After Xigris®, what is the future for drugs targeting haemostasis in sepsis treatment?

Abstract

Treatment of severe sepsis with activated protein C (Xigris®) has generated great hopes but has also been a subject of controversy. The rational for its evaluation in this indication was based on the increasing knowledge regarding severe sepsis pathophysiology, which has clearly highlighted a reciprocal runaway between inflammation and coagulation processes in these patients. Activated protein C, like other coagulation inhibitors, possesses anti-inflammatory properties in addition to their anticoagulant activity, making them attractive candidates in this indication. However, after Xigris® withdrawal and the negative results of phase III trials evaluating two other inhibitors, tissue factor pathway inhibitor (TFPI) and antithrombin, is there still a place for new drugs targeting haemostasis? The use of soluble thrombomodulin, development of optimized variants of activated protein C as well as inhibitors of both tissue factor-FVIIa and FXIIa-FXIa axes are currently under evaluation.