title: Prothrombin complex concentrate versus recombinant factor VIIa for reversal of hemodilutional coagulopathy in a porcine trauma model.
abstract: BACKGROUND
  Fluid resuscitation after traumatic injury may necessitate coagulation factor replacement to prevent bleeding complications of dilutional coagulopathy. Recombinant activated factor VII (rFVIIa) is being widely investigated as a hemostatic agent in trauma. Multicomponent therapy with prothrombin complex concentrate (PCC) containing coagulation factors II, VII, IX, and X might offer potential advantages.
  
  
  METHODS
  Anesthetized mildly hypothermic normotensive pigs were hemodiluted by substituting 65% to 70% of total blood volume in phases with hydroxyethyl starch and red cells. Thereafter, animals received 12.5 mL . kg isotonic saline placebo, 35 IU . kg PCC, or 180 microg x kg rFVIIa. Immediately afterward, a standardized spleen injury was inflicted, and prothrombin time (PT) and hemostasis were assessed. Thrombin generation was also determined.
  
  
  RESULTS
  Hemodilution depleted levels of factors II, VII, IX, and X markedly, prolonged PT and decreased thrombin formation. PCC and rFVIIa both fully normalized the hemodilution-induced lengthening of PT. In PCC recipients, peak thrombin generation was greater by a median of 60.7 nM (confidence interval 56.4-64.9 nM) compared with the rFVIIa group (p = 0.008). After spleen trauma, time to hemostasis was shortened to a median of 35 minutes in animals treated with PCC versus 94 minutes with rFVIIa (p = 0.016).
  
  
  CONCLUSIONS
  In a pilot study involving an in vivo large-animal model of spleen trauma, PCC accelerated hemostasis and augmented thrombin generation compared with rFVIIa. Further investigations are warranted on PCC as a hemostatic agent in trauma.
authors.affiliation: Department of Pharmacology and Toxicology, CSL Behring GmbH, Marburg, Germany. gerhard.dickneite@cslbehring.com
authors.forename: Gerhard
authors.initials: G
authors.lastname: Dickneite
authors.forename: Bärbel
authors.initials: B
authors.lastname: Dörr
authors.forename: Franz
authors.initials: F
authors.lastname: Kaspereit
authors.forename: Kenichi A
authors.initials: KA
authors.lastname: Tanaka
mesh_terms: D000818:Animals; D001778:Blood Coagulation Disorders / Q000097:blood / Q000188:drug therapy* / Q000209:etiology; D001779:Blood Coagulation Factors / Q000627:therapeutic use*; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D015942:Factor VIIa / Q000627:therapeutic use*; D005440:Fluid Therapy / Q000009:adverse effects / Q000379:methods; D006438:Hemodilution / Q000009:adverse effects* / Q000379:methods; D006470:Hemorrhage / Q000150:complications / Q000628:therapy; D006487:Hemostasis / Q000187:drug effects; D053208:Kaplan-Meier Estimate; D008297:Male; D010865:Pilot Projects; D011517:Prothrombin Time; D011994:Recombinant Proteins / Q000627:therapeutic use; D012151:Resuscitation / Q000009:adverse effects / Q000379:methods; D013154:Spleen / Q000293:injuries; D018709:Statistics, Nonparametric; D013552:Swine; D013997:Time Factors; D016896:Treatment Outcome; D014947:Wounds and Injuries / Q000150:complications* / Q000628:therapy
chemical_list: D001779:Blood Coagulation Factors; D011994:Recombinant Proteins; C025667:prothrombin complex concentrates; C103587:recombinant FVIIa; D015942:Factor VIIa