• protein C;
  • activation;
  • pharmacokinetics;
  • septic shock

Background:  Activated protein C has recently been shown in a multicentre trial to significantly reduce mortality in patients with septic shock. There are also some case reports and minor studies demonstrating promising results with the unactivated form of protein C. However, in children with severe meningococcal infection, skin biopsies have demonstrated low expression of endothelial thrombomodulin and protein C receptors, suggesting low protein C activation capacity in severe meningococcal sepsis.

Methods:  A patient with meningococcal septic shock was treated with two doses of the unactivated form of protein C, the first during intense activation of the coagulation system and the second during a phase of low grade or no activation. Repeated plasma samples were analysed for protein C concentration, which made it possible to compare pharmacokinetics and half-lives of the two administrations. A shorter half-life during intense coagulation was expected if there was an activation and consumption of the protein C administered.

Results:  The calculated half-lives of protein C during intense and low grade activation were 32 h and 19 h, respectively, a magnitude similar to that reported in protein C-deficient patients without infection.

Conclusion:  The result indicates that whole body utilisation of the unactivated protein C was low. Endothelial impairment of protein C activation does not seem to be restricted to the skin vessels only.