hospital for Sick Children, Toronto, ON, Canada. 9. Division of Hematology and Thromboembolism, Department of Medicine, McMaster University, Hamilton, ON, Canada. 10. Department of Anesthesia and Pain Management, Sinai Health System, Women's College Hospital, University Health Network, Toronto, ON, Canada. 11. Peter Munk Cardiac Centre, University Health Network, Toronto, ON, Canada. 12. Interdepartmental Division of Critical Care, Department of Medicine, University of Toronto, Toronto, ON, Canada. 13. Institute for Health Policy, Management, and Evaluation, University of Toronto, Toronto, ON, Canada.
Abstract
BACKGROUND: Cardiac surgery with cardiopulmonary bypass (CPB) is associated with coagulopathic bleeding. Impaired thrombin generation may be an important cause of coagulopathic bleeding but is poorly measured by existing hemostatic assays. We examined thrombin generation during cardiac surgery, using calibrated automated thrombography, and its association with bleeding outcomes. METHODS: We conducted a prospective observational study in 100 patients undergoing cardiac surgery with CPB. Calibrated automated thrombography parameters were expressed as a ratio of post-CPB values divided by pre-CPB values. The association of thrombin generation parameters for bleeding outcomes was compared with conventional tests of hemostasis, and the outcomes of patients with the most severe post-CPB impairment in thrombin generation (≥ 80% drop from baseline) were compared with the rest of the cohort. RESULTS: All 100 patients were included in the final analysis, with a mean age of 63 (12) yr, 31 (31%) female, and 94 (94%) undergoing bypass and/or valve surgery. Post-CPB, peak thrombin decreased by a median of 73% (interquartile range [IQR], 49-91%) (P < 0.001) and total thrombin generation, expressed as the endogenous thrombin potential (ETP), decreased 56% [IQR, 30-83%] (P < 0.001). In patients with ≥ 80% decrease in ETP, 21% required re-exploration for bleeding compared with 7% in the rest of the cohort (P = 0.04), and 48% required medical or surgical treatment for hemostasis compared with 27% in the rest of the cohort (P = 0.04). CONCLUSIONS: Thrombin generation is significantly impaired by CPB and associated with higher bleeding severity. Clinical studies aimed at the identification and treatment of patients with impaired thrombin generation are warranted.
BACKGROUND: Cardiac surgery with cardiopulmonary bypass (CPB) is associated with coagulopathic bleeding. Impaired thrombin generation may be an important cause of coagulopathic bleeding but is poorly measured by existing hemostatic assays. We examined thrombin generation during cardiac surgery, using calibrated automated thrombography, and its association with bleeding outcomes. METHODS: We conducted a prospective observational study in 100 patients undergoing cardiac surgery with CPB. Calibrated automated thrombography parameters were expressed as a ratio of post-CPB values divided by pre-CPB values. The association of thrombin generation parameters for bleeding outcomes was compared with conventional tests of hemostasis, and the outcomes of patients with the most severe post-CPB impairment in thrombin generation (≥ 80% drop from baseline) were compared with the rest of the cohort. RESULTS: All 100 patients were included in the final analysis, with a mean age of 63 (12) yr, 31 (31%) female, and 94 (94%) undergoing bypass and/or valve surgery. Post-CPB, peak thrombin decreased by a median of 73% (interquartile range [IQR], 49-91%) (P < 0.001) and total thrombin generation, expressed as the endogenous thrombin potential (ETP), decreased 56% [IQR, 30-83%] (P < 0.001). In patients with ≥ 80% decrease in ETP, 21% required re-exploration for bleeding compared with 7% in the rest of the cohort (P = 0.04), and 48% required medical or surgical treatment for hemostasis compared with 27% in the rest of the cohort (P = 0.04). CONCLUSIONS: Thrombin generation is significantly impaired by CPB and associated with higher bleeding severity. Clinical studies aimed at the identification and treatment of patients with impaired thrombin generation are warranted.
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