Effects of different fibrinogen concentrations on blood loss and coagulation parameters in a pig model of coagulopathy with blunt liver injury.
BACKGROUND
The early application of fibrinogen could potentially reverse haemodilution-induced coagulopathy, although the impact of varying concentrations of fibrinogen to reverse dilutional coagulopathy has not been studied in vivo. We postulated that fibrinogen concentration is correlated with blood loss in a pig model of coagulopathy with blunt liver injury.


METHODS
Coagulopathy was induced in 18 anaesthetized pigs (32 +/- 1.6 kg body weight) by replacing 80% of blood volume with hydroxyethylstarch 130/0.4 and Ringer's lactated solution, and re-transfusion of erythrocytes. Animals were randomly assigned to receive either 70 mg kg-1 (F-70) or 200 mg kg-1 (F-200) fibrinogen or placebo before inducing blunt liver injury using a force of 225 +/- 26 Newton. Haemodynamics, coagulation parameters and blood loss were monitored for 2 hours. After death, histological examination of internal organs was performed to assess the presence of emboli and the equality of liver injury.


RESULTS
Plasma dilution caused severe coagulopathy. Measured by thromboelastography fibrinogen restored coagulation dose-dependently. Total blood loss was significantly lower and survival better in both fibrinogen groups as compared to controls (P < 0.05). Between the F-70 (1317 +/- 113 ml) and the F-200 group (1155 +/- 232 ml) no significant difference in total blood loss could be observed, despite improved coagulation parameters in the F-200 group (P < 0.05). Microscopy revealed even injury pattern and no (micro) thrombi for either group.


CONCLUSIONS
Restoring fibrinogen with 70 or 200 mg kg-1 after severe dilutional coagulopathy safely improved coagulation and attenuated blood loss after experimental blunt liver trauma. The higher dosage of fibrinogen was not associated with a further reduction in blood loss.
Grottke
Oliver
O
Department of Anaesthesiology, RWTH Aachen University Hospital Pauwelsstrasse 30, Aachen, Germany. ogrottke@ukaachen.de
Braunschweig
Till
T
Henzler
Dietrich
D
Coburn
Mark
M
Tolba
Rene
R
Rossaint
Rolf
R
D000818:Animals; D001777:Blood Coagulation / Q000187:drug effects; D001778:Blood Coagulation Disorders / Q000139:chemically induced* / Q000188:drug therapy / Q000503:physiopathology; D005340:Fibrinogen / Q000008:administration & dosage / Q000378:metabolism / Q000627:therapeutic use*; D006438:Hemodilution; D006470:Hemorrhage / Q000188:drug therapy*; D008099:Liver / Q000098:blood supply / Q000293:injuries*; D023421:Models, Animal; D011897:Random Allocation; D013552:Swine; D014949:Wounds, Nonpenetrating / Q000097:blood* / Q000503:physiopathology
D005340:Fibrinogen
Anesth Analg. 2009 Mar;108(3):751-8
19224779
Thromb Haemost. 2009 Jul;102(1):137-44
19572078
J Thromb Haemost. 2007 May;5(5):1019-25
17461931
Br J Anaesth. 2009 Jun;102(6):793-9
19420005
J Trauma. 1995 Mar;38(3):323-4
7897707
Anesth Analg. 2007 Oct;105(4):905-17, table of contents
17898365
Anesth Analg. 1995 Aug;81(2):360-5
7542432
Br J Haematol. 2004 Jul;126(1):11-28
15198728
J Thromb Haemost. 2009 May;7(5):795-802
19320829
J Thromb Haemost. 2007 Feb;5(2):266-73
17087729
Br J Anaesth. 2005 Aug;95(2):172-7
15923269
Eur Surg Res. 2010;44(2):65-73
19996600
Thromb Haemost. 2008 Jan;99(1):64-70
18217136
Acta Anaesthesiol Scand. 2005 Feb;49(2):222-31
15715625
Anesth Analg. 2008 May;106(5):1360-5, table of contents
18420845
Anesth Analg. 2006 Feb;102(2):347-51
16428520
J Thromb Haemost. 2004 Jan;2(1):147-53
14717978
Am J Physiol. 1955 Apr;181(1):9-14
14376559
J Trauma. 2008 Oct;65(4):748-54
18849786
Crit Care. 2007;11(1):R17
17298665
Thromb Res. 2001 Dec 15;104(6):467-74
11755957
Blood Coagul Fibrinolysis. 2009 Oct;20(7):535-40
19710609
Blood. 1996 Aug 1;88(3):907-14
8704248
Cochrane Database Syst Rev. 2010 Jan 20;(1):CD007594
20091640
Br J Anaesth. 2005 Mar;94(3):324-9
15608046
Transfus Med Rev. 2009 Jul;23(3):177-88
19539873
J Trauma. 2007 Jun;62(6):1352-9; discussion 1359-61
17563647
Haemophilia. 2006 Dec;12 Suppl 6:48-52; discussion 52-3
17123394
Blood Coagul Fibrinolysis. 1995 Dec;6(8):743-6
8825225
Cardiol J. 2009;16(4):317-20
19653173
Arterioscler Thromb Vasc Biol. 2005 Dec;25(12):2463-9
16179597
Transfusion. 2008 Nov;48(11):2384-94
18673348
Thromb Res. 2006;117(5):597-602
15985284
Thromb Haemost. 1995 Jul;74(1):460-3
8578507
Br J Anaesth. 2009 Jun;102(6):785-92
19411671
Anesth Analg. 2004 Jul;99(1):120-123
15281516
Thromb Haemost. 1997 Jul;78(1):611-6
9198225
Ann Thorac Surg. 2007 May;83(5 Suppl):S27-86
17462454