Effect of recombinant FVIIa in hypothermic, coagulopathic pigs with liver injuries.
BACKGROUND
Previous experiments with diverse pig models to evaluate the ability of rFVIIa to reduce hemorrhage have provided divergent results. The current study was conducted to address concerns related to previous work by using larger sample sizes, and an extended observational period of 4 hours post-injury. The objectives were to evaluate further the hemostatic efficacy and safety of rFVIIa administration after traumatic, uncontrolled hemorrhage.


METHODS
Anesthetized, splenectomized pigs (36.6 +/- 0.3 kg; n = 18/group) underwent an approximately 50% isovolemic blood exchange with 33 degrees C 6% hetastarch, and body temperature was adjusted to 32.5 +/- 0.5 degrees C. Subsequently, a Grade V liver injury was inflicted. After 30 seconds, either vehicle or treatment (180 microg/kg or 720 microg/kg rFVIIa) was administered intravenously as a bolus. Concomitantly, laparotomy pads were packed around the liver. Resuscitation with 33 degrees C lactated Ringer's solution (260 mL/min) was initiated and pigs were monitored for 4 hour post-injury or until death. Tissues were collected and examined histologically to assess the presence of disseminated intravascular coagulation (DIC).


RESULTS
Liver injuries were comparable among all groups (p = 0.89). Measures associated with in vitro coagulation (prothrombin time, activated partial thromboplastin time, thromboelastographic split-point and R times) were enhanced by rFVIIa administration (p < 0.05). However, neither percent survival (p = 0.82), survival time (p = 0.56), nor blood loss (p = 0.63) were affected by treatment. DIC was not evident in lung or kidney tissue.


CONCLUSIONS
These data indicate an inability of rFVIIa at these doses to reduce blood loss, or to increase survival time or percent survival in this pig model. Absence of DIC provides evidence for safe use of rFVIIa under conditions specific to this study.
Klemcke
Harold G
HG
U.S. Army Institute of Surgical Research, Fort Sam Houston, TX 78234-6315, USA. harold.klemcke@amedd.army.mil
Delgado
Angel
A
Holcomb
John B
JB
Ryan
Kathy L
KL
Burke
Allen
A
DeGuzman
Rodolpho
R
Scherer
Michael
M
Cortez
Douglas
D
Uscilowicz
John
J
Macaitis
Joseph M
JM
Bliss
Jason
J
Wojtaszczyk
Jennifer
J
Christensen
Suzanne
S
Currier
Heather
H
Pusateri
Anthony E
AE
D000704:Analysis of Variance; D000818:Animals; D001778:Blood Coagulation Disorders / Q000097:blood / Q000150:complications*; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D005167:Factor VII / Q000627:therapeutic use*; D015942:Factor VIIa; D006470:Hemorrhage / Q000517:prevention & control*; D007036:Hypothermia, Induced; D008099:Liver / Q000293:injuries*; D010314:Partial Thromboplastin Time; D011517:Prothrombin Time; D011994:Recombinant Proteins / Q000627:therapeutic use; D016019:Survival Analysis; D013552:Swine
D011994:Recombinant Proteins; D005167:Factor VII; C103587:recombinant FVIIa; D015942:Factor VIIa