title: Circulating levels of DNA-histone complex and dsDNA are independent prognostic factors of disseminated intravascular coagulation.
abstract: BACKGROUND
  Neutrophils can be induced to release DNA combined with histones. The resulting neutrophil extracellular trap (NET) provides a scaffold for growing hemostatic plug. Therefore, the NET formation may be inevitable in clinical conditions that are characterized by formation of vascular thrombi. Thus far, there have been no reports on the clinical significance of NET in disseminated intravascular coagulation (DIC). Therefore, we investigated circulating levels of NET in DIC and analyzed their potential values to assess coagulation severity and predict clinical outcome.
  
  
  METHODS
  The plasma levels of DNA-histone complexes and double-stranded DNA (dsDNA), considered to be in vivo markers of NET, were measured in 199 patients suspected of having DIC and 20 healthy controls.
  
  
  RESULTS
  The circulating levels of DNA-histone complexes and dsDNA were significantly elevated in overt-DIC. The increased levels of these two markers correlated with the severity of coagulopathy including DIC score and D-dimer. Multivariable Cox regression analysis, adjusted for the conventional DIC markers, revealed that elevated DNA-histone complexes and dsDNA are poor independent prognostic markers.
  
  
  CONCLUSIONS
  The circulating levels of NET release reflect the coagulation activation and adverse clinical outcomes in patients with DIC, thereby providing potential clinical relevance for mortality prediction in DIC.
authors.affiliation: Department of Laboratory Medicine and Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea; Cancer Research Institute, Seoul National University College of Medicine, 103 Daehak-ro, Jongno-gu, Seoul 110-799, Korea. Electronic address: youe99@naver.com.
authors.forename: Ji-Eun
authors.initials: JE
authors.lastname: Kim
authors.affiliation: Department of Laboratory Medicine and Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea; Cancer Research Institute, Seoul National University College of Medicine, 103 Daehak-ro, Jongno-gu, Seoul 110-799, Korea. Electronic address: leonuri@naver.com.
authors.forename: Nuri
authors.initials: N
authors.lastname: Lee
authors.affiliation: Department of Laboratory Medicine and Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea; Cancer Research Institute, Seoul National University College of Medicine, 103 Daehak-ro, Jongno-gu, Seoul 110-799, Korea. Electronic address: jayoon20@gamil.com.
authors.forename: Ja-Yoon
authors.initials: JY
authors.lastname: Gu
authors.affiliation: Department of Laboratory Medicine and Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea; Cancer Research Institute, Seoul National University College of Medicine, 103 Daehak-ro, Jongno-gu, Seoul 110-799, Korea. Electronic address: ju4101@naver.com.
authors.forename: Hyun Ju
authors.initials: HJ
authors.lastname: Yoo
authors.affiliation: Department of Laboratory Medicine and Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea; Cancer Research Institute, Seoul National University College of Medicine, 103 Daehak-ro, Jongno-gu, Seoul 110-799, Korea. Electronic address: lukekhk@snu.ac.kr.
authors.forename: Hyun Kyung
authors.initials: HK
authors.lastname: Kim
mesh_terms: D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood; D001777:Blood Coagulation; D004247:DNA / Q000097:blood*; D004211:Disseminated Intravascular Coagulation / Q000097:blood* / Q000175:diagnosis* / Q000401:mortality; D005260:Female; D005338:Fibrin Fibrinogen Degradation Products / Q000096:biosynthesis; D006487:Hemostasis; D006657:Histones / Q000097:blood*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009504:Neutrophils / Q000378:metabolism; D011379:Prognosis; D016016:Proportional Hazards Models; D012372:ROC Curve; D012189:Retrospective Studies; D012680:Sensitivity and Specificity; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D015415:Biomarkers; D005338:Fibrin Fibrinogen Degradation Products; D006657:Histones; C036309:fibrin fragment D; D004247:DNA
keywords: Cancer; Coagulation; D-dimer; DIC score; Neutrophil extracellular trap (NET)