Plasma Proteolytic Cascade Activation during Neonatal Cardiopulmonary Bypass Surgery. Thromb Haemost 2018 Sep;118(9):1545-1555
Date
08/08/2018Pubmed ID
30086574Pubmed Central ID
PMC6138520DOI
10.1055/s-0038-1667198Scopus ID
2-s2.0-85053427175 (requires institutional sign-in at Scopus site) 5 CitationsAbstract
BACKGROUND: Neonates undergoing cardiopulmonary bypass (CPB) surgery to correct congenital heart defects often experience excessive bleeding. Exposure of blood to artificial materials during CPB may activate coagulation, complement and inflammatory pathways. In addition, the surgical stress placed on the haemostatic system may result in cross-activation of other plasma proteolytic cascades, which could further complicate physiological responses to the surgical procedure and post-operative recovery. Plasma protease inhibitors undergo distinct conformational changes upon interaction with proteases, and, thereby, can serve as endogenous biosensors to identify activation of the different proteolytic cascades. We tested the hypothesis that changes in the concentration and conformation of protease inhibitors regulating plasma proteolytic cascades during neonatal CPB are associated with post-operative bleeding.
PATIENTS AND METHODS: Plasma samples from 44 neonates were obtained at four time points across the surgical procedure. Anti-thrombin, antitrypsin, anti-chymotrypsin, anti-plasmin, C1-inhibitor and tissue factor pathway inhibitor (TFPI) concentrations and conformations were evaluated by enzyme-linked immunosorbent assay, transverse urea gradient gel electrophoresis and sodium dodecyl sulphate-polyacrylamide gel electrophoresis.
RESULTS/CONCLUSION: The most striking changes were observed following heparin administration and were associated with the appearance of inactive forms of anti-thrombin and an increase in the plasma concentration of TFPI. Changes in anti-thrombin and TFPI remained evident throughout surgery and into the post-operative period but were not different between patients with or without post-operative bleeding. The concentration of antitrypsin decreased across surgery, but there was no significant accumulation of inactive conformations of any inhibitor besides anti-thrombin, indicating that widespread cross-activation of other plasma proteolytic cascades by coagulation proteases did not occur.
Author List
Maroney SA, Peterson JA, Zwifelhofer W, Martinez ND, Yan K, Bercovitz RS, Woods RK, Mast AEAuthors
Ronald K. Woods MD Professor in the Surgery department at Medical College of WisconsinKe Yan PhD Associate Professor in the Pediatrics department at Medical College of Wisconsin
MESH terms used to index this publication - Major topics in bold
AnticoagulantsBlood Coagulation
Cardiopulmonary Bypass
Female
Hemorrhage
Heparin
Humans
Infant, Newborn
Lipoproteins
Male
Peptide Hydrolases
Plasma
Postoperative Complications
Protein Binding
Thrombin
