Modulating the Endotheliopathy of Trauma: Factor Concentrate vs. Fresh Frozen Plasma

Shibani Pati, Daniel R. Potter, Gail Baikamunova, David H. Farrell, John B. Holcomb, Martin Schreiber

    Research output: Contribution to journalArticle

    31 Citations (Scopus)

    Abstract

    BACKGROUND: Transfusion of balanced ratios of plasma to platelets and red blood cells has been shown to reduce early death from exsanguination in trauma patients. Aside from hemostasis, recent work has shown that plasma reduces vascular endothelial permeability, inflammation and organ edema after hemorrhagic shock, all components of the endotheliopathy of trauma (EOT). We hypothesized that Kcentra could have protective effects on the EOT comparable to FFP. METHODS: In vitro: Endothelial cell (EC) barrier function was assessed by measuring changes in trans-endothelial electrical resistance (TEER) for Kcentra, FFP and albumin. In vivo, a modified Miles assay was used on mice to study the effects of Kcentra, FFP and albumin on vascular permeability induced by VEGF-A. The same groups were studied in a second in vivo model of pulmonary vascular leak induced by hemorrhagic shock (HS) and laparotomy. The identification of proteins in Kcentra was assessed by liquid chromatography/mass spectrometry (LC/MS) RESULTS: We found that FFP and Kcentra inhibit EC permeability. We also found that Kcentra and FFP have equivalent capacity to restore EC adherens junction breakdown induced by VEGF-A. In vivo we found that KCentra and FFP, but not albumin significantly inhibited vascular permeability induced by VEGF-A and HS induced vascular permeability in mice. Investigation of the protein content of Kcentra by mass spectroscopy revealed that there are a number of proteins in Kcentra, derived from plasmathat may have contributory roles in the noted effects of Kcentra on vascular leak. CONCLUSION: Taken together we have demonstrated that FFP and Kcentra inhibit vascular permeability in vivo and in vitro, These beneficial effects of Kcentra may be due in part to modulation of vascular function by soluble factors present in Kcentra aside from the known clotting factors II, VII, IX, and X. The clinical implications of these findings is unknown and warrant further investigation.

    Original languageEnglish (US)
    JournalJournal of Trauma and Acute Care Surgery
    DOIs
    StateAccepted/In press - Jan 21 2016

    Fingerprint

    Capillary Permeability
    Hemorrhagic Shock
    Vascular Endothelial Growth Factor A
    Wounds and Injuries
    Blood Vessels
    Albumins
    Endothelial Cells
    Mass Spectrometry
    Exsanguination
    Adherens Junctions
    Factor VII
    Proteins
    Blood Coagulation Factors
    Intercellular Junctions
    Prothrombin
    Hemostasis
    Electric Impedance
    Liquid Chromatography
    Laparotomy
    Permeability

    ASJC Scopus subject areas

    • Critical Care and Intensive Care Medicine
    • Surgery

    Cite this

    Modulating the Endotheliopathy of Trauma : Factor Concentrate vs. Fresh Frozen Plasma. / Pati, Shibani; Potter, Daniel R.; Baikamunova, Gail; Farrell, David H.; Holcomb, John B.; Schreiber, Martin.

    In: Journal of Trauma and Acute Care Surgery, 21.01.2016.

    Research output: Contribution to journalArticle

    Pati, Shibani ; Potter, Daniel R. ; Baikamunova, Gail ; Farrell, David H. ; Holcomb, John B. ; Schreiber, Martin. / Modulating the Endotheliopathy of Trauma : Factor Concentrate vs. Fresh Frozen Plasma. In: Journal of Trauma and Acute Care Surgery. 2016.
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    abstract = "BACKGROUND: Transfusion of balanced ratios of plasma to platelets and red blood cells has been shown to reduce early death from exsanguination in trauma patients. Aside from hemostasis, recent work has shown that plasma reduces vascular endothelial permeability, inflammation and organ edema after hemorrhagic shock, all components of the endotheliopathy of trauma (EOT). We hypothesized that Kcentra could have protective effects on the EOT comparable to FFP. METHODS: In vitro: Endothelial cell (EC) barrier function was assessed by measuring changes in trans-endothelial electrical resistance (TEER) for Kcentra, FFP and albumin. In vivo, a modified Miles assay was used on mice to study the effects of Kcentra, FFP and albumin on vascular permeability induced by VEGF-A. The same groups were studied in a second in vivo model of pulmonary vascular leak induced by hemorrhagic shock (HS) and laparotomy. The identification of proteins in Kcentra was assessed by liquid chromatography/mass spectrometry (LC/MS) RESULTS: We found that FFP and Kcentra inhibit EC permeability. We also found that Kcentra and FFP have equivalent capacity to restore EC adherens junction breakdown induced by VEGF-A. In vivo we found that KCentra and FFP, but not albumin significantly inhibited vascular permeability induced by VEGF-A and HS induced vascular permeability in mice. Investigation of the protein content of Kcentra by mass spectroscopy revealed that there are a number of proteins in Kcentra, derived from plasmathat may have contributory roles in the noted effects of Kcentra on vascular leak. CONCLUSION: Taken together we have demonstrated that FFP and Kcentra inhibit vascular permeability in vivo and in vitro, These beneficial effects of Kcentra may be due in part to modulation of vascular function by soluble factors present in Kcentra aside from the known clotting factors II, VII, IX, and X. The clinical implications of these findings is unknown and warrant further investigation.",
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    AU - Pati, Shibani

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    AU - Farrell, David H.

    AU - Holcomb, John B.

    AU - Schreiber, Martin

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    N2 - BACKGROUND: Transfusion of balanced ratios of plasma to platelets and red blood cells has been shown to reduce early death from exsanguination in trauma patients. Aside from hemostasis, recent work has shown that plasma reduces vascular endothelial permeability, inflammation and organ edema after hemorrhagic shock, all components of the endotheliopathy of trauma (EOT). We hypothesized that Kcentra could have protective effects on the EOT comparable to FFP. METHODS: In vitro: Endothelial cell (EC) barrier function was assessed by measuring changes in trans-endothelial electrical resistance (TEER) for Kcentra, FFP and albumin. In vivo, a modified Miles assay was used on mice to study the effects of Kcentra, FFP and albumin on vascular permeability induced by VEGF-A. The same groups were studied in a second in vivo model of pulmonary vascular leak induced by hemorrhagic shock (HS) and laparotomy. The identification of proteins in Kcentra was assessed by liquid chromatography/mass spectrometry (LC/MS) RESULTS: We found that FFP and Kcentra inhibit EC permeability. We also found that Kcentra and FFP have equivalent capacity to restore EC adherens junction breakdown induced by VEGF-A. In vivo we found that KCentra and FFP, but not albumin significantly inhibited vascular permeability induced by VEGF-A and HS induced vascular permeability in mice. Investigation of the protein content of Kcentra by mass spectroscopy revealed that there are a number of proteins in Kcentra, derived from plasmathat may have contributory roles in the noted effects of Kcentra on vascular leak. CONCLUSION: Taken together we have demonstrated that FFP and Kcentra inhibit vascular permeability in vivo and in vitro, These beneficial effects of Kcentra may be due in part to modulation of vascular function by soluble factors present in Kcentra aside from the known clotting factors II, VII, IX, and X. The clinical implications of these findings is unknown and warrant further investigation.

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