title: Use of protein-C concentrate, heparin, and haemodiafiltration in meningococcus-induced purpura fulminans.
abstract: BACKGROUND
  Inflammatory and coagulation processes are both affected in meningococcaemia. Severe acquired protein-C deficiency in meningococcaemia is usually associated with substantial mortality: in survivors, skin grafts, amputation, and end-organ failure are not uncommon. Protein C is a natural anticoagulant and also has important anti-inflammatory activity. We assessed the effects of early replacement therapy with protein-C concentrate together with continuous veno-venous haemodiafiltration and conventional treatment in meningococcaemia.
  
  
  METHODS
  12 patients aged between 3 months and 27 years with meningococcaemia and severe acquired protein-C deficiency (mean 0.20 IU/mL) were studied. All patients had septic shock, widespread purpura, skin necrosis, and disseminated intravascular coagulopathy. After a test dose of protein-C concentrate, patients received a continuous infusion with the dose adjusted daily to keep the plasma concentration between 0.8 and 1.2 IU/mL. 11 patients were given unfractionated intravenous heparin (10-15 IU kg-1 h-1). Nine patients had haemodiafiltration and one had peritoneal dialysis. The Glasgow meningococcal septicaemia prognostic score and the paediatric risk of mortality score predicted a minimum mortality of 80% and 57%, respectively.
  
  
  RESULTS
  No patient died. No adverse reactions to the treatment were seen. Two patients had lower-limb amputations, one of whom had a thrombotic cerebrovascular accident; both patients had received the protein-C concentrate and heparin later than the rest of the group (60 h [16.97] vs 12 h [3.13]). One patient developed chronic renal failure despite receiving protein-C infusion 15 h after admission.
  
  
  CONCLUSIONS
  The acquired severe deficiency of protein C in meningococcaemia contributes to the pathogenesis of the thrombotic necrotic lesions in the skin and other organs and probably has an important role in the inflammatory response. Protein-C therapy is merely one approach to improve the host response in this syndrome. We suggest that a double-blind, randomised, controlled multicentre trial is needed to confirm our results.
authors.affiliation: Department of Paediatric Haematology, National Children's Hospital, Dublin, Ireland.
authors.forename: O P
authors.initials: OP
authors.lastname: Smith
authors.forename: B
authors.initials: B
authors.lastname: White
authors.forename: D
authors.initials: D
authors.lastname: Vaughan
authors.forename: M
authors.initials: M
authors.lastname: Rafferty
authors.forename: L
authors.initials: L
authors.lastname: Claffey
authors.forename: B
authors.initials: B
authors.lastname: Lyons
authors.forename: W
authors.initials: W
authors.lastname: Casey
mesh_terms: D000293:Adolescent; D000328:Adult; D000925:Anticoagulants / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D005260:Female; D017583:Hemodiafiltration; D006493:Heparin / Q000627:therapeutic use*; D006801:Humans; D011695:IgA Vasculitis / Q000209:etiology / Q000628:therapy*; D008297:Male; D008585:Meningitis, Meningococcal / Q000150:complications / Q000628:therapy*; D011379:Prognosis; D011486:Protein C / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D000925:Anticoagulants; D011486:Protein C; D006493:Heparin