Early Detection of Disseminated Intravascular Coagulation During Septic Shock: A Multicenter Prospective Study
Early Detection of Disseminated Intravascular Coagulation During Septic Shock: A Multicenter Prospective Study
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DOI：
10.1097/ccm.0000000000001836
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发表时间：
2016-10-01
影响因子：
8.8
通讯作者：
Boisrame-Helms, Julie
中科院分区：
文献类型：
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作者：
Delabranche, Xavier;Quenot, Jean-Pierre;Boisrame-Helms, Julie
目的：感染性休克患者分层不充分可能导致随机临床试验中治疗分配不当，尤其是关于抗凝剂。我们以前报道过内皮源性微粒是脓毒症诱导的弥散性血管内凝血的相关生物标志物。在这个验证队列，我们评估微粒作为替代品的细胞活化，以提高早期弥散性血管内凝血的诊断和患者stratification.Design：前瞻性观察研究在脓毒性休克patients.Settings：四个医疗ICU在大学hospitals.Patients和方法：265例脓毒性休克患者从四个ICU连续入组。根据日本急性医学协会2006评分诊断为弥散性血管内凝血。内皮细胞和白细胞衍生的循环促凝血微粒被分离和定量凝血酶原酶测定在入院时，第3天，和第7天。干预：无。测量和主要结果：二百五十九例患者进行了分析。61例患者在入院时发生弥漫性血管内凝血，32例患者在入院后24小时内发生弥漫性血管内凝血。多因素Logistic回归模型证实内皮细胞来源的微粒与弥散性血管内凝血相关：CD 105（+）-微粒（优势比，2.13）和CD 31（+）-微粒（优势比，0.65）（p < 0.05）。此外，CD 11 a（+）-微粒与白细胞的比率证明白细胞活化（比值比，1.59; p < 0.05）。在排除入院时弥散性血管内凝血的患者后，还分析了弥散性血管内凝血的预测。一项新的多元逻辑回归分析表明，CD 105（+）-微粒（> 0.60 nM eq. PhtdSer;优势比为1.67;血小板计数（5127 g/L;比值比，0.99; p < 0.01）和凝血酶原时间（558%;比值比，0.98; p < 0.05）。入院时的综合评分可预测无弥散性血管内凝血（曲线下面积72.9%;特异性71.2%;敏感性71.0%;阴性预测值93.1%，阳性预测值31.0%）。来自内皮细胞和白细胞的促凝血微粒反映了脓毒症期间的血管损伤-在明显的凝血激活之前引起的弥散性血管内凝血。凝血酶原时间、内皮源性CD 105（+）微粒和入院时血小板计数的组合可以预测是否存在弥散性血管内凝血，并允许在未来的随机临床试验中更好地分层。
Objectives: Inadequate stratification of septic shock patients may result in inappropriate treatment allocation in randomized clinical trials, especially regarding anticoagulant. We previously reported that endothelial-derived microparticles are relevant biomarkers of sepsis-induced disseminated intravascular coagulation. In this validation cohort, we assess microparticles as surrogates of cell activation to improve early disseminated intravascular coagulation diagnosis and patient stratification.Design: Prospective observational study in septic shock patients.Settings: Four medical ICUs in university hospitals.Patients and Methods: Two hundred sixty-five patients with septic shock from four ICUs were consecutively enrolled. Disseminated intravascular coagulation was diagnosed according to Japanese Association for Acute Medicine 2006 score. Endothelial- and leukocyte-derived circulating procoagulant microparticles were isolated and quantified by prothrombinase assay at admission, day 3, and day 7.Intervention: None.Measurements and Main Results: Two hundred fifty-nine patients were analyzed. Sixty-one had disseminated intravascular coagulation at admission, and 32 developed disseminated intravascular coagulation during the first 24 hours after admission. Multiple logistic regression model confirmed that endothelial cell-derived microparticles were associated with disseminated intravascular coagulation: CD105(+)-microparticles (odds ratio, 2.13) and CD31(+)-microparticles (odds ratio, 0.65) (p < 0.05). Furthermore, CD11a(+)-microparticles to leukocyte ratio evidenced leukocyte activation (odds ratio, 1.59; p < 0.05). Prediction of disseminated intravascular coagulation was also analyzed after exclusion of patients with disseminated intravascular coagulation at admission. A new multiple logistic regression analysis demonstrated the association of CD105(+)-microparticles (> 0.60 nM eq. PhtdSer; odds ratio, 1.67; p< 0.01), platelets count (5 127 g/L; odds ratio, 0.99; p < 0.01), and prothrombin time (5 58%; odds ratio, 0.98; p < 0.05) with disseminated intravascular coagulation. A combining score at admission is predictive of the absence of disseminated intravascular coagulation (area under the curve, 72.9%; specificity, 71.2%; sensitivity, 71.0%, with a negative predictive value of 93.1% and a positive predictive value of 31.0%).Conclusions: Procoagulant microparticles from endothelial cells and leukocytes reflect a vascular injury during sepsis-induced disseminated intravascular coagulation that precedes obvious activation of coagulation. A combination of prothrombin time, endothelium-derived CD105(+)-microparticles, and platelet count at admission could predict the absence of disseminated intravascular coagulation and allow a better stratification in future randomized clinical trials.