title: Effect of cardiopulmonary bypass on thrombin generation and protein C pathway.
abstract: OBJECTIVE
  The purpose of this study was to evaluate the mechanisms of cardiopulmonary bypass (CPB)-induced dysregulation between thrombin and its regulatory anticoagulant activated protein C (APC).
  
  
  METHODS
  A prospective observational cohort study.
  
  
  METHODS
  A tertiary care university hospital and associated research laboratory.
  
  
  METHODS
  Twenty patients undergoing elective coronary artery bypass surgery with (n = 10) or without CPB (n = 10).
  
  
  METHODS
  Blood samples were collected at 7 time points: preinduction; after heparin; 1 hour after the institution of CPB (or the completion of distal anastomoses in off-CPB group); after protamine; and at 0, 4, and 18 hours in the Intensive care unit (ICU). Samples were analyzed for prothrombin fragments (F1+2), thrombin-antithrombin complexes, protein C (PC), APC, soluble thrombomodulin (sTM), and soluble endothelial protein C receptor (sEPCR).
  
  
  RESULTS
  F1+2 levels increased significantly 1 hour after the initiation of CPB in comparison with baseline (2.7 ± 0.5 v 0.5 ± 0.2 nmol/L, p < 0.001) (mean ± standard deviation) and remained elevated until 4 hours after ICU admission (p < 0.001). In contrast, APC levels did not show any significant changes over time in either group. sEPCR, sTM, and PC levels did not change during CPB although sEPCR decreased significantly after the termination of CPB compared with baseline in the CPB group.
  
  
  CONCLUSIONS
  Exposure to CPB is associated with a distinct thrombin surge that continues postoperatively for 4 hours. The impaired ability to generate APC reflects a complex process that is not associated with increased levels of sEPCR and thrombomodulin during CPB. Further studies are required to evaluate the regulation of the host APC response in cardiac surgery.
authors: Centre for Critical Illness Research, Lawson Health Research Institute, London Health Sciences Centre, London, Ontario, Canada. ravi.taneja@lhsc.on.ca
authors: Ravi
authors: R
authors: Taneja
authors: Patricia L
authors: PL
authors: Liaw
authors: Samer
authors: S
authors: Al Ghazaly
authors: Fran
authors: F
authors: Priestap
authors: John M
authors: JM
authors: Murkin
authors: Claudio M
authors: CM
authors: Martin
mesh_terms: D000368:Aged; D002315:Cardiopulmonary Bypass / Q000009:adverse effects; D015331:Cohort Studies; D004730:Endothelium, Vascular / Q000378:metabolism / Q000502:physiology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011183:Postoperative Complications / Q000097:blood* / Q000453:epidemiology; D011446:Prospective Studies; D011486:Protein C / Q000378:metabolism / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*; D013917:Thrombin / Q000096:biosynthesis* / Q000378:metabolism; D016896:Treatment Outcome; D015854:Up-Regulation / Q000502:physiology
chemical_list: D011486:Protein C; D013917:Thrombin