title: The in vitro effects of fibrinogen concentrate, factor XIII and fresh frozen plasma on impaired clot formation after 60% dilution.
abstract: BACKGROUND
  Previous investigations have shown that increasing fibrinogen concentration improves dilution-dependent impairment of clot formation. We conducted an in vitro study to explore whether substitution with fibrin-stabilizing factor XIII (FXIII) combined with fibrinogen promotes further improvement of clot formation, and whether fibrinogen administration as concentrate or fresh frozen plasma (FFP) results in comparable effects.
  
  
  METHODS
  Blood from six healthy donors was diluted by 60% using lactated Ringer's solution. Aliquots of diluted blood samples were incubated with two different doses of fibrinogen concentrate, FXIII concentrate, the combination of both, or with two different doses of FFP. Using thrombelastometry (ROTEM) blood samples were analyzed at baseline (undiluted), after dilution and after supplementation. Variables were analyzed for changes from baseline, and effects of fibrinogen concentrate alone or combined with FXIII were compared with effects observed with corresponding FFP doses.
  
  
  RESULTS
  After 60% in vitro dilution of blood all ROTEM parameters and global coagulation tests changed significantly. Among the substitutes tested FXIII alone had no effect, the combination with fibrinogen improved coagulation time, alpha angle and fibrinogen/fibrin polymerization significantly more than did small-dose fibrinogen alone. After substituting fibrinogen, median values of all ROTEM variables were within the normal range, thereby showing dose dependency but also significant differences (P = 0.027) from corresponding FFP doses (EXTEM MCF FFP small dose [38 (35, 40.3) mm)], which enabled only coagulation time to be shortened to baseline levels.
  
  
  CONCLUSIONS
  Supplementation of fibrinogen restored all ROTEM parameters after dilution. This effect was partially enhanced by adding FXIII and was significantly stronger than for FFP substitution.
authors.affiliation: Department of Anaesthesiology and Critical Care Medicine, Innsbruck Medical University, Anichstrasse 35, 6020 Innsbruck, Austria. thorsten.haas@i-med.ac.at
authors.forename: Thorsten
authors.initials: T
authors.lastname: Haas
authors.forename: Dietmar
authors.initials: D
authors.lastname: Fries
authors.forename: Corinna
authors.initials: C
authors.lastname: Velik-Salchner
authors.forename: Christian
authors.initials: C
authors.lastname: Reif
authors.forename: Anton
authors.initials: A
authors.lastname: Klingler
authors.forename: Petra
authors.initials: P
authors.lastname: Innerhofer
mesh_terms: D001777:Blood Coagulation / Q000187:drug effects*; D001778:Blood Coagulation Disorders / Q000097:blood / Q000188:drug therapy* / Q000209:etiology; D003029:Coagulants / Q000494:pharmacology* / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D005176:Factor XIII / Q000494:pharmacology* / Q000627:therapeutic use; D005340:Fibrinogen / Q000378:metabolism / Q000494:pharmacology* / Q000627:therapeutic use; D006400:Hematocrit; D006438:Hemodilution / Q000009:adverse effects*; D006801:Humans; D007700:Kinetics; D010314:Partial Thromboplastin Time; D010976:Platelet Count; D011517:Prothrombin Time; D013916:Thrombelastography
chemical_list: D003029:Coagulants; D005340:Fibrinogen; D005176:Factor XIII