Intravenous rFVIIa administered for hemorrhage control in hypothermic coagulopathic swine with grade V liver injuries

Uri Martinowitz, John B. Holcomb*, Anthony E. Pusateri, Michael Stein, Nicholas Onaca, Mony Freidman, Joseph M. Macaitis, D. Castel, Ulla Hedner, John R. Hess

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

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°C core temperature. The swine then received a grade V liver injury and 30 seconds later, either 180 μg/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 howel were obtained to evaluate for the presence of microvascular thrombi. Results: At the time of injury, core temperature was 33.3° ± 0.4°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 × 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. Conclusion: 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.

Original languageEnglish
Pages (from-to)721-729
Number of pages9
JournalJournal of Trauma
Volume50
Issue number4
DOIs
StatePublished - 2001
Externally publishedYes

Keywords

  • Animals
  • Coagulation factor VII
  • Coagulopathy
  • Hemorrhage
  • Hypothermia
  • Injury
  • Liver
  • rFVIIa

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