Division of Trauma and Surgical Critical Care, Osaka General Medical Center, Osaka, Japan.
Department of Traumatology and Acute Critical Medicine, Osaka University Graduate School of Medicine, Osaka, Japan.
J Thromb Haemost. 2018 Mar;16(3):462-464. doi: 10.1111/jth.13946. Epub 2018 Jan 29.
Selecting an appropriate target population is essential to maximize survival benefits of anticoagulant therapy against sepsis. Our meta-analysis of three populations with sepsis and nationwide observational study in Japan showed that anticoagulants improved mortality only in sepsis-induced disseminated intravascular coagulation (DIC) but not in non-DIC. This divergent effect was physiologically explained by host-protective immune responses of local thrombosis, which are mandatory in the early stage of sepsis. Meanwhile, the lack of definitive evidence for survival benefit provided by several trials of sepsis-induced DIC indicated that this condition was probably not the best target of anticoagulants. Our multicenter cohort study including only patients with sepsis-induced DIC showed a survival benefit from recombinant thrombomodulin only in patients with high disease severity. Thus, we believe that the population with sepsis and DIC and high disease severity is the optimal target for anticoagulant therapy. Anticoagulant therapy without appropriate target selection should be avoided because of the increased risk of bleeding with no survival benefit.
选择合适的目标人群对于最大限度地提高抗凝治疗对脓毒症的生存获益至关重要。我们对三个脓毒症人群的荟萃分析和日本全国性观察性研究表明，抗凝剂仅改善脓毒症诱导的弥散性血管内凝血（DIC）患者的死亡率，而不改善非 DIC 患者的死亡率。这种不同的效应可以通过局部血栓形成的宿主保护性免疫反应来从生理学上解释，这种反应在脓毒症的早期阶段是必需的。同时，几项脓毒症诱导性 DIC 试验提供的生存获益的明确证据不足表明，这种情况可能不是抗凝剂的最佳目标。我们的多中心队列研究仅包括脓毒症诱导性 DIC 患者，结果显示重组血栓调节蛋白仅在疾病严重程度高的患者中具有生存获益。因此，我们认为脓毒症和 DIC 以及疾病严重程度高的人群是抗凝治疗的最佳目标。由于没有生存获益而增加出血风险，没有适当的目标选择的抗凝治疗应该避免。
