Factor XII-mediated contact activation related to poor prognosis in disseminated intravascular coagulation. (February 2016)

• Record Type: Journal Article
• Authors: Park, Hee Sue; Gu, JaYoon; You, Hyun Ju; Kim, Ji-Eun; Kim, Hyun Kyung
• Is Part Of: Thrombosis research. Volume 138(2016)
• Page Start: 103
• Page End: 107
• Publication Date: 2016-02
• Subjects: Intrinsic pathway -- Contact factor -- Neutrophil extracellular traps -- Histone -- Disseminated intravascular coagulation; Thrombosis -- Periodicals; 616.135
• DOI: 10.1016/j.thromres.2015.12.011
• Languages: English
• ISSNs: 0049-3848

Abstract

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 bradykinin were 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. 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 independent potential prognostic marker for DIC. Activation of factor XII-mediated coagulation may be a potential therapeutic target in DIC, Highlights: Factor XIIa is increased in the overt-DIC and it can be used as independent potential prognostic marker for DIC. Active neutrophil extracellular traps (NET) can activate factor XII-mediated coagulation in patients with DIC with poor prognosis. Activation of the factor XII-mediated intrinsic pathway may occur more actively than that of the issue factor-mediated extrinsic pathway, especially in DIC with poor prognosis.