Intravenous rFVIIa administered for hemorrhage control in hypothermic coagulopathic swine with grade V liver injuries.
BACKGROUND
Intravenous administration of recombinant activated human clotting factor VII (rFVIIa) has been used successfully to prevent bleeding in hemophilia patients undergoing elective surgery, but not in previously normal trauma patients. This study was conducted to determine whether rFVIIa was a useful adjunct to gauze packing for decreasing blood loss from grade V liver injuries in hypothermic and coagulopathic swine.


METHODS
All animals (n = 10, 35 +/- 2 kg) underwent a 60% isovolemic exchange transfusion with 6% hydroxyethyl starch and were cooled to 33 degrees C core temperature. The swine then received a grade V liver injury and 30 seconds later, either 180 microg/kg rFVIIa, or saline control. All animals were gauze packed 30 seconds after injury and resuscitated 5.5 minutes after injury with lactated Ringer's solution to their preinjury mean arterial pressure. Posttreatment blood loss, mean arterial pressure, resuscitation volume, and clotting studies were monitored for 1 hour. Histology of lung, kidney, and small bowel were obtained to evaluate for the presence of microvascular thrombi.


RESULTS
At the time of injury, core temperature was 33.3 degrees +/- 0.4 degrees C, hemoglobin was 6 +/- 0.7 g/dL, prothrombin time was 19.1 +/- 1.0 seconds, activated partial thromboplastin time was 29.0 +/- 4.8 seconds, fibrinogen was 91 +/- 20 mg/dL, and platelets were 221 +/- 57 x 105/mL, with no differences between groups (p > 0.05). Clotting factor levels confirmed a coagulopathy at the preinjury point. The posttreatment blood loss was less (p < 0.05) in group 1 (527 +/- 323 mL), than in group 2 (976 +/- 573 mL). The resuscitation volume was not different (p > 0.05). One-hour survival in both groups was 100%. Compared with the control group, rFVIIa increased the circulating levels of VIIa and, despite hypothermia, shortened the prothrombin time 5 minutes after injection (p < 0.05). Laboratory evaluation revealed no systemic activation of the clotting cascade. Postmortem evaluation revealed no evidence of large clots in the hepatic veins or inferior vena cava, or microscopic thrombi in lung, kidney, or small intestine.


CONCLUSIONS
rFVIIa reduced blood loss and restored abnormal coagulation function when used in conjunction with liver packing in hypothermic and coagulopathic swine. No adverse effects were identified.
Martinowitz
U
U
Michael E. DeBakey Department of Surgery, Baylor College of Medicine, Joint Trauma Training Center, Ben Taub General Hospital, Houston, Texas 77030, USA.
Holcomb
J B
JB
Pusateri
A E
AE
Stein
M
M
Onaca
N
N
Freidman
M
M
Macaitis
J M
JM
Castel
D
D
Hedner
U
U
Hess
J R
JR
D000818:Animals; D001458:Bandages; D001778:Blood Coagulation Disorders / Q000097:blood / Q000150:complications*; D001794:Blood Pressure; D003131:Combined Modality Therapy; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D005078:Exchange Transfusion, Whole Blood; D005167:Factor VII / Q000009:adverse effects / Q000627:therapeutic use*; D015942:Factor VIIa; D005340:Fibrinogen / Q000378:metabolism; D006470:Hemorrhage / Q000097:blood / Q000188:drug therapy* / Q000209:etiology*; D007036:Hypothermia, Induced / Q000379:methods*; D007552:Isotonic Solutions / Q000627:therapeutic use; D008099:Liver / Q000293:injuries*; D010314:Partial Thromboplastin Time; D011517:Prothrombin Time; D011897:Random Allocation; D011994:Recombinant Proteins / Q000009:adverse effects / Q000627:therapeutic use*; D012151:Resuscitation / Q000379:methods; D000077325:Ringer's Lactate; D016037:Single-Blind Method; D016019:Survival Analysis; D013552:Swine; D013927:Thrombosis / Q000209:etiology / Q000473:pathology; D013997:Time Factors; D014947:Wounds and Injuries / Q000145:classification / Q000150:complications / Q000401:mortality
D007552:Isotonic Solutions; D011994:Recombinant Proteins; D000077325:Ringer's Lactate; D005167:Factor VII; D005340:Fibrinogen; C103587:recombinant FVIIa; D015942:Factor VIIa