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Based on a single 2001 study, the U.S. FDA approved recombinant activated protein C (drotrecogin alfa; Xigris) for patients with severe sepsis (NEJM JW Gen Med Apr 15 2001 and N Engl J Med 2001; 344:699). However, after multiple subsequent trials showed higher rates of bleeding in drotrecogin-treated patients and no mortality benefit, it was taken off the market (NEJM JW Gen Med Aug 15 2012 and N Engl J Med 2012; 366:2055).
Now, a different agent that affects the same pathway has been considered for a more-select population of patients with sepsis. Recombinant human soluble thrombomodulin (rhsTM) binds thrombin and serves as an activation complex to convert protein C to activated protein C. This effect might mitigate the coagulopathy of seps…