Department of Medicine, Division of Critical Care Medicine, UMDNJ-Robert Wood Johnson Medical School at Camden, Cooper University Hospital, Camden, NJ, USA.
Crit Care Med. 2010 Apr;38(4):1092-100. doi: 10.1097/CCM.0b013e3181cf6fbc.
Coagulation activation is an integral part of sepsis pathogenesis. Experimental data suggest that endothelial exposure to hypoxia activates coagulation. We aimed to test the hypothesis that the quantity of exposure to global tissue hypoxia is associated with the degree of coagulation activation during early sepsis resuscitation.
Prospective, multicenter cohort study.
Emergency department and intensive care unit of three academic hospitals.
Inclusion criteria were age older than 17, acute infection with two or more signs of systemic inflammation, hypotension despite fluid challenge (or lactate >4 mM), and continuous central venous oxygen saturation (Scvo2) monitoring for quantitative resuscitation. Exclusion criteria were anticoagulant or blood product administration.
We recorded central venous oxygen saturation continuously for 0 to 6 hrs of resuscitation and calculated the area under the curve for central venous oxygen saturation <70%. We defined hypoxia exposure as exceeding the median area under the curve for the entire cohort. At 0, 6, and 24 hrs, we measured conventional coagulation biomarkers plus thrombin-antithrombin complex, plasmin-antiplasmin complex, tissue plasminogen activator, plasminogen activator inhibitor-1, protein C, antithrombin, and endothelial markers (E-selectin, intracellular adhesion molecule-1, thrombomodulin). We compared changes during 0 to 6 hrs and 0 to 24 hrs in biomarkers between hypoxia exposure and nonexposure groups. We enrolled 40 patients (60% requiring vasopressors; 30% mortality). We found that exposure to hypoxia alone was not associated with a significant degree of coagulation activation. However, in secondary analyses we found that exposure to arterial hypotension induced E-selectin and thrombin-antithrombin complex, whereas concomitant exposure to both hypotension and hypoxia was associated with amplification of E-selectin and thrombomodulin, and a reduction in protein C.
In this sample of patients undergoing quantitative resuscitation for sepsis, we found that exposure to global tissue hypoxia (as quantified by low central venous oxygen saturation) was not associated with major coagulation activation. Further investigation to elucidate the clinical factors that trigger or intensify the procoagulant response to sepsis is warranted.
凝血激活是脓毒症发病机制的一个组成部分。实验数据表明，内皮细胞暴露于缺氧会激活凝血。我们旨在检验这样一个假设，即全身组织缺氧的暴露量与脓毒症复苏早期凝血激活的程度有关。
前瞻性、多中心队列研究。
三所学术医院的急诊室和重症监护病房。
纳入标准为年龄大于 17 岁，急性感染伴有全身炎症的两个或更多体征，液体复苏后仍有低血压（或乳酸>4 mM），以及持续的中心静脉血氧饱和度（Scvo2）监测以进行定量复苏。排除标准为抗凝或血液制品的应用。
我们连续记录复苏 0 至 6 小时的中心静脉血氧饱和度，并计算中心静脉血氧饱和度<70%的曲线下面积。我们将缺氧暴露定义为超过整个队列曲线下面积的中位数。在 0、6 和 24 小时时，我们测量了常规凝血生物标志物加上凝血酶-抗凝血酶复合物、纤溶酶-抗纤溶酶复合物、组织型纤溶酶原激活物、纤溶酶原激活物抑制剂-1、蛋白 C、抗凝血酶和内皮标志物（E-选择素、细胞间黏附分子-1、血栓调节蛋白）。我们比较了缺氧暴露组和非暴露组在 0 至 6 小时和 0 至 24 小时期间生物标志物的变化。我们纳入了 40 名患者（60%需要升压药；30%死亡率）。我们发现，单独暴露于缺氧与显著程度的凝血激活无关。然而，在二次分析中，我们发现动脉低血压单独暴露会导致 E-选择素和凝血酶-抗凝血酶复合物的增加，而同时暴露于低血压和缺氧会导致 E-选择素和血栓调节蛋白的放大，以及蛋白 C 的减少。
在接受脓毒症定量复苏的患者样本中，我们发现全身组织缺氧（通过低中心静脉血氧饱和度来量化）与主要凝血激活无关。需要进一步研究阐明触发或加剧脓毒症促凝反应的临床因素。
