Severe sepsis – defined by the presence of both infection and a systemic inflammatory response which produce organ failure 750,000 Americans suffer from it each year
It has a High mortality rate
Incidence is rising and is expected to exceed 1 million cases by 2010

Physiologic Derangements Occurring in Severe Sepsis
Overproduction of inflammatory mediators
IL-1, IL-6, TNF
Unopposed microthrombi formation
Result – organ damage
Low oxygen perfusion to major organs
Cytokine-induced apoptosis

General Facts about Protein C
Made by the liver and circulates as a zymogen
Activated by thrombomodulin receptor
Protein C levels are drastically reduced in states of sepsis
Thrombomodulin receptor down regulation occurs in severe sepsis

Mechanism of Action for rhAPC
Drastically reduces production of thrombin
Reduces levels of PAI-1, enhancing tPA’s actions
Anti-inflammatory mechanisms
Reduces cytokine elaboration
Decreases oxidative damage to endothelial cells
Blocks endothelial cell apoptosis

Contraindications
Active internal bleeding
Hx of hemorrhagic stroke in last 3 mths
Hx of intracranial/ intraspinal surgery or severe head trauma in last 2 mths
Trauma with increased risk of life-threatening bleeding
Epidural catheter
Intracranial neoplasm
Mass lesion
Cerebral herniation

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