Degradation of cross-linked fibrin by leukocyte elastase as alternative pathway for plasmin-mediated fibrinolysis in sepsis-induced disseminated intravascular coagulation

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• 作者：Seiji Madoiwa^a ; ^{madochan@jichi.ac.jp} ; Hideyuki Tanaka^b ; Yutaka Nagahama^b ; Momoko Dokai^a ; Yuji Kashiwakura^a ; Akira Ishiwata^a ; Asuka Sakata^a ; Atsushi Yasumoto^a ; Tsukasa Ohmori^a ; Jun Mimuro^a ; Yoichi Sakata^a ;
• 关键词：Disseminated intravascular coagulation ; Sepsis ; Leukocyte elastase-dependent cross-linked fibrin degradation products ; Plasmin ; Prognosis
• 刊名：Thrombosis Research
• 出版年：2011
• 出版时间：April 2011
• 年：2011
• 卷：127
• 期：4
• 页码：349-355
• 全文大小：716 K

文摘

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 ± 0.47 U/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 3-10 U/mL were significantly lower than those with e-XDPs levels -3 U/mL, 10-30 U/mL, and 30- U/mL. The adjusted odds for 28-day mortality rate in patients with e-XDP levels less than 3 U/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 3–10 U/mL. These data suggest that leukocyte elastase might contribute to the degradation of cross-linked fibrin in sepsis-induced DIC.