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    Oral Communication

    Pediatrics

    Clinical and Basic Science Insights Related to Neonatal Hemostasis and Neonatal Thrombosis

    OC 67.3 - Investigating biomarkers of bleeding in neonates and infants undergoing cardiac surgery with cardiopulmonary bypass using proteomics

    Tuesday, June 27, 2023
    15:15 – 15:30 ET
    Room: 518
    Session Available As: On-Demand

      Co-Author(s)

    • SV

      Suelyn Van Den Helm

      PhD Student
      Haematology Research, Murdoch Children's Research Institute
      Parkville, Victoria, Australia

      • Co-Author(s)

    • PD

      Paul Davies

      Consultant Anaesthetist
      Department of Anaesthesia and Pain Management, The Royal Children’s Hospital, Melbourne, Australia
      Melbourne, Victoria, Australia

    • SE

      Samantha Emery-Corbin

      Senior Research Officer
      Advanced Technology and Biology, Walter and Eliza Hall Institute, Melbourne, Australia
      Melbourne, Victoria, Australia

    • JY

      Jumana Yousef

      Bioinformatician/Statistician
      Advanced Technology and Biology, Walter and Eliza Hall Institute, Melbourne, Australia
      Melbourne, Victoria, Australia

    • SM

      Shannon Morrison

      Anaesthetist
      Department of Anaesthesia and Pain Management, Queensland Children's Hospital, Brisbane, Australia
      Brisbajne, Queensland, Australia

    • IK

      Igor Konstantinov

      Consultant Cardiothoracic Surgeon
      Department of Cardiac Surgery, The Royal Children's Hospital, Melbourne, Australia
      Melbourne, Victoria, Australia

    • BD

      Ben Davies

      Consultant Cardiac Surgeon
      Department of Cardiac Surgery, The Royal Children's Hospital, Melbourne, Australia
      Melbourne, Victoria, Australia

    • SH

      Stephen Horton

      Director of Perfusion
      Perfusion Department, The Royal Children's Hospital, Melbourne, Australia
      Melbourne, Victoria, Australia

    • Vera Ignjatovic, PhD (she/her/hers)

      Assistant Director for Translational Research
      Institute for Clinical and Translational Research, Johns Hopkins All Children's Hospital, St. Petersburg, USA
      St. Petersburg, Florida, United States

    • Paul Monagle, MD

      Professor
      Haematology Research, Murdoch Children's Research Institute
      Melbourne, Victoria, Australia

      • Presenting Author(s)

    • Chantal Attard, BSc (Hons), PhD (she/her/hers)

      Senior Research Officer
      Haematology Research, Murdoch Children's Research Institute
      Parkville, Victoria, Australia

    Background: Each year in Australia, approximately 3000 babies are born with congenital heart disease (CHD). Surgery for CHD frequently involves the use of cardiopulmonary bypass (CPB). Bleeding is a significant complication in babies that undergo surgery with CPB and is associated with increased risk of death.

    Aims: To identify biomarkers of bleeding in neonates and infants undergoing surgery for CHD with CPB.

    Methods: This study was approved by the Royal Children’s Hospital Human Research Ethics Committee and funded by the National Blood Authority, Australia. Parents/guardians provided written informed consent. Blood samples from babies ( < 1 year) undergoing CPB were collected at baseline (pre-CPB), pre-protamine (post-CPB), post-protamine, hourly post-protamine until leaving theatre, upon return to the paediatric intensive care unit (PICU) and the next morning in PICU. A pilot proteomic study using data-independent acquisition mass spectrometry (DIA-MS) was conducted on citrated plasma samples from 6 patients (out of 138 recruited in total), 3 who bled post-CPB (“bleeders” defined as requiring recombinant factor VII or prothrombin complex administration) and 3 who did not bleed (“non-bleeders”) (Table 1).

    Results: A total of 426 proteins were reproducibly identified in the 6 pilot patients. The protein profile changes over time in all patients and bleeders and non-bleeders cluster differently at most time points apart from pre-protamine (Figure 1). A non-redundant total of 129 proteins were differentially abundant between bleeders and non-bleeders at each time point and 175 significant proteins were identified in time course analysis as different between the groups.

    Conclusion(s): This is the first study using discovery proteomics to determine blood specific markers associated with bleeding. A number of proteins are associated with bleeding and further analysis of more patients is required. Differences in protein profiles of bleeders and non-bleeders already exist at baseline and could allow for early identification and prophylaxis of patients with increased risk of bleeding.

    Learning Objectives:

    • Upon completion, participants should be able to describe some of the effects on haemostasis that cardiopulmonary bypass has in neonates and infants undergoing cardiac surgery.
    • Upon completion, participants should be able to describe what proteomics is.
    • Upon completion, participants should be able to describe how proteomic analysis can be used in a clinical research setting.