Gando Satoshi, Kameue Takashi, Matsuda Naoyuki, Hayakawa Mineji, Hoshino Hirokatsu, Kato Hirokatsu
Division of Acute and Critical Care Medicine, Department of Anesthesiology and Critical Care Medicine, Hokkaido University School of Medicine, N15, W7, Kita-ku, Sapporo 060 Japan.
Thromb Res. 2005;116(2):91-100. doi: 10.1016/j.thromres.2004.09.022. Epub 2004 Nov 10.
For systematic elucidation of serial changes in neutrophil-endothelial activation markers as well as to investigate the correlationship among the inflammation markers, disseminated intravascular coagulation (DIC), and multiple organ dysfunction syndrome (MODS) in patients with sepsis, we made this prospective study.
Forty-five patients with sepsis, severe sepsis, and septic shock were subdivided into two groups, 27 with DIC and 18 without DIC. Eight normal healthy volunteers served as control subjects. Serial levels of soluble L-, P-, and E-selectins, intercellular adhesion molecule-1 (sICAM-1), vascular cell adhesion molecule-1 (sVCAM-1), thrombomodulin (sTM), and neutrophil elastase were measured within 12 h after the diagnosis of sepsis (day 0) and on days 1-4 after the diagnosis. The numbers of systemic inflammatory response syndrome (SIRS) criteria that patients met and the DIC score were determined simultaneously.
Acute Physiology and Chronic Health Evaluation (APACHE) II score was identical between the two groups. In the DIC patients, higher DIC scores, lower platelet counts, and more maximum numbers of SIRS criteria being met were observed compared with the non-DIC patients. The incidence of MODS and the number of the dysfunctioning organs were higher in the patients with DIC than those without DIC, and the DIC patients had poor outcome. Soluble L-selectin (sL-selectin) levels in both groups tended to be lower than those in the control subjects. All other parameters both in the two groups were continuously higher than those in the control subjects during study period. The levels of soluble E-selectin (sE-selectin), sICAM-1, sVCAM-1, neutrophil elastase, and sTM were more elevated in the DIC patients than those in the non-DIC patients. There were no differences in the sP-selectin levels between the two groups; however, more increased sP-selectin levels per platelet were found in the DIC patients compared with the non-DIC patients. Maximum DIC scores in the DIC group positively correlated with the peak levels of neutrophil elastase and sTM and the number of the dysfunctioning organs.
We found close relations among the neutrophil-endothelial cell interactions, DIC, and MODS in patients with sepsis, severe sepsis, and septic shock. The results indirectly confirm the concept that DIC can produce organ dysfunction and that DIC reflects an inflammatory disorder of the microvasculature.
为系统阐明中性粒细胞 - 内皮细胞激活标志物的系列变化,并研究脓毒症患者炎症标志物、弥散性血管内凝血(DIC)和多器官功能障碍综合征(MODS)之间的相关性,我们开展了这项前瞻性研究。
45例脓毒症、严重脓毒症和脓毒性休克患者被分为两组,27例发生DIC,18例未发生DIC。8名正常健康志愿者作为对照。在脓毒症诊断后12小时内(第0天)以及诊断后的第1 - 4天,连续检测可溶性L - 选择素、P - 选择素和E - 选择素、细胞间黏附分子 - 1(sICAM - 1)、血管细胞黏附分子 - 1(sVCAM - 1)、血栓调节蛋白(sTM)和中性粒细胞弹性蛋白酶的水平。同时确定患者符合的全身炎症反应综合征(SIRS)标准数量和DIC评分。
两组的急性生理与慢性健康状况评分系统(APACHE)II评分相同。与未发生DIC的患者相比,发生DIC的患者DIC评分更高、血小板计数更低,且符合的SIRS标准最大数量更多。发生DIC的患者MODS发生率和功能障碍器官数量高于未发生DIC的患者,且发生DIC的患者预后较差。两组的可溶性L - 选择素(sL - 选择素)水平均低于对照组。在研究期间,两组的所有其他参数均持续高于对照组。发生DIC的患者可溶性E - 选择素(sE - 选择素)、sICAM - sVCAM - 1、中性粒细胞弹性蛋白酶和sTM水平高于未发生DIC的患者。两组间可溶性P - 选择素水平无差异;然而,与未发生DIC的患者相比,发生DIC的患者每血小板的可溶性P - 选择素水平升高更多。DIC组的最大DIC评分与中性粒细胞弹性蛋白酶和sTM的峰值水平以及功能障碍器官数量呈正相关。
我们发现脓毒症、严重脓毒症和脓毒性休克患者中性粒细胞 - 内皮细胞相互作用、DIC和MODS之间存在密切关系。结果间接证实了DIC可导致器官功能障碍且DIC反映微血管炎症紊乱这一概念。