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RESEARCH PRODUCT

Plasma derived protein C in severe sepsis: report of two cases

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Severe sepsis is defined as sepsis-associated organ dysfunction, (arterial hypoxemia, acute oliguria, coagulation abnormalities, thrombocytopenia, hyperbilirubinemia), hypoperfusion (hyperlactatemia) and arterial hypotension (mean arterial pressure \70 mmHg, or a systolic blood pressure decrease[40 mmHg) [3, 4]. Septic shock [3, 4] is defined as acute circulatory failure induced by sepsis with hypotension despite adequate fluid resuscitation. A dysfunction of the protein C (PC) pathway is always present in severe sepsis and contributes to the development of coagulopathy and necrosis [12, 13]. This decrease is caused by consumption of protein C during systemic activation of blood coagulation and by reduced hepatic synthesis owing to septic liver dysfunction, but also by degradation of protein C by proteolytic enzymes, such as elastase, released by white blood cells [7]. Numerous studies have demonstrated that decreased circulating levels of protein C in septic patients are associated with increased morbidity and mortality [5, 8, 9, 14, 15]. Most prior clinical trials evaluated pharmacologic agents designed to attenuate the early inflammatory events in sepsis, including glucocorticoids and drugs to neutralize endotoxin, tumor necrosis factor a, or interleukin-1b [18], but none of these treatments were effective, perhaps due to the importance of coagulation disorders in sepsis. A preparation of recombinant human protein C (rhAPC) activated via the thrombin-thrombomodulin complex was found to significantly reduce mortality in a double-blind study carried out on patients with severe sepsis (Prowess Trial) [2]. Plasma-derived PC is produced by specific extractionseparation processes and routinely used to correct the PC activity in patients with hereditary deficiencies. A dozen open studies and only one randomized controlled trial have been published reporting the effects of plasmaderived PC supplementation in patients with meningococcal or bacterial purpura fulminans [11, 19, 21]. We report two cases of severe sepsis treated with plasma derived PC.