Discuss the Beneficial Effects of Activated Protein C in the Treatment of Severe Sepsis

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Sepsis is a potentially fatal medical condition where the blood is overwhelmed by the presence of bacteria; activating the immune response and potentially causing organ dysfunction due to the disruption of homeostasis, tissue perfusion and limited oxygen supply. Systemic inflammatory response syndrome can be a key to the recognition of the illness. This condition can be treated with antibiotics intravenously or by draining the infected fluid. However, treating the infection with appropriate anti-microbial medication does not always cure the illness. Understanding the activation of inflammation, coagulation and fibrinolysis in the pathophysiology of sepsis, has allowed further research and development of therapeutic agents in its clinical treatment (Della, 2012).

In response to pathogens infecting the body, leukocytes release cytokines, some examples are interleukin-1, 6 and tumour necrosis factor α (Bernard, 2001). These can cause extensive activation of coagulation and decreased fibrinolysis; thus the equilibrium of the body normally regulated by homeostasis is altered (van Deventer, 1990). Coagulation is activated by stimulating factors leading to the generation of thrombin. Thrombin can stimulate inflammatory pathways, thus reducing fibrinolysis further. However, the activation is reduced in sepsis. One anticoagulant system that regulates thrombin formation is Protein C; which is converted to its activated form by thrombin. Thus, Activated Protein C (APC) alters the coagulation system, and in turn prevents thrombosis and promotes fibrinolysis (Esmon, 1989).

Protein C is a naturally occurring anti-coagulant with key pathways that are beneficial in the treatment of sepsis; such as the cytoprotective mechanisms which include ant...

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...cts of recombinant human activated protein C in a ewe model of septic shock. Crit Care Med. ;35(11):2594-600.

van Deventer SJH, Bluller HR, ten Cate JW, Aarden LA, Hack CE, Sturk A. (1990) Experimental endotoxemia in humans: analysis of cytokine release and coagulation, fibrinolytic, and complement pathways. Blood. ;76:2520–2528

Hancock WW, Bach FH. (1997)Immunobiology and therapeutic applications of protein C/protein S/thrombomodulin in human and experimental allo-transplantation and xenotransplantation. Trends Cardiovasc Med. ;7:174–183.

Neyrinck AP, Liu KD, Howard JP, Matthay MA. (2009) Protective mechanisms of activated protein C in severe inflammatory disorders. Br J Pharmacol. ;158(4): 1034–1047

Bernard GR, Vincent JL, Laterre PF, et al. (2001) Efficacy and safety of recombinant human activated protein C for severe sepsis. N Engl J Med. ;344:699–709.

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