Gando Satoshi, Hayakawa Mineji, Sawamura Atsushi, Hoshino Hirokatsu, Oshiro Akiko, Kubota Nobuhiko, Jesmin Subrina
Department of Anesthesiology and Critical Care Medicine, Hokkaido University Graduate School of Medicine, N17 W5, Kita-ku, Sapporo 060 Japan.
Thromb Res. 2007;121(1):67-73. doi: 10.1016/j.thromres.2007.02.010. Epub 2007 Mar 29.
We conducted a prospective study to test the hypothesis that the activation of neutrophil elastase-mediated fibrinolysis is insufficient to overcome the fibrinolytic shutdown of disseminated intravascular coagulation (DIC) in patients associated with systemic inflammation.
We investigated 45 consecutive patients with systemic inflammatory response syndrome (SIRS) and sepsis, classified as 11 DIC and 34 non-DIC. Fibrin degradation products by neutrophil elastase (Elastase-XDP) and by plasmin (FDP), cross-linked fibrin degradation products (D-dimer), soluble fibrin, antithrombin, protein C, plasminogen activator inhibitor-1 (PAI-1), and urinary trypsin inhibitor (UTI) were measured within 24 h after the patients met either the SIRS or sepsis criteria (day 0), as well as on days 2 and 4.
In DIC patients, higher levels of soluble fibrin, PAI-1, and FDP and markedly lower levels of antithrombin and protein C were observed in comparison to those in non-DIC patients. DIC patients showed a significantly higher level of peak Elastase-XDP than non-DIC patients (25.7+/-5.9 vs. 16.3+/-2.6 microg/mL, respectively; p=0.0333). However, we could not find any substantial difference in the levels of Elastase-XDP, UTI, and D-dimer on each day during the study period between the two groups. Good correlations were observed between the levels of D-dimer and Elastase-XDP in both patients with and without DIC (r(s)=0.699 and r(s)=0.817, respectively), but the coefficients of determination in both groups showed low values and the slopes of the regression lines were less than 1.0. A multivariate logistic regression analysis showed the elevated peak Elastase-XDP levels to inversely correlate with death. On the other hand, the DIC patients showed a higher number of organ dysfunctions and a poorer prognosis than did the non-DIC patients.
The activation of the neutrophil elastase-mediated fibrinolytic pathway may be insufficient to overcome the fibrinolytic shutdown by PAI-1 and may in part explain the poor prognosis of DIC patients associated with systemic inflammation.
我们进行了一项前瞻性研究，以检验以下假设：在伴有全身炎症的患者中，中性粒细胞弹性蛋白酶介导的纤维蛋白溶解激活不足以克服弥散性血管内凝血（DIC）的纤维蛋白溶解关闭状态。
我们对45例连续的全身炎症反应综合征（SIRS）和脓毒症患者进行了研究，其中11例为DIC患者，34例为非DIC患者。在患者符合SIRS或脓毒症标准后24小时内（第0天）以及第2天和第4天，检测中性粒细胞弹性蛋白酶介导的纤维蛋白降解产物（弹性蛋白酶-XDP）、纤溶酶介导的纤维蛋白降解产物（FDP）、交联纤维蛋白降解产物（D-二聚体）、可溶性纤维蛋白、抗凝血酶、蛋白C、纤溶酶原激活物抑制剂-1（PAI-1）和尿胰蛋白酶抑制剂（UTI）。
与非DIC患者相比，DIC患者的可溶性纤维蛋白、PAI-1和FDP水平较高，而抗凝血酶和蛋白C水平明显较低。DIC患者的弹性蛋白酶-XDP峰值水平显著高于非DIC患者（分别为25.7±5.9 vs. 16.3±2.6 μg/mL；p = 0.0333）。然而，我们未发现两组在研究期间每天的弹性蛋白酶-XDP、UTI和D-二聚体水平有任何实质性差异。在有和无DIC的患者中，D-二聚体和弹性蛋白酶-XDP水平之间均观察到良好的相关性（分别为r(s)=0.699和r(s)=0.817），但两组的决定系数值均较低，回归线斜率均小于1.0。多因素逻辑回归分析显示，弹性蛋白酶-XDP峰值水平升高与死亡呈负相关。另一方面，DIC患者的器官功能障碍数量较多，预后比非DIC患者差。
中性粒细胞弹性蛋白酶介导的纤维蛋白溶解途径的激活可能不足以克服PAI-1引起的纤维蛋白溶解关闭状态，这可能部分解释了伴有全身炎症的DIC患者预后不良的原因。
