Document Detail

Combined antithrombin and protein C supplementation in meningococcal purpura fulminans: a pharmacokinetic study.
MedLine Citation:
PMID:  12761614     Owner:  NLM     Status:  MEDLINE    
PURPOSE: 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. DESIGN: Retrospective study of 15 patients. SETTING. One paediatric and one adult ICU in a university hospital. INTERVENTIONS: 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; PC: 100 in adults, and 400 IU/kg in infants). MEASUREMENTS: 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 and 0.59, 23% and 21%, 16 h and 6 h, respectively. CONCLUSION: 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.
François Fourrier; Francis Leclerc; Karl Aidan; Ahmed Sadik; Mercé Jourdain; Antoine Tournoys; Odile Noizet
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Publication Detail:
Type:  Journal Article     Date:  2003-05-22
Journal Detail:
Title:  Intensive care medicine     Volume:  29     ISSN:  0342-4642     ISO Abbreviation:  Intensive Care Med     Publication Date:  2003 Jul 
Date Detail:
Created Date:  2003-07-09     Completed Date:  2003-12-09     Revised Date:  2004-11-17    
Medline Journal Info:
Nlm Unique ID:  7704851     Medline TA:  Intensive Care Med     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1081-7     Citation Subset:  IM    
Service de Réanimation, Polyvalente Hôpital Roger Salengro, CHRU, 59037, Lille, France.
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MeSH Terms
Antithrombins / administration & dosage,  pharmacokinetics*
Meningococcal Infections / complications,  drug therapy*,  metabolism
Protein C / administration & dosage,  pharmacokinetics*
Purpura, Schoenlein-Henoch / drug therapy*,  etiology,  metabolism
Retrospective Studies
Treatment Outcome
Reg. No./Substance:
0/Antithrombins; 0/Protein C

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