Human protein C concentrate in the treatment of purpura fulminans: a retrospective analysis of safety and outcome in 94 pediatric patients

Introduction: Purpura fulminans (PF) is a devastating complication
of uncontrolled systemic inflammation, associated with high
incidence of amputations, skin grafts and death. In this study, we
aimed to clarify the clinical profile of pediatric patients with PF
who improved with protein C (PC) treatment, explore treatment
effects and safety, and to refine the prognostic significance of
protein C plasma levels. Methods: In Germany, patients receiving
protein C concentrate (Ceprotin (R), Baxter AG, Vienna, Austria)
are registered. The database was used to locate all pediatric
patients with PF treated with PC from 2002 to 2005 for this
national, retrospective, multi-centered study. Results: Complete
datasets were acquired in 94 patients, treated in 46 centers with
human, non-activated protein C concentrate for purpura fulminans.
PC was given for 2 days (median, range 1-24 days) with a median
daily dose of 100 IU/kg. Plasma protein C levels increased from a
median of 27% to a median of 71% under treatment. 22.3% of patients
died, 77.7% survived to discharge. Skin grafts were required in
9.6%, amputations in 5.3%. PF recovered or improved in 79.8%,
remained unchanged in 13.8% and deteriorated in 6.4%. Four adverse
events occurred in 3 patients, none classified as severe.
Non-survivors had lower protein C plasma levels (P < 0.05) and
higher prevalence of coagulopathy at admission (P < 0.01). Time
between admission and start of PC substitution was longer in
patients who died compared to survivors (P = 0.03). Conclusions:
This retrospective dataset shows that, compared to historic
controls, only few pediatric patients with PF under PC substitution
needed dermatoplasty and/or amputations. Apart from epistaxis, no
bleeding was observed. Although the data comes from a retrospective
study, the evidence we present suggests that PC had a beneficial
impact on the need for dermatoplasty and amputations, pointing to
the potential value of carrying out a prospective randomised
controlled trial.