Impaired Activity of Blood Coagulant Factor XIII in Patients with Necrotizing Enterocolitis

Guo Zhong Tao; Bo Liu; Rong Zhang; Gigi Liu; Fizan Abdullah; Mary Cay Harris; Mary L. Brandt; Richard A. Ehrenkranz; Corinna Bowers; Camilia R. Martin; R. Lawrence Moss; Karl G. Sylvester

doi:10.1038/srep13119

Impaired Activity of Blood Coagulant Factor XIII in Patients with Necrotizing Enterocolitis

Guo Zhong Tao, Bo Liu, Rong Zhang, Gigi Liu, Fizan Abdullah, Mary Cay Harris, Mary L. Brandt, Richard A. Ehrenkranz, Corinna Bowers, Camilia R. Martin, R. Lawrence Moss, Karl G. Sylvester^*

^*Corresponding author for this work

Surgery

Research output: Contribution to journal › Article › peer-review

9 Scopus citations

Abstract

Necrotizing enterocolitis (NEC) is the most common gastrointestinal (GI) medical/surgical emergency of the newborn and a leading cause of preterm neonate morbidity and mortality. NEC is a challenge to diagnose since it often shares similar clinical features with neonatal sepsis. In the present study, plasma protein profiling was compared among NEC, sepsis and control cohorts using gel electrophoresis, immunoblot and mass spectrometry. We observed significant impairment in the formation of fibrinogen-3 dimers (FGG-dimer) in the plasma of newborns with NEC that could efficiently differentiate NEC and sepsis with a high level of sensitivity and specificity. Interestingly, the impaired FGG-dimer formation could be restored in NEC plasma by the addition of exogenous active factor XIII (FXIII). Enzymatic activity of FXIII was determined to be significantly lower in NEC subject plasma for crosslinking FGG when compared to sepsis. These findings demonstrate a potential novel biomarker and related biologic mechanism for diagnosing NEC, as well as suggest a possible therapeutic strategy.

Original language	English (US)
Article number	13119
Journal	Scientific reports
Volume	5
DOIs	https://doi.org/10.1038/srep13119
State	Published - Aug 17 2015

Funding

This work was supported by grants from the Children’s Surgical Research Program Fund and the Transplantation and Tissue Engineering Center, Packard Foundation for Children’s Health, the FDA UO1FD004194, to K.G.S., and Ikaria Inc. (RLM and KGS).

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title = "Impaired Activity of Blood Coagulant Factor XIII in Patients with Necrotizing Enterocolitis",

abstract = "Necrotizing enterocolitis (NEC) is the most common gastrointestinal (GI) medical/surgical emergency of the newborn and a leading cause of preterm neonate morbidity and mortality. NEC is a challenge to diagnose since it often shares similar clinical features with neonatal sepsis. In the present study, plasma protein profiling was compared among NEC, sepsis and control cohorts using gel electrophoresis, immunoblot and mass spectrometry. We observed significant impairment in the formation of fibrinogen-3 dimers (FGG-dimer) in the plasma of newborns with NEC that could efficiently differentiate NEC and sepsis with a high level of sensitivity and specificity. Interestingly, the impaired FGG-dimer formation could be restored in NEC plasma by the addition of exogenous active factor XIII (FXIII). Enzymatic activity of FXIII was determined to be significantly lower in NEC subject plasma for crosslinking FGG when compared to sepsis. These findings demonstrate a potential novel biomarker and related biologic mechanism for diagnosing NEC, as well as suggest a possible therapeutic strategy.",

author = "Tao, {Guo Zhong} and Bo Liu and Rong Zhang and Gigi Liu and Fizan Abdullah and Harris, {Mary Cay} and Brandt, {Mary L.} and Ehrenkranz, {Richard A.} and Corinna Bowers and Martin, {Camilia R.} and Moss, {R. Lawrence} and Sylvester, {Karl G.}",

note = "Funding Information: This work was supported by grants from the Children{\textquoteright}s Surgical Research Program Fund and the Transplantation and Tissue Engineering Center, Packard Foundation for Children{\textquoteright}s Health, the FDA UO1FD004194, to K.G.S., and Ikaria Inc. (RLM and KGS).",

year = "2015",

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doi = "10.1038/srep13119",

language = "English (US)",

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AU - Tao, Guo Zhong

AU - Liu, Bo

AU - Zhang, Rong

AU - Liu, Gigi

AU - Abdullah, Fizan

AU - Harris, Mary Cay

AU - Brandt, Mary L.

AU - Ehrenkranz, Richard A.

AU - Bowers, Corinna

AU - Martin, Camilia R.

AU - Moss, R. Lawrence

AU - Sylvester, Karl G.

N1 - Funding Information: This work was supported by grants from the Children’s Surgical Research Program Fund and the Transplantation and Tissue Engineering Center, Packard Foundation for Children’s Health, the FDA UO1FD004194, to K.G.S., and Ikaria Inc. (RLM and KGS).

PY - 2015/8/17

Y1 - 2015/8/17

N2 - Necrotizing enterocolitis (NEC) is the most common gastrointestinal (GI) medical/surgical emergency of the newborn and a leading cause of preterm neonate morbidity and mortality. NEC is a challenge to diagnose since it often shares similar clinical features with neonatal sepsis. In the present study, plasma protein profiling was compared among NEC, sepsis and control cohorts using gel electrophoresis, immunoblot and mass spectrometry. We observed significant impairment in the formation of fibrinogen-3 dimers (FGG-dimer) in the plasma of newborns with NEC that could efficiently differentiate NEC and sepsis with a high level of sensitivity and specificity. Interestingly, the impaired FGG-dimer formation could be restored in NEC plasma by the addition of exogenous active factor XIII (FXIII). Enzymatic activity of FXIII was determined to be significantly lower in NEC subject plasma for crosslinking FGG when compared to sepsis. These findings demonstrate a potential novel biomarker and related biologic mechanism for diagnosing NEC, as well as suggest a possible therapeutic strategy.

AB - Necrotizing enterocolitis (NEC) is the most common gastrointestinal (GI) medical/surgical emergency of the newborn and a leading cause of preterm neonate morbidity and mortality. NEC is a challenge to diagnose since it often shares similar clinical features with neonatal sepsis. In the present study, plasma protein profiling was compared among NEC, sepsis and control cohorts using gel electrophoresis, immunoblot and mass spectrometry. We observed significant impairment in the formation of fibrinogen-3 dimers (FGG-dimer) in the plasma of newborns with NEC that could efficiently differentiate NEC and sepsis with a high level of sensitivity and specificity. Interestingly, the impaired FGG-dimer formation could be restored in NEC plasma by the addition of exogenous active factor XIII (FXIII). Enzymatic activity of FXIII was determined to be significantly lower in NEC subject plasma for crosslinking FGG when compared to sepsis. These findings demonstrate a potential novel biomarker and related biologic mechanism for diagnosing NEC, as well as suggest a possible therapeutic strategy.

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Impaired Activity of Blood Coagulant Factor XIII in Patients with Necrotizing Enterocolitis

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