title: Thrombelastographic whole blood clot formation after ex vivo addition of plasma substitutes: improvements of the induced coagulopathy with fibrinogen concentrate.
abstract: BACKGROUND
  Plasma substitutes such as hydroxyethyl starch (HES) and various dextrans may compromise the haemostatic system, thereby causing potentially dangerous bleeding. Whilst several mechanisms have been advanced to explain the nature of the coagulopathy induced by this colloid, there has been comparably little interest in devising ways to optimize haemostasis after a relative colloid overdose.
  
  
  METHODS
  Real-time whole blood (WB) clot formation profiles were recorded using a thrombelastographic method employing activation with tissue factor. The coagulation tracings were transformed into dynamic velocity profiles of WB clot formation. WB from healthy individuals (n=20) was exposed to haemodilution of approximately 55% with isotonic saline, HES 200/0.5, HES 130/0.4, and dextran 70, respectively. Possible modalities for improvement of the induced coagulopathy were explored, in particular ex vivo addition of a fibrinogen concentrate.
  
  
  RESULTS
  WB coagulation profiles changed significantly with decreased clot strength, and a compromised propagation phase of clot formation. The duration of the initiation phase of WB coagulation was unchanged. No statistical differences were detected amongst the HES solutions and dextran 70. However, dextran 70 returned a more suppressed clot development and strength compared with the HES solutions. Ex vivo haemostatic addition of washed platelets (75 x 10(9) litre(-1)) and factor VIII (0.6 IU ml(-1)) produced insignificant changes in clot initiation, propagation, and in the clot strength. In contrast, ex vivo addition of a fibrinogen concentrate (1 g litre(-1)) improved the coagulopathy induced by all of the three individual plasma expanders tested.
  
  
  CONCLUSIONS
  Coagulopathy induced by haemodilution with either HES 200/0.5, HES 130/0.4, and dextran 70 may be improved by fibrinogen supplementation.
authors.affiliation: Department of Anaesthesiology, Aarhus University Hospital, Aarhus Sygehus, Denmark.
authors.forename: C
authors.initials: C
authors.lastname: Fenger-Eriksen
authors.forename: E
authors.initials: E
authors.lastname: Anker-Møller
authors.forename: J
authors.initials: J
authors.lastname: Heslop
authors.forename: J
authors.initials: J
authors.lastname: Ingerslev
authors.forename: B
authors.initials: B
authors.lastname: Sørensen
mesh_terms: D000328:Adult; D001778:Blood Coagulation Disorders / Q000188:drug therapy* / Q000209:etiology*; D001800:Blood Specimen Collection / Q000379:methods; D003911:Dextrans / Q000009:adverse effects; D005260:Female; D005340:Fibrinogen / Q000627:therapeutic use*; D006438:Hemodilution / Q000009:adverse effects*; D006489:Hemostatic Techniques; D006801:Humans; D006895:Hydroxyethyl Starch Derivatives / Q000009:adverse effects; D066298:In Vitro Techniques; D007552:Isotonic Solutions; D008297:Male; D008875:Middle Aged; D010952:Plasma Substitutes / Q000009:adverse effects*; D012965:Sodium Chloride / Q000009:adverse effects; D013916:Thrombelastography / Q000379:methods
chemical_list: D003911:Dextrans; D006895:Hydroxyethyl Starch Derivatives; D007552:Isotonic Solutions; D010952:Plasma Substitutes; D012965:Sodium Chloride; D005340:Fibrinogen