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Activated protein C: Potential therapy for severe sepsis, thrombosis, and stroke

2002; Elsevier BV; Volume: 39; Issue: 3 Linguagem: Inglês

10.1053/shem.2002.34093

1532-8686

John H. Griffin, Berislav V. Zloković, José A. Fernández,

Blood properties and coagulation

Activated protein C (APC) reduced all-cause 28-day mortality by 19% in patients with severe sepsis (sepsis associated with acute organ dysfunction) in the Protein C Evaluation in Severe Sepsis (PROWESS) trial, leading to recent approval of recombinant APC for treatment of this condition in adults. This review summarizes current knowledge derived from studies of a variety of animal models in which infused human APC demonstrated beneficial activities. Based on in vivo and also in vitro data, APC manifests antithrombotic, profibrinolytic, anti-inflammatory, and antiapoptotic activities. APC is a normal circulating component of plasma, derived from the protein C zymogen, and is thus a natural endogenous protective homeostatic factor. Because of its multiple activities, APC has a potential role in the treatment of complex and challenging medical disorders, including thrombosis and stroke.