title: Role of fibrinogen-, factor VIII- and XIII-mediated clot propagation in gelatin haemodilution.
abstract: BACKGROUND
  Gelatin solution impairs coagulation. The mechanism of coagulopathy is incompletely defined. The purpose of this study was to evaluate the capacity of single coagulation factors to reverse gelatin-promoted whole-blood coagulation disorders in vitro.
  
  
  METHODS
  Venous blood was withdrawn from 12 volunteers in a crossover study. Four percent succinylated gelatin was added to citrated whole-blood samples to make a 40 vol% end-concentration of gelatin. The baseline and 40 vol% samples, and samples with addition of fresh-frozen plasma (FFP), fibrinogen, coagulation factors XIII (FXIII) or VIII, together with the von Willebrand factor (FVIII+vWF), were analysed by thromboelastometry (ROTEM. Coagulation was initiated by tissue thromboplastin (ExTEM with and without cytochalasin to determine the functional component of fibrinogen (FibTEM.
  
  
  RESULTS
  Initiation of coagulation and fibrin formation were delayed at 40 vol% gelatin dilution. At this stage, the median (25th-75th percentiles) maximum clot firmness (MCF) was 76.3 (65.9-80.0) and 32.5 (27.4-45.0)% of the pre-dilution value in ExTEM and FibTEM thromboelastometry, respectively. Coagulation time was corrected by addition of fibrinogen and FFP in ExTEM and FibTEM analysis, whereas FVIII or FXIII had minimal effects. MCF was partly restored only by FFP in ExTEM. In FibTEM analysis, MCF improved more by fibrinogen than by FVIII+VWF, FXIII or FFP.
  
  
  CONCLUSIONS
  Gelatin-induced whole-blood coagulation disorder in vitro is mainly dependent on the initial fibrinogen-fibrin interaction. The proposed mechanism might suggest not to reverse gelatin coagulopathy solely by fibrinogen administration. The administration of FFP, a mixture of different coagulation factors, reversed the gelatin-induced in vitro coagulopathy the best.
authors.affiliation: Department of Anaesthesiology and Intensive Care Medicine, Helsinki University Central Hospital, Helsinki, Finland. alexey.schramko@hus.fi
authors.forename: A A
authors.initials: AA
authors.lastname: Schramko
authors.forename: A H
authors.initials: AH
authors.lastname: Kuitunen
authors.forename: R T
authors.initials: RT
authors.lastname: Suojaranta-Ylinen
authors.forename: T T
authors.initials: TT
authors.lastname: Niemi
mesh_terms: D000328:Adult; D001777:Blood Coagulation / Q000187:drug effects* / Q000502:physiology*; D018592:Cross-Over Studies; D005169:Factor VIII / Q000502:physiology*; D005176:Factor XIII / Q000502:physiology*; D005260:Female; D005337:Fibrin / Q000378:metabolism; D005340:Fibrinogen / Q000502:physiology*; D005780:Gelatin / Q000494:pharmacology*; D006400:Hematocrit; D006438:Hemodilution; D006801:Humans; D008297:Male; D010976:Platelet Count; D055815:Young Adult
chemical_list: D005780:Gelatin; D005169:Factor VIII; D005337:Fibrin; D005340:Fibrinogen; D005176:Factor XIII