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Treatment of adults with sepsis-induced coagulopathy and purpura fulminans with a plasma-derived protein C concentrate (Ceprotin)®

Disseminated intravascular coagulation (DIC) is a severe complication of sepsis, especially when associated with skin or organ necrosis appearing as purpura fulminans. Several reports described beneficial effects of protein C replacement in preterm neonates, infants, and adults with purpura fulminans. We treated seven adult patients (six female, one male), median age 35 years (range 19–48 years), with DIC and purpura fulminans with a plasma-derived human protein C concentrate (Ceprotin®; Baxter, Vienna, Austria). Three patients had meningococcal, three had pneumococcal, and one had pseudomonas and cytomegaly-virus infections. At admission, all patients had signs of skin necrosis, severe infection and acute illness. Coagulation assays suggested DIC in five patients (median [range]): platelet count 19 (17–23) G/l, fibrinogen 60 (44–103) mg/dl, antithrombin activity 0.47 (0.25–0.76) U/ml, normotest 32 (14–39)%, APTT 88 (42–160) s, D-dimer 66 (3.3–140) ng/ml; the remaining two patients were treated because of typical skin necrosis and meningococcemia alone. Initial protein C activity was reduced to 0.35 (0.2–0.5) U/ml. Five patients had neurologic alterations, five renal failure, three respiratory failure, one a large intrahepatic necrosis. In five patients Ceprotin® was given as a level-adjusted continuous infusion (starting with 10 U/kg per hour) after an initial bolus of 100 U/kg, two patients were treated with bolus infusions (100 U/kg every 8 hours). Additionally, heparin infusions (seven patients), fresh-frozen plasma (five patients), antithrombin concentrates (three patients), fibrinogen concentrates (two patients), low-dose rtPA (two patients), platelet and erythrocyte transfusions, antibiotics, and hydrocortisone (four patients) were given. Protein C activity increased to 1.34–2.0 U/ml in all patients, coagulation abnormalities resolved within 1–6 days. A total of 8000–77,000 U Ceprotin® were given during 1–7 days. One patient died the same day from multiorgan failure, one died 14 days after the end of Ceprotin® infusion from candida sepsis. All other patients survived, three needed amputations of toes, two had no sequels. Our data suggest that Ceprotin® can be a useful hemostatic support in the treatment of adults with severe, life-threatening purpura fulminans, which would have a high mortality with conventional therapy alone. Controlled studies are needed to establish the value of this drug in the treatment of sepsis.

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Schellongowski, P., Bauer, E., Locker, G. et al. Treatment of adults with sepsis-induced coagulopathy and purpura fulminans with a plasma-derived protein C concentrate (Ceprotin)®. Crit Care 7, P021 (2003).

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  • Fibrinogen
  • Antithrombin
  • Disseminate Intravascular Coagulation
  • Disseminate Intravascular Coagulation
  • Skin Necrosis