Iba Toshiaki, Yamada Atsushi, Hashiguchi Naoyuki, Nagaoka Isao
Pol Arch Med Wewn. 2014;124(6):321-8. doi: 10.20452/pamw.2299. Epub 2014 Apr 15.
The severity of sepsis increases along with the degree of coagulation disorder, and a fulminant coagulation abnormality is recognized as disseminated intravascular coagulation (DIC). The mortality in sepsis‑associated DIC remains as high as 40%, which is comparable to that in septic shock. Even though intensive research is ongoing, there is currently no established therapy for this life‑threatening complication. Heparins are the oldest, most popular, and least‑expensive anticoagulants available; however, their usefulness for the treatment of septic DIC has never been proved. Expectations for antithrombin concentrate were once high, but high‑dose antithrombin failed to demonstrate a survival benefit, and global sepsis guidelines no longer recommend its use. Recombinant activated protein C was the only recommended anticoagulant for the treatment of severe sepsis until 2011, but it was subsequently withdrawn from the world market after the failure of the latest clinical trial. Recombinant thrombomodulin is newly developed and has been utilized in Japan since 2008; however, its efficacy has not yet been proved. As shown above, progress has not been as fast as expected, but some new agents are upcoming. The efficacy of anticoagulant therapy for septic DIC has long been discussed and aggressively studied, and we have finally realized that correcting the coagulation disorder is not sufficient to conquer this deadly complication. Since many natural anticoagulants have pleiotropic functions, we need to examine these effects and apply them to the right target at the right timing.
脓毒症的严重程度随着凝血功能障碍程度的增加而加重，暴发性凝血异常被认为是弥散性血管内凝血（DIC）。脓毒症相关DIC的死亡率高达40%，与感染性休克的死亡率相当。尽管正在进行深入研究，但目前对于这种危及生命的并发症尚无既定的治疗方法。肝素是最古老、最常用且最便宜的抗凝剂；然而，其对脓毒症性DIC的治疗效果从未得到证实。人们曾对抗凝血酶浓缩物寄予厚望，但高剂量抗凝血酶未能显示出生存获益，全球脓毒症指南不再推荐使用。重组活化蛋白C在2011年之前是唯一被推荐用于治疗严重脓毒症的抗凝剂，但在最新临床试验失败后，它随后退出了全球市场。重组血栓调节蛋白是新开发的，自2008年起在日本使用；然而，其疗效尚未得到证实。如上所述，进展并未如预期般迅速，但一些新药物即将问世。抗凝治疗对脓毒症性DIC的疗效长期以来一直受到讨论并得到积极研究，我们最终意识到，纠正凝血功能障碍不足以攻克这种致命的并发症。由于许多天然抗凝剂具有多效功能，我们需要研究这些作用，并在正确的时机将其应用于正确的靶点。
