Prothrombin complex concentrate (Beriplex P/N) for control of bleeding after kidney trauma in a rabbit dilutional coagulopathy model.
BACKGROUND
Fluid resuscitation after trauma often results in dilutional coagulopathy that may hinder control of bleeding and, once initial hemostasis has been secured, heighten risk of perioperative bleeding when further surgery is required. Since multiple coagulation factor deficiencies typically accompany fluid resuscitation, prothrombin complex concentrate (PCC) containing factors II, VII, IX and X may potentially offer greater hemostatic efficacy than coagulation factor monotherapy.


METHODS
Anesthetized normothermic rabbits were hemodiluted 50-60% by phased blood withdrawal and infusion of hydroxyethyl starch and erythrocytes. The animals were randomly assigned to receive saline placebo, 25 IU x kg(-1) PCC (Beriplex P/N) or 180 microg x kg(-1) activated recombinant factor VII (rFVIIa; NovoSeven). Immediately thereafter, bleeding was precipitated by a standardized kidney incision.


RESULTS
PCC accelerated hemostasis compared both with saline and rFVIIa (p=0.002 for both comparisons). The median times to hemostasis in the PCC, saline and rFVIIa groups were 12, 19 and 28 min, respectively. PCC reduced blood loss by a median of 43 mL with a 95% confidence interval (CI) of 8.0-67.5 mL vs. saline and 82 mL (CI, 35.0-110.0 mL) vs. rFVIIa. PCC augmented peak thrombin generation by a median of 104.1 nM (CI, 78.3-142.3 nM) compared with saline and 105.8 nM (CI, 70.7-139.5 nM ) relative to rFVIIa. At the respective 180 microg x kg(-1) and 25 IU x kg(-1) doses tested, rFVIIa displayed thrombogenicity in the Wessler stasis model, while PCC did not.


CONCLUSIONS
In an animal model of dilutional coagulopathy and kidney trauma, PCC accelerated hemostasis and diminished blood loss compared with rFVIIa monotherapy.
Pragst
Ingo
I
Department of Pharmacology and Toxicology, CSL Behring GmbH, Marburg, Germany.
Kaspereit
Franz
F
Dörr
Bärbel
B
Dickneite
Gerhard
G
D000818:Animals; D001778:Blood Coagulation Disorders / Q000209:etiology / Q000628:therapy*; D001779:Blood Coagulation Factors / Q000627:therapeutic use*; D004195:Disease Models, Animal; D005260:Female; D006438:Hemodilution / Q000379:methods; D006470:Hemorrhage / Q000209:etiology / Q000628:therapy*; D006487:Hemostasis; D007668:Kidney / Q000293:injuries*; D011517:Prothrombin Time; D011817:Rabbits; D011897:Random Allocation; D014947:Wounds and Injuries / Q000628:therapy*
D001779:Blood Coagulation Factors; C025667:prothrombin complex concentrates