Factor XII-mediated contact activation related to poor prognosis in disseminated intravascular coagulation

Hee Sue Park, Ja Yoon Gu, Hyun Ju You, Ji Eun Kim, Hyun Kyung Kim

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Background: The contact system that initiates the intrinsic coagulation pathway plays a role in thrombus ormation. 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 systemfactors including factor XII, activated factor XII (XIIa), prekallikrein, high-molecular-weight kininogen (HMWK), bradykinin, extrinsic factor VII and histoneDNA complex were measured. In an in vitro plasma clotting assay, factor XIIdeficient 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 bradykininwere not significantly different between patientswith andwithout 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. Conclusion: 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 ndependent potential prognostic marker for DIC. Activation of factor XII-mediated coagulation may be a potential therapeutic target in DIC.

Original languageEnglish
Pages (from-to)103-107
Number of pages5
JournalThrombosis Research
Volume138
DOIs
StatePublished - 1 Jan 2016

Fingerprint

Factor XII
Disseminated Intravascular Coagulation
Factor XIIa
Histones
High Molecular Weight Kininogens
Prekallikrein
Factor VII
Blood Coagulation Factors
DNA
Factor XI
Intrinsic Factor
Bradykinin
Silicon Dioxide
Thrombosis

Keywords

  • Contact factor
  • Disseminated intravascular coagulation
  • Histone
  • Intrinsic pathway
  • Neutrophil extracellular traps

Cite this

Park, Hee Sue ; Gu, Ja Yoon ; You, Hyun Ju ; Kim, Ji Eun ; Kim, Hyun Kyung. / Factor XII-mediated contact activation related to poor prognosis in disseminated intravascular coagulation. In: Thrombosis Research. 2016 ; Vol. 138. pp. 103-107.
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abstract = "Background: The contact system that initiates the intrinsic coagulation pathway plays a role in thrombus ormation. 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 systemfactors including factor XII, activated factor XII (XIIa), prekallikrein, high-molecular-weight kininogen (HMWK), bradykinin, extrinsic factor VII and histoneDNA complex were measured. In an in vitro plasma clotting assay, factor XIIdeficient 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 bradykininwere not significantly different between patientswith andwithout 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. Conclusion: 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 ndependent potential prognostic marker for DIC. Activation of factor XII-mediated coagulation may be a potential therapeutic target in DIC.",
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Factor XII-mediated contact activation related to poor prognosis in disseminated intravascular coagulation. / Park, Hee Sue; Gu, Ja Yoon; You, Hyun Ju; Kim, Ji Eun; Kim, Hyun Kyung.

In: Thrombosis Research, Vol. 138, 01.01.2016, p. 103-107.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Factor XII-mediated contact activation related to poor prognosis in disseminated intravascular coagulation

AU - Park, Hee Sue

AU - Gu, Ja Yoon

AU - You, Hyun Ju

AU - Kim, Ji Eun

AU - Kim, Hyun Kyung

PY - 2016/1/1

Y1 - 2016/1/1

N2 - Background: The contact system that initiates the intrinsic coagulation pathway plays a role in thrombus ormation. 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 systemfactors including factor XII, activated factor XII (XIIa), prekallikrein, high-molecular-weight kininogen (HMWK), bradykinin, extrinsic factor VII and histoneDNA complex were measured. In an in vitro plasma clotting assay, factor XIIdeficient 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 bradykininwere not significantly different between patientswith andwithout 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. Conclusion: 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 ndependent potential prognostic marker for DIC. Activation of factor XII-mediated coagulation may be a potential therapeutic target in DIC.

AB - Background: The contact system that initiates the intrinsic coagulation pathway plays a role in thrombus ormation. 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 systemfactors including factor XII, activated factor XII (XIIa), prekallikrein, high-molecular-weight kininogen (HMWK), bradykinin, extrinsic factor VII and histoneDNA complex were measured. In an in vitro plasma clotting assay, factor XIIdeficient 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 bradykininwere not significantly different between patientswith andwithout 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. Conclusion: 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 ndependent potential prognostic marker for DIC. Activation of factor XII-mediated coagulation may be a potential therapeutic target in DIC.

KW - Contact factor

KW - Disseminated intravascular coagulation

KW - Histone

KW - Intrinsic pathway

KW - Neutrophil extracellular traps

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U2 - 10.1016/j.thromres.2015.12.011

DO - 10.1016/j.thromres.2015.12.011

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