Impaired Activity of Blood Coagulant Factor XIII in Patients with Necrotizing Enterocolitis.
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-γ 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.
Department of Surgery, Stanford University School of Medicine, Stanford, USA.
Guo-Zhong
GZ
Tao
Department of Surgery, Stanford University School of Medicine, Stanford, USA.
Bo
B
Liu
Department of Surgery, Stanford University School of Medicine, Stanford, USA.
Rong
R
Zhang
1] Department of Surgery, Stanford University School of Medicine, Stanford, USA [2] Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, USA.
Gigi
G
Liu
1] Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, USA [2].
Fizan
F
Abdullah
Department of Pediatrics, Children's Hospital of Philadelphia, Philadelphia, USA.
Mary Cay
MC
Harris
Department of Surgery, Texas Children's Hospital, Baylor College of Medicine, Houston, USA.
Mary L
ML
Brandt
Department of Pediatrics, Yale University School of Medicine, New Haven, USA.
Richard A
RA
Ehrenkranz
1] Division of Pediatric Surgery, Nationwide Children's Hospital, Columbus, USA [2] Department of Surgery, Ohio State College of Medicine, Columbus, USA.
Corinna
C
Bowers
Department of Neonatology, Beth Israel Deaconess Medical Center, Boston, USA.
Camilia R
CR
Martin
1] Division of Pediatric Surgery, Nationwide Children's Hospital, Columbus, USA [2] Department of Surgery, Ohio State College of Medicine, Columbus, USA.
R Lawrence
RL
Moss
1] Department of Surgery, Stanford University School of Medicine, Stanford, USA [2] Lucile Packard Children's Hospital Stanford, Stanford, USA [3] Center for Fetal and Maternal Health, Stanford Children's Health, Stanford, USA.
Karl G
KG
Sylvester
D019540:Area Under Curve; D015415:Biomarkers / Q000097:blood; D002851:Chromatography, High Pressure Liquid; D019281:Dimerization; D004591:Electrophoresis, Polyacrylamide Gel; D020345:Enterocolitis, Necrotizing / Q000097:blood / Q000175:diagnosis* / Q000473:pathology; D005176:Factor XIII / Q000378:metabolism*; D005260:Female; D005340:Fibrinogen / Q000032:analysis*; D006801:Humans; D007223:Infant; D008297:Male; D047928:Premature Birth; D012372:ROC Curve; D018805:Sepsis / Q000175:diagnosis / Q000473:pathology; D053719:Tandem Mass Spectrometry
D015415:Biomarkers; D005340:Fibrinogen; D005176:Factor XIII