Early injection of high-dose recombinant factor VIIa decreases blood loss and prolongs time from injury to death in experimental liver injury

Igor Jeroukhimov, Dory Jewelewicz, Julia Zaias, George Hensley, Jana MacLeod, Stephen M. Cohn, Qammar Rashid, Francisco Pernas, Marlies R. Ledford, Eleanor Gomez-Fein, Mauricio Lynn

Research output: Contribution to journalArticle

57 Citations (Scopus)

Abstract

Background: 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. Methods: 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 μg/kg, rFVIIa 720 μg/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 μg/kg (p = 0.02, χ2). Blood loss was decreased in the rFVIIa 720 μg/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 μg/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. Conclusion: 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.

Original languageEnglish (US)
Pages (from-to)1053-1057
Number of pages5
JournalJournal of Trauma - Injury, Infection and Critical Care
Volume53
Issue number6
StatePublished - Dec 1 2002
Externally publishedYes

Fingerprint

Injections
Liver
Wounds and Injuries
Hemorrhage
Placebos
Thrombosis
Factor IX
Bleeding Time
recombinant FVIIa
Factor VIII
Hemophilia A
Intravenous Administration
Arterial Pressure
Swine
Hemodynamics
Kidney
Lung
Survival
Mortality
Brain

Keywords

  • Hemorrhage
  • Hepatic trauma
  • Liver injury
  • Recombinant factor VIIa
  • Shock
  • Thrombosis

ASJC Scopus subject areas

  • Surgery

Cite this

Early injection of high-dose recombinant factor VIIa decreases blood loss and prolongs time from injury to death in experimental liver injury. / Jeroukhimov, Igor; Jewelewicz, Dory; Zaias, Julia; Hensley, George; MacLeod, Jana; Cohn, Stephen M.; Rashid, Qammar; Pernas, Francisco; Ledford, Marlies R.; Gomez-Fein, Eleanor; Lynn, Mauricio.

In: Journal of Trauma - Injury, Infection and Critical Care, Vol. 53, No. 6, 01.12.2002, p. 1053-1057.

Research output: Contribution to journalArticle

Jeroukhimov, I, Jewelewicz, D, Zaias, J, Hensley, G, MacLeod, J, Cohn, SM, Rashid, Q, Pernas, F, Ledford, MR, Gomez-Fein, E & Lynn, M 2002, 'Early injection of high-dose recombinant factor VIIa decreases blood loss and prolongs time from injury to death in experimental liver injury', Journal of Trauma - Injury, Infection and Critical Care, vol. 53, no. 6, pp. 1053-1057.
Jeroukhimov, Igor ; Jewelewicz, Dory ; Zaias, Julia ; Hensley, George ; MacLeod, Jana ; Cohn, Stephen M. ; Rashid, Qammar ; Pernas, Francisco ; Ledford, Marlies R. ; Gomez-Fein, Eleanor ; Lynn, Mauricio. / Early injection of high-dose recombinant factor VIIa decreases blood loss and prolongs time from injury to death in experimental liver injury. In: Journal of Trauma - Injury, Infection and Critical Care. 2002 ; Vol. 53, No. 6. pp. 1053-1057.
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abstract = "Background: 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. Methods: 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 μg/kg, rFVIIa 720 μg/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 μg/kg (p = 0.02, χ2). Blood loss was decreased in the rFVIIa 720 μg/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 μg/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. Conclusion: 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.",
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T1 - Early injection of high-dose recombinant factor VIIa decreases blood loss and prolongs time from injury to death in experimental liver injury

AU - Jeroukhimov, Igor

AU - Jewelewicz, Dory

AU - Zaias, Julia

AU - Hensley, George

AU - MacLeod, Jana

AU - Cohn, Stephen M.

AU - Rashid, Qammar

AU - Pernas, Francisco

AU - Ledford, Marlies R.

AU - Gomez-Fein, Eleanor

AU - Lynn, Mauricio

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N2 - Background: 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. Methods: 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 μg/kg, rFVIIa 720 μg/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 μg/kg (p = 0.02, χ2). Blood loss was decreased in the rFVIIa 720 μg/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 μg/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. Conclusion: 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.

AB - Background: 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. Methods: 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 μg/kg, rFVIIa 720 μg/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 μg/kg (p = 0.02, χ2). Blood loss was decreased in the rFVIIa 720 μg/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 μg/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. Conclusion: 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.

KW - Hemorrhage

KW - Hepatic trauma

KW - Liver injury

KW - Recombinant factor VIIa

KW - Shock

KW - Thrombosis

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