[Activated protein C (the impact of PROWESS trial)]

The inflammatory response in severe sepsis is integrally linked to procoagulant activity and endothelial activation. The abnormalities in the microcirculation results in the development of septic organ dysfunction. The natural anticoagulant activated protein C is expected not only to improve the unbalanced coagulation/fibrinolysis system, but also to modulate the endothelial function, and to express the anti-inflammatory properties. To certify these effects, a large scale, multiple center, randomized, placebo controlled phase 3 trial (PROWESS trial) has been conducted. The results showed the statistically significant improved survival in patients with sepsis induced organ dysfunction (absolute risk reduction in 6.1%). As a result, activated protein C is recommended in patients at high risk of death such as Acute Physiology and Chronic Health Evaluation II > or = 25. However, since bleeding risk is reported as an adverse effect, activated protein C is contraindicated in patients with bleeding tendency.