title: Factor XII-mediated contact activation related to poor prognosis in disseminated intravascular coagulation.
abstract: BACKGROUND
  The contact system that initiates the intrinsic coagulation pathway plays a role in thrombus formation. Since neutrophil extracellular traps (NET), which are mainly composed of histone and DNA, are actively formed in disseminated intravascular coagulation (DIC) and the NET can activate factor XII, it is plausible that a NET component strongly activates the contact system in patients with DIC.
  
  
  METHODS
  In 146 patients suspected of having DIC, the plasma levels of contact system factors including factor XII, activated factor XII (XIIa), prekallikrein, high-molecular-weight kininogen (HMWK), bradykinin, extrinsic factor VII and histone–DNA complex were measured. In an in vitro plasma clotting assay, factor XII–deficient plasma was stimulated with silica or histone.
  
  
  RESULTS
  The levels of not only extrinsic coagulation factor VII but also intrinsic coagulation factors including factors XI and XII were significantly decreased in patients with overt DIC in comparison with those with no overt DIC. Factor XIIa and histone-DNA complex were also significantly increased in patients with overt DIC. However,HMWK, prekallikrein and bradykin inw ere not significantly different between patients with and without overt DIC. Interestingly, factors XII and XIIa were revealed as significantly independent potential prognostic markers for DIC. The histone-DNA complex level significantly contributed to the factor XIIa level (20.6%). In an in vitro clotting assay, histone, a major component of NET, activated coagulation that was dependent, in part, on the presence of factor XII.
  
  
  CONCLUSIONS
  These findings suggest that active NET formation can induce factor XII-mediated coagulation activation in patients with DIC with poor prognosis. The resulting factor XIIa release can be used as an independent potential prognostic marker for DIC. Activation of factor XII-mediated coagulation may be a potential therapeutic target in DIC,
authors.affiliation: Department of Laboratory Medicine and Cancer Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea.
authors.forename: Hee Sue
authors.initials: HS
authors.lastname: Park
authors.affiliation: Department of Laboratory Medicine and Cancer Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea.
authors.forename: JaYoon
authors.initials: J
authors.lastname: Gu
authors.affiliation: Department of Laboratory Medicine and Cancer Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea.
authors.forename: Hyun Ju
authors.initials: HJ
authors.lastname: You
authors.affiliation: Department of Laboratory Medicine and Cancer Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea.
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, Republic of Korea. Electronic address: lukekhk@snu.ac.kr.
authors.forename: Hyun Kyung
authors.initials: HK
authors.lastname: Kim
mesh_terms: D000328:Adult; D000368:Aged; D001777:Blood Coagulation; D004211:Disseminated Intravascular Coagulation / Q000097:blood* / Q000175:diagnosis*; D005174:Factor XII / Q000032:analysis*; D015956:Factor XIIa / Q000032:analysis; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011379:Prognosis
chemical_list: D005174:Factor XII; D015956:Factor XIIa
keywords: Contact factor; Disseminated intravascular coagulation; Histone; Intrinsic pathway; Neutrophil extracellular traps