Protein C - Role in Medicine

Role in Medicine

For more details on this topic, see drotrecogin alfa.

rhAPC has been the subject of significant controversy since its approval for clinical use in 2001. A 2011 Cochrane review concluded that it does not decrease mortality in severe sepsis or septic shock. It has been noted that rates of severe hemorrhages, drug infusion-related fatal events and termination of infusion due to adverse reactions are all higher in clinical use and open-label trials than in controlled trials. There is a dispute as to whether or not studies after PROWESS confirm its results, and if so, for what subgroups.

Protein C levels have long been noted to predict mortality in patients with sepsis. Because of this, and its pleiotropic anticoagulative and cytoprotective effects, protein C has long been suggested, along with many other drugs, for use in treating patients with severe sepsis. In November of that year, the Food and Drug Administration approved drotrecogin alfa-activated (DrotAA) in the clinical treatment of adults suffering from severe sepsis and with a high risk of death. Drotrecogin alfa-activated is a recombinant form of human activated protein C (rhAPC), i.e. it is a protein produced by recombinant DNA. It is marketed as Xigris by Eli Lilly and Company, but recently recalled and taken off the market.

APC has been studied as way of treating lung injury, after studies showed that in patients with lung injury, reduced APC levels in specific parts of the lungs correlated with worse outcomes. APC also has been considered for use in improving patient outcome in cases of ischemic stroke, a medical emergency in which arterial blockage deprives a region of brain of oxygen, causing tissue death. Promising studies suggest that APC could be coupled with the only currently approved treatment, tissue plasminogen activator (tPA), to protect the brain from tPA's very harmful side effects, in addition to preventing cell death from lack of oxygen (hypoxia). Clinical use of APC has also been proposed for improving the outcome of pancreatic islet transplantation in treating type I diabetes.

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