title: Heparin and Protamine Titration Does Not Improve Haemostasis after Cardiac Surgery: A Prospective Randomized Study.
abstract: BACKGROUND
  Bleeding complications are common in cardiac surgery. Perioperative handling of heparin and protamine may influence the haemostasis. We hypothesized that heparin and protamine dosing based on individual titration curves would improve haemostasis in comparison to standard dosing.
  
  
  METHODS
  Sixty patients scheduled for first time elective coronary artery bypass grafting or valve surgery were included in a prospective randomized study. The patients were randomized to heparin and protamine dosing with Hepcon HMS Plus device or to standard weight and activated clotting time (ACT) based dosing. Blood samples were collected before and 10 minutes, 2 hours and 4 hours after cardiopulmonary bypass. Primary endpoint was endogenous thrombin potential in plasma 2 hours after surgery as assessed by calibrated automated thrombography. Secondary endpoints included total heparin and protamine doses, whole blood clot formation (thromboelastometry) and post-operative bleeding volume and transfusions. Heparin effect was assessed by measuring anti-Xa activity.
  
  
  RESULTS
  Endogenous thrombin potential and clot formation deteriorated in both groups after surgery without statistically significant intergroup difference. There were no significant differences between the groups in total heparin and protamine doses, heparin effect, or postoperative bleeding and transfusions at any time point. Significant inverse correlations between anti-Xa activity and endogenous thrombin potential were observed 10 min (r = -0.43, p = 0.001), 2 hours (r = -0.66, p<0.001) and 4 hours after surgery (r = -0.58, p<0.001).
  
  
  CONCLUSIONS
  In conclusion, the results suggest that perioperative heparin and protamine dosing based on individual titration curves does not improve haemostasis after cardiac surgery. Postoperative thrombin generation capacity correlates to residual heparin effect.
  
  
  BACKGROUND
  www.isrctn.com ISRCTN14201041.
authors.affiliation: Department of Medicine/Hematology and Coagulation Disorders, Sahlgrenska University Hospital, Gothenburg, Sweden.
authors.forename: Vladimir
authors.initials: V
authors.lastname: Radulovic
authors.affiliation: Department of Cardiothoracic Surgery, Sahlgrenska University Hospital, Gothenburg, Sweden.
authors.forename: Anna
authors.initials: A
authors.lastname: Laffin
authors.affiliation: AstraZeneca R&D, Mölndal, Sweden.
authors.forename: Kenny M
authors.initials: KM
authors.lastname: Hansson
authors.affiliation: Department of Cardiothoracic Surgery, Sahlgrenska University Hospital, Gothenburg, Sweden.
authors.forename: Erika
authors.initials: E
authors.lastname: Backlund
authors.affiliation: Department of Medicine/Hematology and Coagulation Disorders, Sahlgrenska University Hospital, Gothenburg, Sweden.
authors.forename: Fariba
authors.initials: F
authors.lastname: Baghaei
authors.affiliation: Department of Cardiothoracic Surgery, Sahlgrenska University Hospital, Gothenburg, Sweden; Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
authors.forename: Anders
authors.initials: A
authors.lastname: Jeppsson
mesh_terms: D000368:Aged; D000925:Anticoagulants / Q000494:pharmacology*; D001780:Blood Coagulation Tests; D016063:Blood Loss, Surgical / Q000517:prevention & control*; D058385:Cardiac Valve Annuloplasty; D001026:Coronary Artery Bypass; D004334:Drug Administration Schedule; D054796:Drug Dosage Calculations; D015951:Factor Xa / Q000378:metabolism; D005260:Female; D006487:Hemostasis / Q000187:drug effects*; D006493:Heparin / Q000494:pharmacology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D011479:Protamines / Q000494:pharmacology*; D013917:Thrombin / Q000378:metabolism
chemical_list: D000925:Anticoagulants; D011479:Protamines; D006493:Heparin; D013917:Thrombin; D015951:Factor Xa