Human protein C concentrate in the treatment of purpura fulminans: a retrospective analysis of safety and outcome in 94 pediatric patients.
BACKGROUND
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, 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.
Veldman
Alex
A
Department of Pediatrics, Monash University, Monash Newborn, Monash Medical Centre, Monash Institute for Medical Research, 246 Clayton RD, Clayton 3168, Melbourne, Australia. alex.veldman@monash.edu
Fischer
Doris
D
Wong
Flora Y
FY
Kreuz
Wolfhart
W
Sasse
Michael
M
Eberspächer
Bruno
B
Mansmann
Ulrich
U
Schosser
Rudolf
R
D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D005260:Female; D005343:Fibrinolytic Agents / Q000009:adverse effects / Q000097:blood / Q000627:therapeutic use*; D005858:Germany; D006470:Hemorrhage / Q000139:chemically induced; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007902:Length of Stay; D008297:Male; D011486:Protein C / Q000009:adverse effects / Q000032:analysis / Q000627:therapeutic use*; D055665:Purpura Fulminans / Q000188:drug therapy* / Q000628:therapy; D012042:Registries; D012121:Respiration, Artificial; D012189:Retrospective Studies
D005343:Fibrinolytic Agents; D011486:Protein C