Activated protein C: An emerging therapeutic agent in the prevention of ischemia-reperfusion injury

Free flap necrosis continues to be a significant problem in microvascular surgery. Despite improved microsurgical techniques and equipment, flap loss remains the major operative complication. Although ischemia-induced reperfusion injury remains a significant etiologic factor in flap loss, there is continued interest in endothelial mechanisms that regulate microvascular injury and thrombosis. In recent years, activated protein C (APC) has emerged as a promising therapy in counteracting microcirculatory injury. APC is an anticoagulant that is also involved in signaling pathways that modulate inflammation, apoptosis, and vascular permeability. This article presents the mechanism of action of APC and the benefits of this therapeutic agent, including a possible role in the prevention of free flap ischemia-reperfusion injury.