title: Degradation of cross-linked fibrin by leukocyte elastase as alternative pathway for plasmin-mediated fibrinolysis in sepsis-induced disseminated intravascular coagulation.
abstract: An alternative pathway for fibrinolysis that comprises leukocyte elastase and its interaction with the plasminogen activator-plasmin system has been suggested. Plasma levels of cross-linked fibrin degradation product by leukocyte elastase (e-XDP) were significantly increased in patients with sepsis induced disseminated intravascular coagulation (DIC) compared with healthy subjects (18.6±19.9 vs 0.58±0.47U/mL, p<0.001). Twenty seven unique spots were identified from e-XDP dominant patients by immune-purification and two-dimensional difference gel electrophoresis, and they contained fibrinogen Bβ-chain derived fragments Bβ Asp-164, Ser-200, Gln-301, Ala-354, Ile-484 and γ-chain derivatives γ Val-274 at their amino-termini by acquired and processed tandem mass spectrometer. The Sequential Organ Failure Assessment Scores in patients with e-XDPs levels 3-10U/mL were significantly lower than those with e-XDPs levels -3U/mL, 10-30U/mL, and 30- U/mL. The adjusted odds for 28-day mortality rate in patients with e-XDP levels less than 3U/mL (hazard ratio, 4.432; 95% CI, 1.557-12.615 [p=0.005]) were significantly higher than those in patients with e-XDP levels of 3-10U/mL. These data suggest that leukocyte elastase might contribute to the degradation of cross-linked fibrin in sepsis-induced DIC.
authors.affiliation: Research Division of Cell and Molecular Medicine, Center for Molecular Medicine, Jichi Medical University, Tochigi, Japan. madochan@jichi.ac.jp
authors.forename: Seiji
authors.initials: S
authors.lastname: Madoiwa
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Tanaka
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Nagahama
authors.forename: Momoko
authors.initials: M
authors.lastname: Dokai
authors.forename: Yuji
authors.initials: Y
authors.lastname: Kashiwakura
authors.forename: Akira
authors.initials: A
authors.lastname: Ishiwata
authors.forename: Asuka
authors.initials: A
authors.lastname: Sakata
authors.forename: Atsushi
authors.initials: A
authors.lastname: Yasumoto
authors.forename: Tsukasa
authors.initials: T
authors.lastname: Ohmori
authors.forename: Jun
authors.initials: J
authors.lastname: Mimuro
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Sakata
mesh_terms: D000368:Aged; D004211:Disseminated Intravascular Coagulation / Q000097:blood* / Q000175:diagnosis / Q000209:etiology / Q000378:metabolism; D005260:Female; D005337:Fibrin / Q000378:metabolism*; D005338:Fibrin Fibrinogen Degradation Products / Q000378:metabolism; D005341:Fibrinolysin / Q000378:metabolism*; D005342:Fibrinolysis; D006801:Humans; D019272:Leukocyte Elastase / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D018805:Sepsis / Q000150:complications*
chemical_list: D005338:Fibrin Fibrinogen Degradation Products; D005337:Fibrin; D019272:Leukocyte Elastase; D005341:Fibrinolysin