Early Injection of High-Dose Recombinant Factor VIIa Decreases Blood Loss and Prolongs Time from Injury to Death in Experimental Liver Injury

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Abstract
Recombinant factor VIIa (rFVIIa) is used for treatment of bleeding episodes in hemophilia patients who develop inhibitors to factors VIII and IX. We tested the hypothesis that administration of rFVIIa early after injury would decrease bleeding and prolong the time from injury to death after experimental hepatic trauma. Anesthetized swine were cannulated for blood sampling and hemodynamic monitoring. Avulsion of the left median lobe of the liver induced uncontrolled hemorrhage. After a 10% reduction in mean arterial pressure, animals (n = 8 per group) were blindly randomized to receive intravenous rFVIIa 180 microg/kg, rFVIIa 720 microg/kg, or placebo. Pathologic examination of brain, lung, kidney, heart, and small bowel was performed to assess intravascular thrombosis. RESULTS Mortality during the first hour was 50% (four of eight) in controls versus 0% with rFVIIa 720 microg/kg (p = 0.02, chi2). Blood loss was decreased in the rFVIIa 720 microg/kg group versus the placebo group (13.2 +/- 5.5 mL/kg vs. 21.9 +/- 7.7 mL/kg;p = 0.0223). Time from injury to death was significantly prolonged in the rFVIIa 720 microg/kg group compared with placebo (116 minutes vs. 8.5 +/- 3.5 minutes; p= 0.02). No macro- or microthrombi in vital organs were identified on pathologic examination. Intravenous administration of high-dose rFVIIa early after induction of hemorrhage decreased bleeding and prolonged survival. No evidence of thrombosis in vital organs was observed.