The anticoagulant therapy for sepsis-associated disseminated intravascular coagulation

Abstract

Sepsis is a leading cause of death in critically ill patients and it requires multidisciplinary treatment. The effects of anticoagulant therapy for sepsis-associated disseminated intravascular coagulation have been long discussed and intensively studied. The recent topics in this area are 1) withdrawal of recombinant activated protein C(rAPC) from the market, 2) potential efficacy of the supplement-dose of antithrombin, 3) success of the recombinant thrombomodulin in a Phase 2B trial.

rAPC had been the only anticoagulant recommended in the global guideline for the treatment of severe sepsis (Surviving Sepsis Campaign guidelines (SSCG) 2008). However, the recommendation was withdrawn from the latest version of SSCG after rAPC could not demonstrate sufficient efficacy in the most recent randomized controlled trial. Antithrombin concentrate is another anticoagulant which can be effective for sepsis-associated disseminated intravascular coagulation (DIC). However, high-dose antithrombin is recommended not to be used in SSCG 2012 since it did not show any survival benefit and increased the bleeding risks in severe sepsis. Nonetheless, a recent clinical study reported the potential efficacy of supplement-dose antithrombin in septic DIC. Recombinant thrombomodulin has been newly developed and its efficacy for DIC was reported. A recent multinational randomized controlled trial has also demonstrated the potential efficacy of this therapeutic agent for septic DIC and a Phase 3 study is currently underway.