The effect of recombinant factor VIIa on coagulopathic pigs with grade V liver injuries.
BACKGROUND
Recombinant factor VIIa (rFVIIa) has been used to decrease bleeding in a number of settings including hemophilia, liver transplantation, intractable bleeding, and cirrhosis. Experience in the trauma setting is limited. This study was performed to determine whether rFVIIa would reduce bleeding after a grade V liver injury in hypothermic, dilutionally coagulopathic pigs when used as an adjunct to abdominal packing and to determine whether increasing the dose of the drug increased its hemostatic efficacy.


METHODS
Thirty animals were randomized to receive 180 microg/kg of rFVIIa, 720 microg/kg of rFVIIa, or vehicle buffer control. After laparotomy and splenectomy, animals underwent a 60% blood volume isovolemic exchange transfusion with 5% human albumin. The animals' temperature was maintained at 33 degrees C and a standardized grade V liver injury was made with a liver clamp. Thirty seconds after injury, the abdomen was packed with laparotomy sponges, resuscitation was initiated, and blinded therapy was given. Animals were resuscitated to their baseline mean arterial pressure and the study was continued for 2 hours. Serial coagulation parameters were measured at the temperature they were drawn. After the study period, surviving animals were killed, posttreatment blood loss was measured, and an autopsy was performed.


RESULTS
Ten animals were randomized to each group. After administration of study drug, factor VII clotting activity (FVII:C) was higher in the 720 microg/kg group than in the 180 microg/kg group (p < 0.01). FVII:C was higher in both treatment groups than in the control group (p < 0.01). The mean prothrombin time was shorter in the treatment groups than in the control group (p < 0.05). Mean arterial pressure was lower in the control group than in the treatment groups throughout the study (p < 0.01). Mean blood loss was less in the treatment groups than in the control group (p = 0.03). Mortality was not different between groups. There were no differences between the groups that received rFVIIa in any measured parameters except for FVII:C. Liver injuries were similar between groups and there was no evidence of microthrombosis on lung histology.


CONCLUSIONS
rFVIIa reduces blood loss in hypothermic, dilutionally coagulopathic pigs with grade V injuries when used as an adjunct to packing. Increasing the dose does not enhance the hemostatic effect.
Schreiber
Martin A
MA
Michael E. DeBakey Department of Surgery, Baylor College of Medicine, University of Texas at Houston, Houston, Texas, USA. schreibm@ohsu.edu
Holcomb
John B
JB
Hedner
Ulla
U
Brundage
Susan I
SI
Macaitis
Joseph M
JM
Hoots
Keith
K
D000818:Animals; D001778:Blood Coagulation Disorders / Q000188:drug therapy* / Q000209:etiology; D001780:Blood Coagulation Tests; D015942:Factor VIIa / Q000627:therapeutic use*; D005260:Female; D006470:Hemorrhage / Q000188:drug therapy* / Q000209:etiology; D006490:Hemostatics / Q000627:therapeutic use*; D007035:Hypothermia / Q000209:etiology; D008099:Liver / Q000293:injuries*; D008297:Male; D011897:Random Allocation; D011994:Recombinant Proteins; D012771:Shock, Hemorrhagic / Q000188:drug therapy / Q000209:etiology; D013552:Swine
D006490:Hemostatics; D011994:Recombinant Proteins; D015942:Factor VIIa