title: Combined antithrombin and protein C supplementation in meningococcal purpura fulminans: a pharmacokinetic study.
abstract: OBJECTIVE
  To document in patients with meningococcal purpura fulminans (PF), the effects of a combined supplementation with antithrombin (AT) and protein C (PC) plasma concentrates and to estimate the pharmacokinetics and dose requirements of each inhibitor.
  
  
  METHODS
  Retrospective study of 15 patients. SETTING. One paediatric and one adult ICU in a university hospital.
  
  
  METHODS
  In addition to standard intensive care, all patients received a 100 IU/kg loading dose of AT and PC concentrates, followed by a continuous infusion (AT: 100-150 IU.kg.day; PC: 100 IU.kg.day in adults, and 400 IU/kg in infants).
  
  
  METHODS
  Clinical data, coagulation, and fibrinolysis parameters, AT and PC activities, and free protein S (PS) levels were sequentially measured. Restitution ratio, median increment after supplementation, and half-life of clearance from plasma were calculated for the two plasma substitutes. RESULTS. At admission, all patients had a severe decrease in AT, PC, and PS levels. The supplementation regimen induced a substantial increase in AT and PC activities, peaking at H18 and H48, respectively. The supplementation procedure did not modify free PS levels. The median values of AT and PC restitution ratio, increment in plasma activity observed after 100 IU/kg concentrate, and apparent half-life of clearance from plasma were 0.85 U.ml.U.kg and 0.59 U.ml.U.kg, 23% and 21%, 16 h and 6 h, respectively.
  
  
  CONCLUSIONS
  If AT and PC concentrates are to be given in fulminant meningococcemia, the doses of supplementation should be at least 150 IU/kg AT and 250 IU/kg PC as loading dose and 150 IU/kg AT and 200 IU/kg PC as daily maintenance therapy. Taking into account the individual variability in inhibitor deficiency and restitution ratio, repeated measurements of plasma levels are mandatory to obtain a patient-based adjustment of the supplementation.
authors.affiliation: Service de Réanimation, Polyvalente Hôpital Roger Salengro, CHRU, 59037, Lille, France. f-fourrier@chru-lille.fr
authors.forename: François
authors.initials: F
authors.lastname: Fourrier
authors.forename: Francis
authors.initials: F
authors.lastname: Leclerc
authors.forename: Karl
authors.initials: K
authors.lastname: Aidan
authors.forename: Ahmed
authors.initials: A
authors.lastname: Sadik
authors.forename: Mercé
authors.initials: M
authors.lastname: Jourdain
authors.forename: Antoine
authors.initials: A
authors.lastname: Tournoys
authors.forename: Odile
authors.initials: O
authors.lastname: Noizet
mesh_terms: D000991:Antithrombins / Q000008:administration & dosage / Q000493:pharmacokinetics*; D005602:France; D006801:Humans; D011695:IgA Vasculitis / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism; D008589:Meningococcal Infections / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism; D011486:Protein C / Q000008:administration & dosage / Q000493:pharmacokinetics*; D012189:Retrospective Studies; D016896:Treatment Outcome
chemical_list: D000991:Antithrombins; D011486:Protein C