Nathan Clendenen1, Ashley Tollefson1,2, Monika Dzieciatkowska3, Alice Cambiaghi4, Manuela Ferrario4, Miranda Kroehl5, Anirban Banerjee6, Angelo D'Alessandro3, Kirk C Hansen3, Nathaen Weitzel1. 1. Department of Anesthesiology, University of Colorado Denver, Aurora, CO, USA. 2. Medical School, University of Minnesota, Minneapolis, MN, USA. 3. Department of Biochemistry and Molecular Genetics, University of Colorado Denver, Aurora, CO, USA. 4. Politecnico di Milano, Milan, Italy. 5. Department of Biostatistics and Informatics, University of Colorado Denver, Aurora, CO, USA. 6. Department of Surgery, University of Colorado Denver, Aurora, CO, USA.
Abstract
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.
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 highbleeding 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.
Authors: Matthew R Russell; Brahim Achour; Edward A Mckenzie; Ruth Lopez; Matthew D Harwood; Amin Rostami-Hodjegan; Jill Barber Journal: J Proteome Res Date: 2013-10-31 Impact factor: 4.466
Authors: Michael C Christensen; Stephan Krapf; Angela Kempel; Christian von Heymann Journal: J Thorac Cardiovasc Surg Date: 2009-04-19 Impact factor: 5.209
Authors: Klaus Görlinger; Linda Shore-Lesserson; Daniel Dirkmann; Alexander A Hanke; Niels Rahe-Meyer; Kenichi A Tanaka Journal: J Cardiothorac Vasc Anesth Date: 2013-08 Impact factor: 2.628
Authors: Monika Dzieciatkowska; Angelo D'Alessandro; Ernest E Moore; Max Wohlauer; Anirban Banerjee; Christopher C Silliman; Kirk C Hansen Journal: Shock Date: 2014-12 Impact factor: 3.454
Authors: Julie M Pratt; Deborah M Simpson; Mary K Doherty; Jenny Rivers; Simon J Gaskell; Robert J Beynon Journal: Nat Protoc Date: 2006 Impact factor: 13.491
Authors: Tamara G Fong; Noel Y Chan; Simon T Dillon; Wenxiao Zhou; Bridget Tripp; Long H Ngo; Hasan H Otu; Sharon K Inouye; Sarinnapha M Vasunilashorn; Zara Cooper; Zhongcong Xie; Edward R Marcantonio; Towia A Libermann Journal: Ann Surg Date: 2021-04-01 Impact factor: 12.969