title: Measurement of thrombin generation intra-operatively and its association with bleeding tendency after cardiac surgery.
abstract: BACKGROUND
  Patients undergoing cardiac surgery with cardiopulmonary bypass (CPB) are susceptible to haemostatic disturbances. Monitoring the haemostatic capacity by conventional clotting tests is challenging.
  
  
  METHODS
  Thrombin generation (TG) by Calibrated Automated Thrombography, clotting tests and tissue factor pathway inhibitor (TFPI) measurements were performed to describe the relationship between haemostatic changes and alterations in these tests. Blood samples were collected before, during and after CPB. Furthermore, it was investigated whether TG measured intraoperatively, is associated with increased risk of bleeding postoperatively.
  
  
  RESULTS
  TG diminished significantly (p<0.01) after heparinization in the presence and absence of platelets (37% and 50%) compared to baseline. After the start of CPB, TG elevated and persisted till the end of surgery but remained lower than preoperatively. Activated clotting time increased after heparinization and after the start of bypass compared to baseline (400% and 500%). Anti-FXa activity reduced on the start of CPB compared to the level after heparinization, to almost the baseline value following protamine reversal of heparin. The plasma levels of total and free TFPI elevated 9 and 14 fold during bypass and remained after protamine administration higher than preoperatively. Plasma D-dimer levels reduced (p<0.01) when bypass started. However, a marked elevation was observed in the following time points. TG in platelet-rich plasma measured after heparinization and after the start of CPB associated (p<0.05) with postoperative blood loss.
  
  
  CONCLUSIONS
  TG can be determined during CPB despite the high heparinization level, it reflects the haemostatic capacity better than clotting-based assays and might better predict bleeding when performed intraoperatively.
authors.affiliation: Maastricht University Medical Center(+), Cardiovascular Research Institute Maastricht. Electronic address: yvonne.bosch@mumc.nl.
authors.forename: Yvonne P J
authors.initials: YP
authors.lastname: Bosch
authors.affiliation: Maastricht University Medical Center(+), Cardiovascular Research Institute Maastricht.
authors.forename: Raed
authors.initials: R
authors.lastname: Al Dieri
authors.affiliation: Maastricht University Medical Center(+), Cardiovascular Research Institute Maastricht.
authors.forename: Hugo
authors.initials: H
authors.lastname: ten Cate
authors.affiliation: Maastricht University Medical Center(+), Cardiovascular Research Institute Maastricht.
authors.forename: Patty J
authors.initials: PJ
authors.lastname: Nelemans
authors.affiliation: Maastricht University Medical Center(+), Cardiovascular Research Institute Maastricht.
authors.forename: Saartje
authors.initials: S
authors.lastname: Bloemen
authors.affiliation: Maastricht University Medical Center(+), Cardiovascular Research Institute Maastricht.
authors.forename: Bas
authors.initials: B
authors.lastname: de Laat
authors.affiliation: Maastricht University Medical Center(+), Cardiovascular Research Institute Maastricht.
authors.forename: Coenraad
authors.initials: C
authors.lastname: Hemker
authors.affiliation: Maastricht University Medical Center(+), Cardiovascular Research Institute Maastricht.
authors.forename: Patrick W
authors.initials: PW
authors.lastname: Weerwind
authors.affiliation: Maastricht University Medical Center(+), Cardiovascular Research Institute Maastricht.
authors.forename: Jos G
authors.initials: JG
authors.lastname: Maessen
authors.affiliation: Maastricht University Medical Center(+), Cardiovascular Research Institute Maastricht.
authors.forename: Baheramsjah
authors.initials: B
authors.lastname: Mochtar
mesh_terms: D000368:Aged; D000925:Anticoagulants / Q000008:administration & dosage*; D001778:Blood Coagulation Disorders / Q000097:blood / Q000188:drug therapy / Q000209:etiology; D006348:Cardiac Surgical Procedures / Q000009:adverse effects / Q000379:methods*; D002315:Cardiopulmonary Bypass / Q000009:adverse effects / Q000379:methods*; D006493:Heparin / Q000008:administration & dosage*; D006801:Humans; D007430:Intraoperative Care / Q000379:methods; D008297:Male; D019106:Postoperative Hemorrhage / Q000097:blood; D013917:Thrombin / Q000032:analysis* / Q000096:biosynthesis*
chemical_list: D000925:Anticoagulants; D006493:Heparin; D013917:Thrombin
keywords: blood loss; cardiopulmonary bypass; heparinization; monitoring of haemostasis; thrombin generation