Prothrombin complex concentrate versus recombinant factor VIIa for reversal of hemodilutional coagulopathy in a porcine trauma model.
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.
Dickneite
Gerhard
G
Department of Pharmacology and Toxicology, CSL Behring GmbH, Marburg, Germany. gerhard.dickneite@cslbehring.com
Dörr
Bärbel
B
Kaspereit
Franz
F
Tanaka
Kenichi A
KA
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
D001779:Blood Coagulation Factors; D011994:Recombinant Proteins; C025667:prothrombin complex concentrates; C103587:recombinant FVIIa; D015942:Factor VIIa