PROTEIN C IN SEVERE BURNS

Severe burns are debilitating, life threatening and costly. They are associated with widespread inflammation, insidious coagulopathy, large fluid shifts and variable wound healing. Protein C is a naturally occurring enzyme that circulates in plasma. It plays a central role in inflammation, coagulation, vascular permeability and wound healing. The main aim of this thesis is to outline the scarcely explored relationship between plasma protein C levels and severe burns. Chapter 1 describes the epidemiology and pathophysiology of severe burns, and the function of the protein C system and its relevance to burns. Chapter 2 is the first version of a manuscript subsequently published in Advances in Wound Care. It outlines the assessment and acute management of patients with severe burns. Prominent issues include the potential utility of a variety of biomarkers of burn severity including plasma protein C, the potential superiority of natural colloid solutions over crystalloid solutions in the initial fluid resuscitation phase of management and recent research findings on the operative and perioperative management of patients with severe burns. Emerging methods to facilitate wound healing are described and future research directions are suggested. Chapter 3 is the first version of a manuscript subsequently published in Burns. It describes the major findings of an observational study of patients with severe burns. Key findings include the observation that patients who sustain a severe burn have low levels of plasma protein C and that the protein C level is directly associated with better clinical outcomes. An argument is made that protein C is a potential biomarker of burn severity. Chapter 4 is a general discussion of the potential role of protein C in patients with severe burns, followed by a discussion of pertinent issues with the clinical study described in chapter 3, along with implications for patient management and future research