Role of Omega-6 Fatty Acid Metabolism in Cardiac Surgery Postoperative Bleeding Risk

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.

Keywords: cardiac surgery; inflammation; metabolism; platelet; postoperative bleeding.

Figure 1.

Platelet count (A), variability in percentage (B), platelet mean volume (C), and platelet distribution width (D) of preoperative and 6- and 24-hr postoperative patients. Values are presented in median with interquartile range.

Figure 2.

A, Correlation of postoperative bleeding (mL) within the first postoperative 12 hr and preoperative quantification of arachidonic acid. B, Preoperative arachidonic acid levels between patients with (green) or without (red) a significant postoperative bleeding (defined by postoperative chest tube blood loss of more than 600 mL within 12 hr). C, Median postoperative chest tube blood within 12 hr according to arachidonic acid quantification.

Figure 3.

A, Postoperative transfusion rate considering preoperative arachidonic acid quantification and the reduction in percentage at postoperative 6 hr. B, Receiver operating characteristic curve based on the preoperative arachidonic acid measurements and represented by an area under the curve (AUC) of 0.73 indicating a satisfactory predictive ability. C, Correlation between human interleukin 6 levels and variability in arachidonic acid levels at 6 hr postoperative (percent change compared with preoperative levels).