Prothrombin complex concentrate vs fresh frozen plasma for reversal of dilutional coagulopathy in a porcine trauma model.
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.
Dickneite
G
G
Department of Pharmacology and Toxicology, CSL Behring GmbH, Marburg, Germany. gerhard.dickneite@cslbehring.com
Pragst
I
I
D000818:Animals; D001778:Blood Coagulation Disorders / Q000209:etiology / Q000628:therapy*; D001779:Blood Coagulation Factors / Q000378:metabolism / Q000627:therapeutic use*; D004195:Disease Models, Animal; D006438:Hemodilution / Q000009:adverse effects*; D006470:Hemorrhage / Q000097:blood / Q000209:etiology / Q000628:therapy; D006487:Hemostasis; D008297:Male; D010949:Plasma; D010976:Platelet Count; D011517:Prothrombin Time; D034421:Sus scrofa; D013917:Thrombin / Q000096:biosynthesis; D014947:Wounds and Injuries / Q000097:blood / Q000150:complications / Q000628:therapy*
D001779:Blood Coagulation Factors; C025667:prothrombin complex concentrates; D013917:Thrombin