Protein C replacement in severe meningococcemia: rationale and clinical experience.
Severe meningococcemia, which is associated with hemodynamic instability, purpura fulminans and disseminated intravascular coagulation, still has a high mortality rate, and patients who survive are often left invalids because of amputations and organ failure. Clinical studies have shown that levels of protein C are markedly decreased in patients with severe meningococcemia and that the extent of the decrease correlates with a negative clinical outcome. There is a growing body of data demonstrating that activated protein C, in addition to being an anticoagulant, is also a physiologically relevant modulator of the inflammatory response. The dual function of protein C may be relevant to the treatment of individuals with severe meningococcal sepsis. In the present review we give a basic overview of the protein C pathway and its anticoagulant activity, and we summarize experimental data showing that activated protein C replacement therapy clearly reduces the mortality rate for fulminant meningococcemia.
Alberio
L
L
Central Haematology Laboratory, University Hospital Inselspital, Bern, Switzerland. lorenzo.alberio@insel.ch
Lämmle
B
B
Esmon
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CT
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000378:metabolism / Q000627:therapeutic use; D000925:Anticoagulants / Q000378:metabolism / Q000627:therapeutic use; D016470:Bacteremia / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism / Q000503:physiopathology; D001777:Blood Coagulation; D006801:Humans; D008589:Meningococcal Infections / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism / Q000503:physiopathology; D011486:Protein C / Q000378:metabolism / Q000502:physiology* / Q000627:therapeutic use
D000894:Anti-Inflammatory Agents, Non-Steroidal; D000925:Anticoagulants; D011486:Protein C