title: Ex vivo addition of fibrinogen concentrate improves the fibrin network structure in plasma samples taken during liver transplantation.
abstract: BACKGROUND
  Optimal hemostatic management during orthotopic liver transplantation (OLT) remains a challenge. The cause of bleeding during OLT is multifactorial, and may include hemostatic imbalance. Fibrinogen concentrates are increasingly being used to control perioperative bleeding during OLT. However, administration is based on arbitrary thresholds of fibrinogen levels. Importantly, studies on fibrin clot structure during OLT are lacking.
  
  
  OBJECTIVE
  We determined the hemostatic efficacy of fibrinogen concentrate in correcting the fibrin structure.
  
  
  METHODS
  Plasma samples taken at various times during OLT from 15 patients and 15 healthy controls were spiked with 1 g L(-1) fibrinogen concentrate or saline. Turbidity, fibrin fiber density and permeability of the fibrin clots were assessed.
  
  
  RESULTS
  Clotting rate and turbidity were significantly decreased at the start of surgery, and decreased even further during surgery. Addition of fibrinogen significantly increased the clotting rate and turbidity at all time points, but did not normalize it. Fibrin density was significantly reduced after reperfusion as compared with the density at the start of surgery and in healthy controls. Fibrin density improved significantly after addition of fibrinogen in samples taken at the start of surgery and after reperfusion. The severely impaired polymerization and decreased density after reperfusion were accompanied by significantly increased permeability of the clot as compared with the start of surgery and in controls, which was completely restored after addition of fibrinogen.
  
  
  CONCLUSIONS
  Ex vivo addition of fibrinogen concentrate during OLT substantially improves the structural properties of the fibrin clot, which, particularly after reperfusion, shows hypocoagulable features. These data support the use of fibrinogen concentrate to control bleeding complications during OLT.
authors.affiliation: Surgical Research Laboratory, Department of Surgery, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.
authors.forename: D J
authors.initials: DJ
authors.lastname: Groeneveld
authors.affiliation: Surgical Research Laboratory, Department of Surgery, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.
authors.forename: J
authors.initials: J
authors.lastname: Adelmeijer
authors.affiliation: Surgical Research Laboratory, Department of Surgery, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.
authors.forename: G C G
authors.initials: GC
authors.lastname: Hugenholtz
authors.affiliation: Thrombosis Research Group, Division of Cardiovascular and Diabetes Research, Multidisciplinary Cardiovascular Research Centre and Leeds Institute for Cardiovascular and Metabolic Medicine, School of Medicine, University of Leeds, Leeds, UK.
authors.forename: R A S
authors.initials: RA
authors.lastname: Ariëns
authors.affiliation: Section of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.
authors.forename: R J
authors.initials: RJ
authors.lastname: Porte
authors.affiliation: Surgical Research Laboratory, Department of Surgery, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.|Section of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.
authors.forename: T
authors.initials: T
authors.lastname: Lisman
mesh_terms: D000328:Adult; D000368:Aged; D001777:Blood Coagulation / Q000187:drug effects*; D001780:Blood Coagulation Tests; D016063:Blood Loss, Surgical / Q000517:prevention & control*; D016022:Case-Control Studies; D005176:Factor XIII / Q000378:metabolism; D005260:Female; D005337:Fibrin / Q000737:chemistry / Q000378:metabolism*; D005340:Fibrinogen / Q000494:pharmacology*; D006490:Hemostatics / Q000494:pharmacology*; D006801:Humans; D016031:Liver Transplantation / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D010539:Permeability; D058105:Polymerization; D016062:Porosity; D013997:Time Factors
chemical_list: D006490:Hemostatics; D005337:Fibrin; D005340:Fibrinogen; D005176:Factor XIII
keywords: blood loss, surgical; fibrin; fibrinogen; hemostasis; liver transplantation