Correlation of pre-operative plasma protein concentrations in cardiac surgery patients with bleeding outcomes using a targeted quantitative proteomics approach

Purpose: Despite recent advancements in the use of thrombelastography (TEG) in the surgical setting, adequate technology to accurately predict bleeding phenotypes for patients undergoing cardiopulmonary bypass on the basis of non-mechanical parameters is lacking. While basic science and translational studies have provided key mechanistic insights about the protein components of coagulation cascades and regulatory mediators of hemostasis and fibrinolysis, targeted protein assays are still missing and the association of protein profiles to bleeding phenotypes and TEG readouts have yet to be discovered. Objective: To identify protein biomarkers of bleeding phenotypes of cardiopulmonary bypass patients in pre-operative plasma. Experimental design: We applied a targeted proteomics approach to quantify 123 plasma proteins from 23 patients undergoing cardiopulmonary bypass (CPB) and sternotomy. We then correlated these measurements to bleeding outcomes and TEG parameters, associated with speed of clot formation and strength. Results: In this pilot study, we demonstrate the feasibility of protein quantitation as a viable strategy to predict low versus high bleeding phenotypes (loss of < or > than 20% of estimated blood volume, calculated as 70 mL/kg for BMI<29.9, 60 mL/kg for BMI = 30-39.9, and 50 mL/kg for BMI>40. Statistical elaborations highlighted a core set of proteins showing significant correlations to either total blood loss or TEG R/MA parameters. Conclusion and clinical relevance: Though prospective verification and validation in larger cohorts will be necessary, this report suggests a potential for targeted quantitative proteomics of pre-operative plasma protein concentrations in the prediction of estimated blood loss following CPB.