TY - JOUR
T1 - Modulating the endotheliopathy of trauma
T2 - Factor concentrate versus fresh frozen plasma
AU - Pati, Shibani
AU - Potter, Daniel R.
AU - Baimukanova, Gyulnar
AU - Farrel, David H.
AU - Holcomb, John B.
AU - Schreiber, Martin A.
AU - Francisco, San
N1 - Publisher Copyright:
© 2016 Wolters Kluwer Health, Inc. All rights reserved.
PY - 2016
Y1 - 2016
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 (HS), all components of the endotheliopathy of trauma.We hypothesized that Kcentra could have protective effects on the endotheliopathy of trauma comparable with fresh frozen plasma (FFP). METHODS: In vitro, endothelial cell (EC) barrier function was assessed by measuring changes in transendothelial electrical resistance for Kcentra, FFP, and albumin. In vivo, a modifiedMiles 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 HS and laparotomy. The identification of proteins in Kcentra was assessed by liquid chromatography/mass spectrometry. 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 plasma that 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 the 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 are unknown and warrant further investigation.
AB - 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 (HS), all components of the endotheliopathy of trauma.We hypothesized that Kcentra could have protective effects on the endotheliopathy of trauma comparable with fresh frozen plasma (FFP). METHODS: In vitro, endothelial cell (EC) barrier function was assessed by measuring changes in transendothelial electrical resistance for Kcentra, FFP, and albumin. In vivo, a modifiedMiles 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 HS and laparotomy. The identification of proteins in Kcentra was assessed by liquid chromatography/mass spectrometry. 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 plasma that 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 the 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 are unknown and warrant further investigation.
KW - Coagulant function
KW - FFP
KW - Hemorrhagic shock
KW - Kcentra
KW - vascular permeability
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U2 - 10.1097/TA.0000000000000961
DO - 10.1097/TA.0000000000000961
M3 - Article
C2 - 26808040
AN - SCOPUS:84955613207
SN - 2163-0755
VL - 80
SP - 576
EP - 585
JO - Journal of Trauma and Acute Care Surgery
JF - Journal of Trauma and Acute Care Surgery
IS - 4
ER -