Optimal patient selection for anticoagulant therapy in sepsis: an evidence-based proposal from Japan

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.