BJA Advance Access originally published online on May 6, 2009
British Journal of Anaesthesia 2009 102(6):793-799; doi:10.1093/bja/aep098
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Finding the optimal concentration range for fibrinogen replacement after severe haemodilution: an in vitro model
1 Department of Anesthesiology
2 Department of Pathology and Laboratory Medicine, Emory University, School of Medicine, Atlanta, GA, USA
3 Department of Anesthesiology, Hannover Medical School, Hannover, Germany
* Corresponding author: Department of Anesthesiology, Emory University, School of Medicine, 1364 Clifton Road, N.E., Atlanta, GA 30322, USA. E-mail: ktanaka{at}emory.edu
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 µg 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.
Keywords: blood, coagulation; blood, haemodilution; complication, coagulopathy; measurement technique, coagulation
Declaration of interest. Drs N.R.-M., J.H.L., and K.A.T. have served on advisory board meetings on perioperative haemostasis held by CSL Behring.