An open-label study of the role of adjuvant hemostatic support with protein C replacement therapy in purpura fulminans-associated meningococcemia

Activated protein C (APC) is a natural anticoagulant that plays a pivotal r ole in coagulation homeostasis. Severe inherited or acquired deficiency res ults in a clinical syndrome called purpura fulminans, In addition, APC also appears to have potent cytokine-modifying properties and is protective in animal models of sepsis. The dual functional properties of APC are particul arly relevant to severe meningococcemia, where acquired PC deficiency is ac companied by multiorgan failure and purpura fulminans, The authors conducte d an open-label prospective study assessing the efficacy of PC replacement therapy in patients with severe meningococcal septicemia, purpura fulminans , and multiorgan failure. The morbidity and mortality were compared with pr edicted morbidity using the Glasgow Meningococcal Septicemia Prognostic Sco re. Thirty-six patients with a mean age of 12 years (range 3 months to 72 y ears) were enrolled in the study. The mean +/- SD for plasma PC was 18 +/- 7 IU/mL. PC was significantly lower than antithrombin or protein S and was also significantly lower than PC levels in a cohort of patients who develop ed meningococcemia without multiorgan failure and purpura fulminans, A tota l of 3 of 36 (8%) patients died, which compares favorably with predicted mo rtality of 18 of 36 (50%), Amputations were required in 4 of 33 (12%) survi vors and in 2 of 31 (6.5%) patients who received PC within 24 hours of admi ssion into the hospital, in comparison with the predicted amputation rate o f II of 33 (30%). In conclusion, PC replacement therapy in severe meningoco ccal septicemia was associated with a reduction in predicted morbidity and mortality. The beneficial effect of PC replacement may reflect both the ant icoagulant and anti-inflammatory properties of the PC pathway. (C) 2000 by The American Society of Hematology.