Division of Acute and Critical Care Medicine, Department of Anesthesiology and Critical Care Medicine, Hokkaido University Graduate School of Medicine, N15W7, Kita-ku, Sapporo 060-8638, Japan.
Thromb Res. 2012 Dec;130(6):906-13. doi: 10.1016/j.thromres.2012.01.015. Epub 2012 Feb 19.
We hypothesized that thrombin activatable fibrinolysis inhibitor (TAFI) and the activation of fibrinolysis by both plasmin and neutrophil elastase is insufficient to overcome fibrinolytic shutdown, contributing to multiple organ dysfunction syndrome (MODS) in sepsis-induced disseminated intravascular coagulation (DIC).
Fifty patients with sepsis were prospectively enrolled. The DIC was diagnosed based on the Japanese Association for Acute Medicine (JAAM) DIC and the International Society on Thrombosis and Haemostasis (ISTH) overt DIC criteria.
The JAAM DIC scores were independent predictors of patient death and MODS. The JAAM DIC patients, especially those who met the ISTH overt DIC criteria, showed lower TAFI activity, and higher levels of soluble fibrin, neutrophil elastase, fibrin degradation product by neutrophil elastase (EXDP), plasmin-alpha2 plasmin inhibitor complex (PPIC), tissue plasminogen activator-plasminogen activator inhibitor-1 complex (tPAIC) and D-dimer in comparison with non-DIC patients. There were differences in the levels of soluble fibrin, tPAIC, TAFI activity, and neutrophil elastase between the patients with and without MODS. However, no differences were observed in the levels of PPIC, D-dimer, or EXDP. Soluble fibrin negatively correlated with the TAFI activity. High neutrophil elastase, low TAFI activity and PPIC are independent predictors of patient death and MODS. tPAIC is an independent predictor of elevation of EXDP in DIC patients.
Activation of fibrinolysis both by plasmin and neutrophil elastase cannot overcome fibrinolytic shutdown, leading to MODS and a poor outcome in sepsis-induced DIC. The systemic activation of neutrophils and a low TAFI activity are also involved in the pathogenesis of MODS.
我们假设凝血酶激活的纤溶抑制物（TAFI）和纤溶酶及中性粒细胞弹性蛋白酶激活的纤溶作用不足以克服纤维蛋白溶解抑制，导致脓毒症诱导的弥散性血管内凝血（DIC）中的多器官功能障碍综合征（MODS）。
前瞻性纳入 50 例脓毒症患者。根据日本急性医学协会（JAAM）DIC 和国际血栓与止血学会（ISTH）显性 DIC 标准诊断 DIC。
JAAM DIC 评分是患者死亡和 MODS 的独立预测因子。JAAM DIC 患者，尤其是符合 ISTH 显性 DIC 标准的患者，TAFI 活性较低，可溶性纤维蛋白、中性粒细胞弹性蛋白酶、中性粒细胞弹性蛋白酶降解产物（EXDP）、纤溶酶-α2 纤溶酶抑制剂复合物（PPIC）、组织型纤溶酶原激活物-纤溶酶原激活物抑制剂-1 复合物（tPAIC）和 D-二聚体水平较高。与非 DIC 患者相比，有 MODS 的患者可溶性纤维蛋白、tPAIC、TAFI 活性和中性粒细胞弹性蛋白酶水平存在差异。然而，PPIC、D-二聚体或 EXDP 水平没有差异。可溶性纤维蛋白与 TAFI 活性呈负相关。高中性粒细胞弹性蛋白酶、低 TAFI 活性和 PPIC 是患者死亡和 MODS 的独立预测因子。tPAIC 是 DIC 患者 EXDP 升高的独立预测因子。
纤溶酶和中性粒细胞弹性蛋白酶激活的纤溶作用不能克服纤维蛋白溶解抑制，导致脓毒症诱导的 DIC 中发生 MODS 和不良预后。中性粒细胞的系统激活和 TAFI 活性降低也参与了 MODS 的发病机制。
