Clinical experience with antithrombin III concentrates in critically ill patients with sepsis and multiple organ failure.

Despite improvements in critical care medicine and the development and aggressive use of potent broad-spectrum anti-microbial agents, mortality due to severe sepsis has not changed during the recent years and still comes to 35% to 45%. For quite a long time our understanding of the pathophysiology of sepsis was mainly focused on endotoxin and proinflammatory cytokines like tumor necrosis factor or interleukin-1. Now it is generally accepted that many signs and symptoms of sepsis are not directly mediated by cytokines but are transmitted through other mediator systems. The coagulation system comes into play especially when the septic process progresses to malperfusion and organ failure. Antithrombin III is an important inhibitor of the intrinsic, extrinsic and common pathway of coagulation. Recently, evidence has been accumulating that there is an additional anti-inflammatory potential of the drug. Currently there are several clinical trials ongoing to investigate whether this effect is of clinical relevance in the treatment of patients with severe sepsis.