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

Martin Schreiber, John B. Holcomb, Ulla Hedner, Susan I. Brundage, Joseph M. Macaitis, Nori Aoki, Zhi Hong Meng, David J. Tweardy, Keith Hoots

    Research output: Contribution to journalArticle

    56 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. It has also been shown to reduce bleeding in coagulopathic pigs with Grade V liver injuries when used as an adjunct to packing. This study was performed to determine if rFVIIa would reduce blood loss after a Grade V liver injury in noncoagulopathic pigs when used as sole therapy. STUDY DESIGN: Thirty normothermic animals were randomized to receive either 150 μg/kg of rFVIIa or normal saline intravenously. After laparotomy and splenectomy, a standardized Grade V liver injury was made with a liver clamp. Thirty seconds after injury, blinded therapy was given. Blood loss was measured 15 minutes after injury and the abdomen was closed. Animals were resuscitated to their baseline blood pressure and the study was continued for 2 hours. Serial coagulation parameters were obtained. Following the study period, blood loss was measured and an autopsy was performed. Grossly normal areas of lung were examined for evidence of intravascular thrombosis. RESULTS: Mean Factor VII:C levels increased 155-fold in the treatment group after infusion of rFVIIa. The mean prothrombin time in the treatment group decreased from 9.8 ± 0.4 seconds to 7.3 ± 0.2 seconds and remained significantly different from the control group throughout the study (p <0.01). There were no differences in other coagulation parameters. Mean initial blood loss was 822 ± 266 mL in the treatment group and 768 ± 215 mL in the control group (p = 0.6). Rebleeding blood volume was 397 ± 191 mL in the treatment group and 437 ± 274 mL (p = 0.6) in the control group. Lung histology revealed no evidence of abnormal microvascular thrombosis. CONCLUSIONS: rFVIIa does not reduce blood loss after Grade V liver injury when it is used as sole therapy in warm noncoagulopathic pigs.

    Original languageEnglish (US)
    Pages (from-to)691-697
    Number of pages7
    JournalJournal of the American College of Surgeons
    Volume196
    Issue number5
    DOIs
    StatePublished - May 1 2003

    Fingerprint

    Swine
    Liver
    Wounds and Injuries
    Hemorrhage
    Control Groups
    Therapeutics
    Thrombosis
    Lung
    Factor VII
    Prothrombin Time
    Hemophilia A
    Splenectomy
    recombinant FVIIa
    Blood Volume
    Liver Transplantation
    Abdomen
    Laparotomy
    Autopsy
    Histology
    Fibrosis

    ASJC Scopus subject areas

    • Surgery

    Cite this

    The effect of recombinant factor VIIa on noncoagulopathic pigs with grade V liver injuries. / Schreiber, Martin; Holcomb, John B.; Hedner, Ulla; Brundage, Susan I.; Macaitis, Joseph M.; Aoki, Nori; Meng, Zhi Hong; Tweardy, David J.; Hoots, Keith.

    In: Journal of the American College of Surgeons, Vol. 196, No. 5, 01.05.2003, p. 691-697.

    Research output: Contribution to journalArticle

    Schreiber, M, Holcomb, JB, Hedner, U, Brundage, SI, Macaitis, JM, Aoki, N, Meng, ZH, Tweardy, DJ & Hoots, K 2003, 'The effect of recombinant factor VIIa on noncoagulopathic pigs with grade V liver injuries', Journal of the American College of Surgeons, vol. 196, no. 5, pp. 691-697. https://doi.org/10.1016/S1072-7515(02)01835-5
    Schreiber, Martin ; Holcomb, John B. ; Hedner, Ulla ; Brundage, Susan I. ; Macaitis, Joseph M. ; Aoki, Nori ; Meng, Zhi Hong ; Tweardy, David J. ; Hoots, Keith. / The effect of recombinant factor VIIa on noncoagulopathic pigs with grade V liver injuries. In: Journal of the American College of Surgeons. 2003 ; Vol. 196, No. 5. pp. 691-697.
    @article{0ef83f7eea9f4e2aada549beaca5203f,
    title = "The effect of recombinant factor VIIa on noncoagulopathic pigs with grade V liver injuries",
    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. It has also been shown to reduce bleeding in coagulopathic pigs with Grade V liver injuries when used as an adjunct to packing. This study was performed to determine if rFVIIa would reduce blood loss after a Grade V liver injury in noncoagulopathic pigs when used as sole therapy. STUDY DESIGN: Thirty normothermic animals were randomized to receive either 150 μg/kg of rFVIIa or normal saline intravenously. After laparotomy and splenectomy, a standardized Grade V liver injury was made with a liver clamp. Thirty seconds after injury, blinded therapy was given. Blood loss was measured 15 minutes after injury and the abdomen was closed. Animals were resuscitated to their baseline blood pressure and the study was continued for 2 hours. Serial coagulation parameters were obtained. Following the study period, blood loss was measured and an autopsy was performed. Grossly normal areas of lung were examined for evidence of intravascular thrombosis. RESULTS: Mean Factor VII:C levels increased 155-fold in the treatment group after infusion of rFVIIa. The mean prothrombin time in the treatment group decreased from 9.8 ± 0.4 seconds to 7.3 ± 0.2 seconds and remained significantly different from the control group throughout the study (p <0.01). There were no differences in other coagulation parameters. Mean initial blood loss was 822 ± 266 mL in the treatment group and 768 ± 215 mL in the control group (p = 0.6). Rebleeding blood volume was 397 ± 191 mL in the treatment group and 437 ± 274 mL (p = 0.6) in the control group. Lung histology revealed no evidence of abnormal microvascular thrombosis. CONCLUSIONS: rFVIIa does not reduce blood loss after Grade V liver injury when it is used as sole therapy in warm noncoagulopathic pigs.",
    author = "Martin Schreiber and Holcomb, {John B.} and Ulla Hedner and Brundage, {Susan I.} and Macaitis, {Joseph M.} and Nori Aoki and Meng, {Zhi Hong} and Tweardy, {David J.} and Keith Hoots",
    year = "2003",
    month = "5",
    day = "1",
    doi = "10.1016/S1072-7515(02)01835-5",
    language = "English (US)",
    volume = "196",
    pages = "691--697",
    journal = "Journal of the American College of Surgeons",
    issn = "1072-7515",
    publisher = "Elsevier Inc.",
    number = "5",

    }

    TY - JOUR

    T1 - The effect of recombinant factor VIIa on noncoagulopathic pigs with grade V liver injuries

    AU - Schreiber, Martin

    AU - Holcomb, John B.

    AU - Hedner, Ulla

    AU - Brundage, Susan I.

    AU - Macaitis, Joseph M.

    AU - Aoki, Nori

    AU - Meng, Zhi Hong

    AU - Tweardy, David J.

    AU - Hoots, Keith

    PY - 2003/5/1

    Y1 - 2003/5/1

    N2 - BACKGROUND: Recombinant Factor VIIa (rFVIIa) has been used to decrease bleeding in a number of settings, including hemophilia, liver transplantation, intractable bleeding, and cirrhosis. It has also been shown to reduce bleeding in coagulopathic pigs with Grade V liver injuries when used as an adjunct to packing. This study was performed to determine if rFVIIa would reduce blood loss after a Grade V liver injury in noncoagulopathic pigs when used as sole therapy. STUDY DESIGN: Thirty normothermic animals were randomized to receive either 150 μg/kg of rFVIIa or normal saline intravenously. After laparotomy and splenectomy, a standardized Grade V liver injury was made with a liver clamp. Thirty seconds after injury, blinded therapy was given. Blood loss was measured 15 minutes after injury and the abdomen was closed. Animals were resuscitated to their baseline blood pressure and the study was continued for 2 hours. Serial coagulation parameters were obtained. Following the study period, blood loss was measured and an autopsy was performed. Grossly normal areas of lung were examined for evidence of intravascular thrombosis. RESULTS: Mean Factor VII:C levels increased 155-fold in the treatment group after infusion of rFVIIa. The mean prothrombin time in the treatment group decreased from 9.8 ± 0.4 seconds to 7.3 ± 0.2 seconds and remained significantly different from the control group throughout the study (p <0.01). There were no differences in other coagulation parameters. Mean initial blood loss was 822 ± 266 mL in the treatment group and 768 ± 215 mL in the control group (p = 0.6). Rebleeding blood volume was 397 ± 191 mL in the treatment group and 437 ± 274 mL (p = 0.6) in the control group. Lung histology revealed no evidence of abnormal microvascular thrombosis. CONCLUSIONS: rFVIIa does not reduce blood loss after Grade V liver injury when it is used as sole therapy in warm noncoagulopathic pigs.

    AB - BACKGROUND: Recombinant Factor VIIa (rFVIIa) has been used to decrease bleeding in a number of settings, including hemophilia, liver transplantation, intractable bleeding, and cirrhosis. It has also been shown to reduce bleeding in coagulopathic pigs with Grade V liver injuries when used as an adjunct to packing. This study was performed to determine if rFVIIa would reduce blood loss after a Grade V liver injury in noncoagulopathic pigs when used as sole therapy. STUDY DESIGN: Thirty normothermic animals were randomized to receive either 150 μg/kg of rFVIIa or normal saline intravenously. After laparotomy and splenectomy, a standardized Grade V liver injury was made with a liver clamp. Thirty seconds after injury, blinded therapy was given. Blood loss was measured 15 minutes after injury and the abdomen was closed. Animals were resuscitated to their baseline blood pressure and the study was continued for 2 hours. Serial coagulation parameters were obtained. Following the study period, blood loss was measured and an autopsy was performed. Grossly normal areas of lung were examined for evidence of intravascular thrombosis. RESULTS: Mean Factor VII:C levels increased 155-fold in the treatment group after infusion of rFVIIa. The mean prothrombin time in the treatment group decreased from 9.8 ± 0.4 seconds to 7.3 ± 0.2 seconds and remained significantly different from the control group throughout the study (p <0.01). There were no differences in other coagulation parameters. Mean initial blood loss was 822 ± 266 mL in the treatment group and 768 ± 215 mL in the control group (p = 0.6). Rebleeding blood volume was 397 ± 191 mL in the treatment group and 437 ± 274 mL (p = 0.6) in the control group. Lung histology revealed no evidence of abnormal microvascular thrombosis. CONCLUSIONS: rFVIIa does not reduce blood loss after Grade V liver injury when it is used as sole therapy in warm noncoagulopathic pigs.

    UR - http://www.scopus.com/inward/record.url?scp=0038327506&partnerID=8YFLogxK

    UR - http://www.scopus.com/inward/citedby.url?scp=0038327506&partnerID=8YFLogxK

    U2 - 10.1016/S1072-7515(02)01835-5

    DO - 10.1016/S1072-7515(02)01835-5

    M3 - Article

    C2 - 12742197

    AN - SCOPUS:0038327506

    VL - 196

    SP - 691

    EP - 697

    JO - Journal of the American College of Surgeons

    JF - Journal of the American College of Surgeons

    SN - 1072-7515

    IS - 5

    ER -