Sepsis and disseminated intravascular coagulation

Sepsis is frequently complicated by coagulopathy and, in about 35 % of severe cases, by disseminated intravascular coagulation (DIC). In Japan, aggressive treatment of septic DIC is encouraged using antithrombin and recombinant thrombomodulin. The macrophages, monocytes, and neutrophils are a source of TF and participate in the direct activation of the coagulation cascade in the early phases of sepsis. And activated factor X (FXa), which is involved in hemostasis, thrombogenesis, inflammation, and cellular immune responses, induces TF expression in human peripheral monocytes and, conversely, that inhibition of FXa activity reduces TF expression. Both inflammation and coagulation play an important role in DIC due to sepsis. In addition to inflammatory cytokines (TNF-α, IL-1 and so on), HMGB1 has recently been shown to mediate the lethal late phase of sepsis and caused coagulopathy. TM not only binds HMGB1 but also aids the proteolytic cleavage of HMGB1 by thrombin. There have been many reports of the efficacy of recombinant TM and antithrombin for treatment of septic DIC from Japan. Further investigation of the efficacy of recombinant TM and AT in countries other than Japan, as well as the monitoring of medical costs incurred during hospitalization, will help validate the use of TM and AT for treatment of septic DIC.