Beyond sepsis: Activated protein C and ischemia-reperfusion injury

OBJECTIVE: To review potential clinical situations beyond sepsis in which activated protein C might be an effective treatment. DATA SOURCE: Published articles between 1970 and 2003 on experimental and clinical studies of activation of both coagulation and inflammation in various disease states. DATA SYNTHESIS AND CONCLUSION: The efficacy of activated protein C in sepsis might rely on the fact that it can modulate both coagulation and inflammation. Therefore, administration of activated protein C could be beneficial in disease states that are also characterized by the simultaneous activation of these systems. Ischemia-reperfusion injury of various organs may represent such a state. Indeed, the involvement of the protein C system has been demonstrated in various experimental studies of ischemia-reperfusion, including studies in renal ischemia-reperfusion syndromes, coronary atherosclerosis and acute coronary syndromes, and intestinal ischemia and reperfusion. In some of these models, activated protein C administration, or other interventions in the protein C system, was shown to be beneficial