Safety of drotrecogin alfa (activated) in the treatment of patients with severe sepsis.

While severe sepsis continues to plague hospitals worldwide, new treatment modalities, including activated recombinant protein C (drotrecogin alfa, Xigris, Lilly), have become a standard treatment alternative in many institutional algorithms. Drotrecogin alfa was shown to have a beneficial effect on mortality versus placebo in the PROWESS (Recombinant Human Activated Protein C Worldwide Evaluation in Severe Sepsis) trial (p = 0.005), but its use is not completely without risk. An increased risk of bleeding, including severe bleeding episodes, exists ranging 3.5 - 5.2% in the drotrecogin alfa treatment group versus 2.0 - 5.0% in the placebo group. Patients at risk include those on concomitant heparin therapy (> 15,000 units/day), those with platelet counts <or= 30,000/mm(3), and those undergoing an invasive procedure during the scheduled infusion period. After almost three years on the US market, the reported incidence of severe bleeding episodes has risen only slightly from the pre-marketing era, at that time notable for restrictive treatment protocols, devoid of at-risk patients. Drotrecogin alfa, while a promising agent for severe sepsis, requires prudent patient evaluation for bleeding risks.