Universal changes in biomarkers of coagulation and inflammation occur in patients with severe sepsis, regardless of causative micro-organism [ISRCTN74215569].
Universal changes in biomarkers of coagulation and inflammation occur in patients with severe sepsis, regardless of causative micro-organism [ISRCTN74215569].
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DOI：
10.1186/cc2459
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发表时间：
2004-04
期刊：
影响因子：
--
通讯作者：
PROWESS Sepsis Study Group
中科院分区：
文献类型：
--
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
重组人活化蛋白C在严重脓毒症中的全球评估是一项随机、双盲、安慰剂对照、多中心的III期试验，在164个医疗中心的严重脓毒症患者中进行。在这里，我们报告了在研究开始时收集的1690名患者的数据，以及在接下来的7天内接受安慰剂治疗的840名患者的数据（除了通常的标准治疗外）。分析了凝血激活、抗凝、纤溶、内皮损伤和炎症等19项生物标志物，以确定基线值及其随时间变化、28天生存率和感染致病微生物类型之间的关系。19种生物标志物中13种的基线水平与急性生理和慢性健康评估II评分相关，几乎所有患者在基线时都表现出凝血功能障碍、内皮损伤和炎症。在研究开始时，分别有99.7%、95.5%、98.5%和93.4%的患者出现d -二聚体升高、凝血酶-抗凝血酶复合物、IL-6和凝血酶原时间延长。内皮损伤标志物（可溶性血栓调节素）和蛋白C、蛋白S和抗凝血酶缺乏的发生率分别为72%、87.6%、77.8%和81.7%。在44%的患者中观察到纤维蛋白溶解受损（纤溶酶原激活物抑制剂-1升高）。在前7天，凝血酶原时间的增加（在大多数临床环境中很容易测量）在28天死亡的患者中非常明显。在严重脓毒症患者中，炎症和凝血生物标志物的异常与疾病严重程度和死亡率结果有关。凝血功能障碍和炎症是严重脓毒症患者对感染的普遍宿主反应，这在致病微生物组中是相似的。
PROWESS (Recombinant Human Activated Protein C Worldwide Evaluation in Severe Sepsis) was a phase III, randomized, double blind, placebo controlled, multicenter trial conducted in patients with severe sepsis from 164 medical centers. Here we report data collected at study entry for 1690 patients and over the following 7 days for the 840 patients who received placebo (in addition to usual standard of care). Nineteen biomarkers of coagulation activation, anticoagulation, fibrinolysis, endothelial injury, and inflammation were analyzed to determine the relationships between baseline values and their change over time, with 28-day survival, and type of infecting causative micro-organism. Levels of 13 of the 19 biomarkers at baseline correlated with Acute Physiology and Chronic Health Evaluation II scores, and nearly all patients exhibited coagulopathy, endothelial injury, and inflammation at baseline. At study entry, elevated D-dimer, thrombin–antithrombin complexes, IL-6, and prolonged prothrombin time were present in 99.7%, 95.5%, 98.5%, and 93.4% of patients, respectively. Markers of endothelial injury (soluble thrombomodulin) and deficient protein C, protein S, and antithrombin were apparent in 72%, 87.6%, 77.8%, and 81.7%, respectively. Impaired fibrinolysis (elevated plasminogen activator inhibitor-1) was observed in 44% of patients. During the first 7 days, increased prothrombin time (which is readily measurable in most clinical settings) was highly evident among patients who were not alive at 28 days. Abnormalities in biomarkers of inflammation and coagulation were related to disease severity and mortality outcome in patients with severe sepsis. Coagulopathy and inflammation were universal host responses to infection in patients with severe sepsis, which were similar across causative micro-organism groups.
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影响因子：
120.7
作者：
BRUNBUISSON, C;DOYON, F;REGNIER, B
通讯作者：
REGNIER, B
影响因子：
4.8
作者：
Boffa, MB;Hamill, JD;Koschinsky, ML
通讯作者：
Koschinsky, ML
影响因子：
9.6
作者：
LORENTE, JA;GARCIAFRADE, LJ;GARCIAAVELLO, A
通讯作者：
GARCIAAVELLO, A
影响因子：
158.5
作者：
CORRIGAN, JJ;RAY, WL;MAY, N
通讯作者：
MAY, N
影响因子：
8.8
作者：
Angus, D C;Linde-Zwirble, W T;Pinsky, M R
通讯作者：
Pinsky, M R