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

Abstract

IntroductionPurpura 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.MethodsIn Germany, patients receiving protein C concentrate (Ceprotin®, 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.ResultsComplete 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).ConclusionsThis 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.

Administration of protein C concentrates in patients without congenital deficit: a systematic review of the literature

“…No other adverse event related to PCc was reported among 340 patients. Bleeding was reported as a complication only in two papers, (20,29) but the authors specified that it was not related to PCc administration. A randomized study performed in children described a mild gastrointestinal hemorrhage occurred in a patient who had severe disseminated intravascular coagulation (DIC) and died of septic shock one day later.…”

“…Sepsis was associated with meningitis, purpura fulminans, and disseminated intravascular coagulation in most cases. All papers but one (29) reported normalization of inflammatory markers and/or of coagulation abnormalities and/or improved outcome. In 233 patients with purpura fulminans and/or meningitis, 26 amputations were described (11%).…”

“…(20) Veldman in his case series described two cases of bleeding: one patient developed epistaxis six hours after PCc administration, the other developed hemorrhage from the throat and the nose immediately after a difficult endotracheal intubation; both patients received the next dose of PCc without complications. (29) …”

“…We previously reviewed (6-8) the published experience with PCc in 66 adults (6)(7)(8)(9)(10)(11)(12)(13)(14) and 118 children (12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25) without congenital defects. Considering the market withdrawal of rhAPC, the recent publication of further case series (26)(27)(28)(29) and the presence of reports (30)(31)(32)(33) that were not identified in the previous reviews, we decided to update the systematic review and concisely summarize the overall results.…”

Streptococcus pneumoniae–induced purpura fulminans in a woman with functional asplenia

“…If administered, it should be used cautiously and preferably in consultation with Hematology. Administration of activated protein C (Xigris) had been shown to be beneficial in patients with PF 16,17 ; however, it has been taken off the market by its manufacturer.…”