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Finding the optimal concentration range for fibrinogen replacement after severe haemodilution: an in vitro model.

Publication ,  Journal Article
Bolliger, D; Szlam, F; Molinaro, RJ; Rahe-Meyer, N; Levy, JH; Tanaka, KA
Published in: Br J Anaesth
June 2009

BACKGROUND: Replacement of fibrinogen is presumably the key step in managing dilutional coagulopathy. We performed an in vitro study hypothesizing that there is a minimal fibrinogen concentration in diluted whole blood above which the rate of clot formation approaches normal. METHODS: Blood samples from six healthy volunteers were diluted 1:5 v/v with saline keeping haematocrit at 24% using red cell concentrates. We measured coagulation factors and thrombin generation in plasma at baseline and after dilution. Thromboelastometry was used to evaluate (i) speed and quality of clot formation in diluted samples supplemented with fibrinogen 50-300 mg dl(-1) and (ii) clot resistance to fibrinolysis. Diluted and undiluted samples with no added fibrinogen served as controls. RESULTS: Coagulation parameters and platelets were reduced by 74-85% after dilution. Peak thrombin generation was reduced by 56%. Adding fibrinogen led to a concentration-dependent improvement of all thromboelastometric parameters. The half maximal effective concentration (EC50) for fibrinogen replacement in haemodiluted blood was calculated to be 125 mg dl(-1). Adding tissue plasminogen activator, 0.15 microg ml(-1), led to a decrease of clot firmness and lysis time. CONCLUSIONS: The target plasma concentration for fibrinogen replacement was predicted by these in vitro results to be greater than 200 mg dl(-1) as only these concentrations optimized the rate of clot formation. This concentration is twice the level suggested by the current transfusion guidelines. Although improved, clots were prone to fibrinolysis indicating that the efficacy of fibrinogen therapy may be influenced by co-existing fibrinolytic tendency occurring during dilutional coagulopathy.

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Published In

Br J Anaesth

DOI

EISSN

1471-6771

Publication Date

June 2009

Volume

102

Issue

6

Start / End Page

793 / 799

Location

England

Related Subject Headings

  • Tissue Plasminogen Activator
  • Thrombin
  • Thrombelastography
  • Platelet Count
  • In Vitro Techniques
  • Humans
  • Hemodilution
  • Hematocrit
  • Fibrinolysis
  • Fibrinogen
 

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Bolliger, D., Szlam, F., Molinaro, R. J., Rahe-Meyer, N., Levy, J. H., & Tanaka, K. A. (2009). Finding the optimal concentration range for fibrinogen replacement after severe haemodilution: an in vitro model. Br J Anaesth, 102(6), 793–799. https://doi.org/10.1093/bja/aep098
Bolliger, D., F. Szlam, R. J. Molinaro, N. Rahe-Meyer, J. H. Levy, and K. A. Tanaka. “Finding the optimal concentration range for fibrinogen replacement after severe haemodilution: an in vitro model.Br J Anaesth 102, no. 6 (June 2009): 793–99. https://doi.org/10.1093/bja/aep098.
Bolliger D, Szlam F, Molinaro RJ, Rahe-Meyer N, Levy JH, Tanaka KA. Finding the optimal concentration range for fibrinogen replacement after severe haemodilution: an in vitro model. Br J Anaesth. 2009 Jun;102(6):793–9.
Bolliger, D., et al. “Finding the optimal concentration range for fibrinogen replacement after severe haemodilution: an in vitro model.Br J Anaesth, vol. 102, no. 6, June 2009, pp. 793–99. Pubmed, doi:10.1093/bja/aep098.
Bolliger D, Szlam F, Molinaro RJ, Rahe-Meyer N, Levy JH, Tanaka KA. Finding the optimal concentration range for fibrinogen replacement after severe haemodilution: an in vitro model. Br J Anaesth. 2009 Jun;102(6):793–799.
Journal cover image

Published In

Br J Anaesth

DOI

EISSN

1471-6771

Publication Date

June 2009

Volume

102

Issue

6

Start / End Page

793 / 799

Location

England

Related Subject Headings

  • Tissue Plasminogen Activator
  • Thrombin
  • Thrombelastography
  • Platelet Count
  • In Vitro Techniques
  • Humans
  • Hemodilution
  • Hematocrit
  • Fibrinolysis
  • Fibrinogen