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BJA Advance Access published online on January 24, 2009
British Journal of Anaesthesia, doi:10.1093/bja/aen391
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© 2009 The Author(s)
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.0/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Prothrombin complex concentrate vs fresh frozen plasma for reversal of dilutional coagulopathy in a porcine trauma model

G. Dickneite{dagger},* and I. Pragst{dagger}

Department of Pharmacology and Toxicology, CSL Behring GmbH, Marburg, Germany

* Corresponding author. E-mail: gerhard.dickneite{at}cslbehring.com

Background: Fluid resuscitation following traumatic injury causes haemodilution and can contribute to coagulopathy. Coagulation factor replacement may be necessary to prevent bleeding complications of dilutional coagulopathy. Compared with fresh frozen plasma (FFP), prothrombin complex concentrate (PCC) may potentially offer a more rapid and effective means of normalizing coagulation factor levels.

Methods: In anaesthetized mildly hypothermic pigs, 65–70% of total blood volume was substituted in phases with hydroxyethyl starch and red cells. Animals were then treated with 15 ml kg–1 isotonic saline placebo, 25 IU kg–1 PCC, or 15 ml kg–1 FFP. Immediately thereafter, either a standardized femur or spleen injury was inflicted, and coagulation function, including thrombin generation, and bleeding were assessed. An additional group received high-dose FFP (40 ml kg–1) before femur injury.

Results: Haemodilution markedly prolonged prothrombin time and reduced peak thrombin generation. PCC, but not FFP, fully reversed those effects. Compared with 15 ml kg–1 FFP, PCC shortened the time to haemostasis after either bone (P=0.001) or spleen (P=0.028) trauma and reduced the volume of blood lost (P<0.001 and P=0.015, respectively). Subsequent to bone injury, PCC also accelerated haemostasis (P=0.003) and diminished blood loss (P=0.006) vs 40 ml kg–1 FFP.

Conclusions: PCC was effective in correcting dilutional coagulopathy and controlling bleeding in an in vivo large-animal trauma model. In light of its suitability for more rapid administration than FFP, PCC merits further investigation as a therapy for dilutional coagulopathy in trauma and surgery.

Keywords: blood, haemodilution; complications, haemorrhagic disorder; complications, trauma; fresh frozen plasma; prothrombin complex concentrate

{dagger} Declaration of interest. Gerhard Dickneite and Ingo Pragst are employees of CSL Behring.


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