New therapeutic options for patients with sepsis and disseminated intravascular coagulation

Abstract

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protein C was the only recommended anticoagulant for the treatment of severe sepsis until 2011, but it was subsequently withdrawn from the world market after the failure of the latest clinical trial.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.