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Role of Omega-6 Fatty Acid Metabolism in Cardiac Surgery Postoperative Bleeding Risk
Tiago R Velho1,2, Ricardo Ferreira2,3, Katharina Willmann1
1Instituto Gulbenkian de Ciência, Oeiras, Portugal.
Insights
Cardiac surgery impairs platelet function, leading to bleeding. Preoperative arachidonic acid (AA) levels, not platelet count, may predict postoperative bleeding risk after cardiopulmonary bypass (CPB).
Area of Science:
- Cardiovascular Surgery
- Hematology
- Metabolomics
Background:
- Cardiac surgery often causes significant postoperative bleeding.
- Cardiopulmonary bypass (CPB) induces platelet dysfunction, affecting both platelet number and function.
- Platelet lipid metabolism is vital for function, but CPB-associated metabolic changes are poorly understood.
Purpose of the Study:
- To investigate the role of metabolic perturbations in platelet dysfunction following cardiac surgery.
- To explore the contribution of altered fatty acid metabolism to postoperative bleeding.
Main Methods:
- Prospective cohort study of 33 patients undergoing elective aortic valve replacement.
- Untargeted metabolomic analysis of platelet samples collected preoperatively and 6, 24 hours post-CPB.
- Comparison of metabolic profiles between patients with and without significant postoperative bleeding.
Main Results:
- A platelet metabolic signature involving fatty acid pathways was identified.
- Reduced arachidonic acid (AA) levels post-CPB correlated with increased bleeding and transfusion rates.
- Preoperative AA levels were inversely correlated with postoperative blood loss, independent of platelet count.
Conclusions:
- Inflammatory-related alterations in AA metabolism are characteristic of CPB-associated cardiac surgery.
- Preoperative AA levels may be a more reliable predictor of postoperative bleeding than platelet count.
- Targeting AA metabolism could offer new strategies for preventing bleeding after cardiac surgery.
Abstract:
Cardiac surgery is frequently associated with significant postoperative bleeding. Platelet-dysfunction is the main cardiopulmonary bypass (CPB)-induced hemostatic defect. Not only the number of platelets decreases, but also the remaining are functionally impaired. Although lipid metabolism is crucial for platelet function, little is known regarding platelet metabolic changes associated with CPB-dysfunction. Our aim is to explore possible contribution of metabolic perturbations for platelet dysfunction after cardiac surgery.
Design:
Prospective cohort study.
Setting:
Tertiary academic cardiothoracic-surgery ICU.
Patients:
Thirty-three patients submitted to elective surgical aortic valve replacement.
Interventions:
Samples from patients were collected at three time points (preoperative, 6- and 24-hr postoperative). Untargeted metabolic analysis using high-performance liquid chromatography-tandem mass spectrometry was performed to compare patients with significant postoperative bleeding with patients without hemorrhage. Principal component analyses, Wilcoxon matched-pairs signed-rank tests, adjusted to FDR, and pairwise comparison were used to identify pathways of interest. Enrichment and pathway metabolomic complemented the analyses.
Measurements And Main Results:
We identified a platelet-related signature based on an overrepresentation of changes in known fatty acid metabolism pathways involved in platelet function. We observed that arachidonic acid (AA) levels and other metabolites from the pathway were reduced at 6 and 24 hours, independently from antiagreggation therapy and platelet count. Concentrations of preoperative AA were inversely correlated with postoperative chest tube blood loss but were not correlated with platelet count in the preoperative, at 6 or at 24 hours. Patients with significant postoperative blood-loss had considerably lower values of AA and higher transfusion rates. Values of postoperative interleukin-6 were strongly correlated with AA variability.
Conclusions And Relevance:
Our observations suggest that an inflammatory-related perturbation of AA metabolism is a signature of cardiac surgery with CPB and that preoperative levels of AA may be more relevant than platelet count to anticipate and prevent postoperative blood loss in patients submitted to cardiac surgery with CPB.
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