The effect of recombinant factor VIIa on coagulopathic pigs with grade V liver injuries

Martin Schreiber, John B. Holcomb, Ulla Hedner, Susan I. Brundage, Joseph M. Macaitis, Keith Hoots, Steven N. Vaslef, Ron Gross, James G. Tyburski, Erik S. Barquist, Martin A. Schreiber

    Research output: Contribution to journalArticle

    109 Citations (Scopus)

    Abstract

    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 μg/kg of rFVIIa, 720 μg/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°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-μg/kg group than in the 180-μg/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. Conclusion: 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.

    Original languageEnglish (US)
    Pages (from-to)252-259
    Number of pages8
    JournalJournal of Trauma - Injury, Infection and Critical Care
    Volume53
    Issue number2
    StatePublished - Aug 2002

    Fingerprint

    Swine
    Liver
    Wounds and Injuries
    Control Groups
    Hemostatics
    Hemorrhage
    Laparotomy
    Arterial Pressure
    Therapeutics
    Temperature
    Prothrombin Time
    Hemophilia A
    Porifera
    Splenectomy
    Blood Volume
    Resuscitation
    Pharmaceutical Preparations
    Liver Transplantation
    Abdomen
    recombinant FVIIa

    Keywords

    • Coagulopathy
    • Hemorrhage
    • Hypothermia
    • Liver injury
    • Recombinant factor VIIa
    • Swine

    ASJC Scopus subject areas

    • Surgery

    Cite this

    Schreiber, M., Holcomb, J. B., Hedner, U., Brundage, S. I., Macaitis, J. M., Hoots, K., ... Schreiber, M. A. (2002). The effect of recombinant factor VIIa on coagulopathic pigs with grade V liver injuries. Journal of Trauma - Injury, Infection and Critical Care, 53(2), 252-259.

    The effect of recombinant factor VIIa on coagulopathic pigs with grade V liver injuries. / Schreiber, Martin; Holcomb, John B.; Hedner, Ulla; Brundage, Susan I.; Macaitis, Joseph M.; Hoots, Keith; Vaslef, Steven N.; Gross, Ron; Tyburski, James G.; Barquist, Erik S.; Schreiber, Martin A.

    In: Journal of Trauma - Injury, Infection and Critical Care, Vol. 53, No. 2, 08.2002, p. 252-259.

    Research output: Contribution to journalArticle

    Schreiber, M, Holcomb, JB, Hedner, U, Brundage, SI, Macaitis, JM, Hoots, K, Vaslef, SN, Gross, R, Tyburski, JG, Barquist, ES & Schreiber, MA 2002, 'The effect of recombinant factor VIIa on coagulopathic pigs with grade V liver injuries', Journal of Trauma - Injury, Infection and Critical Care, vol. 53, no. 2, pp. 252-259.
    Schreiber, Martin ; Holcomb, John B. ; Hedner, Ulla ; Brundage, Susan I. ; Macaitis, Joseph M. ; Hoots, Keith ; Vaslef, Steven N. ; Gross, Ron ; Tyburski, James G. ; Barquist, Erik S. ; Schreiber, Martin A. / The effect of recombinant factor VIIa on coagulopathic pigs with grade V liver injuries. In: Journal of Trauma - Injury, Infection and Critical Care. 2002 ; Vol. 53, No. 2. pp. 252-259.
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    abstract = "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 μg/kg of rFVIIa, 720 μg/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°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-μg/kg group than in the 180-μg/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. Conclusion: 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.",
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    AU - Holcomb, John B.

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    AU - Brundage, Susan I.

    AU - Macaitis, Joseph M.

    AU - Hoots, Keith

    AU - Vaslef, Steven N.

    AU - Gross, Ron

    AU - Tyburski, James G.

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