title: In vitro effects of different sources of fibrinogen supplementation on clot initiation and stability in a model of dilutional coagulopathy.
abstract: OBJECTIVE
  To analyse which fibrinogen source may improve coagulation using an in vitro 33% dilutional coagulopathy model.
  
  
  BACKGROUND
  Uncritical volume resuscitation in the context of trauma haemorrhage contributes to the iatrogenic arm of the acute trauma-induced coagulopathy through dilution and depletion of coagulation factors, with fibrinogen reaching critical levels first.
  
  
  METHODS
  By using an experimental model of 33% dilutional coagulopathy, we have analysed which fibrinogen source may exert superior effects on improving haemocoagulative capacities and correcting depleted fibrinogen levels. As fibrinogen sources, we supplemented (i) fresh frozen plasma (FFP), (ii) fibrinogen concentrate low-dose (Fiblow) and (iii) fibrinogen concentrate high-dose (Fibhigh), the latter both in the presence and absence of additional FXIII.
  
  
  RESULTS
  The dilution was associated with decreased haemoglobin and haematocrit levels. Fibrinogen supplementation with fibrinogen-containing formulations led to increased fibrinogen levels (FFP: 172·2 ± 17·4 mg dL-1; Fiblow: 211·5 ± 20·61 mg dL-1; Fibhigh: 255·8 ± 21·4 mg dL-1) than in a diluted-only sample (155·5 ± 19·7 mg dL-1). Extrinsically activated assay with tissue factor (EXTEM) clot formation times, α-angles and maximum clot firmness significantly improved in the groups of Fiblow+ FXIII (79 ± 12·2 s; 74·3 ± 2·4°; 62 ± 2·3 mm), Fibhigh(70·8 ± 10·6 s; 76·2 ± 2·7°; 64·3 ± 2·3 mm) and Fibhigh+ FXIII (69·8 ± 11·5 s; 77·5 ± 2·7°; 64·33 ± 2·5 mm) compared with the dilution groups (104·2 ± 19 s; 69·7 ± 2·9°; 56·5 ± 3·1 mm). In contrast, rotational thromboelastometric trace (ROTEM) measures of samples supplemented with FFP largely remained unchanged.
  
  
  CONCLUSIONS
  Fibrinogen concentrates corrected and improved haemodilution-induced changes in blood clotting in vitro. High-dose fibrinogen supplementation was associated with correction and improvement in clot dynamics and stability.
authors: The Institute for Research in Operative Medicine, Faculty of Health, Department of Medicine, Witten/Herdecke University, Cologne, Germany.
authors: N
authors: N
authors: Schäfer
authors: The Institute for Research in Operative Medicine, Faculty of Health, Department of Medicine, Witten/Herdecke University, Cologne, Germany.|Department of Traumatology, Orthopaedic Surgery and Sports Traumatology, Cologne-Merheim Medical Centre (CMMC), Witten/Herdecke University, Cologne, Germany.|Department of Orthopaedic Surgery, University Hospital RWTH Aachen, Aachen, Germany.
authors: A
authors: A
authors: Driessen
authors: Institute of Transfusion Medicine Cologne-Merheim Medical Centre (CMMC), Witten/Herdecke University, Cologne, Germany.
authors: U
authors: U
authors: Bauerfeind
authors: The Institute for Research in Operative Medicine, Faculty of Health, Department of Medicine, Witten/Herdecke University, Cologne, Germany.|Department of Traumatology, Orthopaedic Surgery and Sports Traumatology, Cologne-Merheim Medical Centre (CMMC), Witten/Herdecke University, Cologne, Germany.
authors: M
authors: M
authors: Fröhlich
authors: The Institute for Research in Operative Medicine, Faculty of Health, Department of Medicine, Witten/Herdecke University, Cologne, Germany.
authors: J
authors: J
authors: Ofir
authors: The Institute for Research in Operative Medicine, Faculty of Health, Department of Medicine, Witten/Herdecke University, Cologne, Germany.
authors: E K
authors: EK
authors: Stürmer
authors: Department of Traumatology, Orthopaedic Surgery and Sports Traumatology, Cologne-Merheim Medical Centre (CMMC), Witten/Herdecke University, Cologne, Germany. Marc.Maegele@t-online.de.
authors: M
authors: M
authors: Maegele
mesh_terms: D000328:Adult; D001779:Blood Coagulation Factors / Q000378:metabolism*; D004211:Disseminated Intravascular Coagulation / Q000097:blood* / Q000188:drug therapy; D005340:Fibrinogen / Q000494:pharmacology*; D006801:Humans; D008297:Male; D008954:Models, Biological; D010949:Plasma; D014947:Wounds and Injuries / Q000097:blood* / Q000188:drug therapy
chemical_list: D001779:Blood Coagulation Factors; D005340:Fibrinogen
keywords: coagulopathy; factor XIII; fibrinogen; fresh frozen plasma; haemocoagulative capacity; haemorrhage; haemostatic potential; trauma-induced coagulopathy