Combination of thrombin-antithrombin complex, plasminogen activator inhibitor-1, and protein C activity for early identification of severe coagulopathy in initial phase of sepsis: a prospective observational study.
Combination of thrombin-antithrombin complex, plasminogen activator inhibitor-1, and protein C activity for early identification of severe coagulopathy in initial phase of sepsis: a prospective observational study.
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凝血酶 - 抗凝结蛋白复合物，纤溶酶原激活剂-1和蛋白C活性的结合，可在败血症的初始阶段早期鉴定出严重的凝血病：一项前瞻性观察性研究。
DOI：
10.1186/cc13190
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发表时间：
2014-01-13
期刊：
影响因子：
--
通讯作者：
Sakata Y
中科院分区：
文献类型：
--
作者：
Koyama K;Madoiwa S;Nunomiya S;Koinuma T;Wada M;Sakata A;Ohmori T;Mimuro J;Sakata Y
目前脓毒症凝血功能障碍的早期诊断标准有限。我们推测凝血病在初期已经合并败血症，在血小板和凝血因子逐渐消耗后，严重凝血病或弥散性血管内凝血（DIC）变得明显。为了确定严重凝血功能障碍的早期诊断标志物，我们评估了血浆生物标志物与脓毒症患者随后发生明显DIC的相关性。在一所大学医院的成人ICU中进行了一项单中心、前瞻性观察性研究。血浆样品从ICU入院时的脓毒症患者获得。14种生物标志物，包括全局标志物（血小板计数、凝血酶原时间、活化部分凝血活酶时间、纤维蛋白原和纤维蛋白降解产物（FDP））;凝血酶生成标志物（凝血酶-抗凝血酶复合物（达特）和可溶性纤维蛋白）;抗凝剂标志物（蛋白C（PC）和抗凝血酶）;纤溶标志物（纤溶酶原、α2-纤溶酶抑制剂（PI）、纤溶酶-α2-PI复合物和纤溶酶原激活物抑制剂（派）-1）;和内皮活化的标志物（可溶性E-选择素）。基线时有明显DIC的患者被排除，其余患者在5天内随访明显DIC的发展，在28天内随访死亡率。共有77例患者入组，其中37例在随后的5天内发生了明显的DIC。大多数患者在基线时表现出止血异常，达特为98.7%，FDP为97.4%，PC为88.3%。基线时的大多数止血生物标志物与随后发生的明显DIC显著相关。值得注意的是，达特、派-1和PC可很好地区分有和无明显DIC的患者（受试者工作特征曲线下面积（AUROC），0.77（95%置信区间，0.64 - 0.86）; 0.87（0.78至0.92）; 0.85（0.76至0.91）），并且将三者一起使用，显著改善了AUROC高达0.95（与达特、派-1和PC相比）。在显性DIC的重要诊断标志物中，达特和派-1也是28天死亡率的良好预测因子（AUROC，分别为0.77和0.81）。ICU入院时严重凝血和纤溶异常与随后发生的明显DIC相关。达特、派-1和PC活性的单一测量可以在脓毒症病程早期识别持续严重凝血病的患者。
Current criteria for early diagnosis of coagulopathy in sepsis are limited. We postulated that coagulopathy is already complicated with sepsis in the initial phase, and severe coagulopathy or disseminated intravascular coagulation (DIC) becomes overt after progressive consumption of platelet and coagulation factors. To determine early diagnostic markers for severe coagulopathy, we evaluated plasma biomarkers for association with subsequent development of overt DIC in patients with sepsis. A single-center, prospective observational study was conducted in an adult ICU at a university hospital. Plasma samples were obtained from patients with sepsis at ICU admission. Fourteen biomarkers including global markers (platelet count, prothrombin time, activated partial thromboplastin time, fibrinogen and fibrin degradation product (FDP)); markers of thrombin generation (thrombin-antithrombin complex (TAT) and soluble fibrin); markers of anticoagulants (protein C (PC) and antithrombin); markers of fibrinolysis (plasminogen, α2-plasmin inhibitor (PI), plasmin-α2-PI complex, and plasminogen activator inhibitor (PAI)-1); and a marker of endothelial activation (soluble E-selectin) were assayed. Patients who had overt DIC at baseline were excluded, and the remaining patients were followed for development of overt DIC in 5 days, and for mortality in 28 days. A total of 77 patients were enrolled, and 37 developed overt DIC within the following 5 days. Most patients demonstrated hemostatic abnormalities at baseline with 98.7% TAT, 97.4% FDP and 88.3% PC. Most hemostatic biomarkers at baseline were significantly associated with subsequent development of overt DIC. Notably, TAT, PAI-1 and PC discriminated well between patients with and without developing overt DIC (area under the receiver operating characteristic curve (AUROC), 0.77 (95% confidence interval, 0.64 to 0.86); 0.87 (0.78 to 0.92); 0.85 (0.76 to 0.91), respectively), and using the three together, significantly improved the AUROC up to 0.95 (vs. TAT, PAI-1, and PC). Among the significant diagnostic markers for overt DIC, TAT and PAI-1 were also good predictors of 28-day mortality (AUROC, 0.77 and 0.81, respectively). Severe coagulation and fibrinolytic abnormalities on ICU admission were associated with subsequent development of overt DIC. A single measurement of TAT, PAI-1, and PC activity could identify patients with ongoing severe coagulopathy, early in the course of sepsis.
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DOI：
10.1097/01.ta.0000251420.41427.d3
发表时间：
2007-11-01
影响因子：
--
作者：
Iba, Toshiaki;Gando, Satoshi;Shimazaki, Shuji
通讯作者：
Shimazaki, Shuji
影响因子：
6.7
作者：
Egi, Moritoki;Morimatsu, Hiroshi;Morita, Kiyoshi
通讯作者：
Morita, Kiyoshi
影响因子：
8.8
作者：
Kinasewitz, GT;Zein, JG;Taylor, FB
通讯作者：
Taylor, FB
DOI：
10.1186/cc2459
发表时间：
2004-04
期刊：
Critical care (London, England)
影响因子：
--
作者：
Kinasewitz GT;Yan SB;Basson B;Comp P;Russell JA;Cariou A;Um SL;Utterback B;Laterre PF;Dhainaut JF;PROWESS Sepsis Study Group
通讯作者：
PROWESS Sepsis Study Group
影响因子：
9.6
作者：
LORENTE, JA;GARCIAFRADE, LJ;GARCIAAVELLO, A
通讯作者：
GARCIAAVELLO, A