title: Decreased protein C, protein S, and antithrombin levels are predictive of poor outcome in Gram-negative sepsis caused by Burkholderia pseudomallei.
abstract: BACKGROUND
  Acute septicemic melioidosis is associated with systemic release of endotoxin and the proinflammatory cytokines tumor necrosis factor (TNF)-alpha, interleukin-1, and interleukin-6. Excessive release of these cytokines may lead to endothelial injury, depletion of naturally occurring endothelial modulators, microvascular thrombosis, organ failure, and death.
  
  
  METHODS
  Plasma samples drawn at baseline and after initial antimicrobial therapy in 30 patients with suspected acute severe melioidosis were assayed for D-dimer levels, protein C and protein S antigen levels, and antithrombin functional activities.
  
  
  RESULTS
  Both baseline and continued deficiencies of protein C, protein S, and antithrombin were statistically associated with a poor outcome by logistic regression. Baseline D-dimer levels were significantly higher in fatal cases than survivors and correlated inversely with protein C and antithrombin, suggesting both increased fibrin deposition and fibrinolysis.
  
  
  CONCLUSIONS
  The inflammatory response to systemic Burkholderia pseudomallei infection leads to depletion of the natural endothelial modulators protein C, protein S, and antithrombin. Both baseline and continued deficiency of these endothelial modulators is predictive of poor outcome in melioidosis.
authors.affiliation: Division of Infectious Disease, Rhode Island Hospital, Gerry House 113, 593 Eddy Street, and Infectious Diseases and Microbiologic Divisions of Brown University School of Medicine, Providence, Rhode Island 02903, USA. slarosa@lifespan.org
authors.forename: Steven P
authors.initials: SP
authors.lastname: LaRosa
authors.forename: Steven M
authors.initials: SM
authors.lastname: Opal
authors.forename: Barbara
authors.initials: B
authors.lastname: Utterback
authors.forename: Sau Chi Betty
authors.initials: SC
authors.lastname: Yan
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Helterbrand
authors.forename: Andrew J H
authors.initials: AJ
authors.lastname: Simpson
authors.forename: Wipada
authors.initials: W
authors.lastname: Chaowagul
authors.forename: Nicholas J
authors.initials: NJ
authors.lastname: White
authors.forename: Charles J
authors.initials: CJ
authors.lastname: Fisher
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000627:therapeutic use; D000991:Antithrombins / Q000032:analysis; D015415:Biomarkers / Q000097:blood; D016957:Burkholderia pseudomallei; D002442:Ceftazidime / Q000008:administration & dosage / Q000627:therapeutic use; D016207:Cytokines / Q000097:blood; D018572:Disease-Free Survival; D005260:Female; D005338:Fibrin Fibrinogen Degradation Products / Q000032:analysis; D006801:Humans; D015378:Imipenem / Q000008:administration & dosage / Q000627:therapeutic use; D007275:Injections, Intravenous; D016015:Logistic Models; D008297:Male; D008554:Melioidosis / Q000175:diagnosis* / Q000188:drug therapy / Q000503:physiopathology; D008875:Middle Aged; D011486:Protein C / Q000032:analysis; D017293:Protein S / Q000032:analysis; D012189:Retrospective Studies; D018805:Sepsis / Q000175:diagnosis* / Q000188:drug therapy / Q000503:physiopathology; D013785:Thailand; D016896:Treatment Outcome
chemical_list: D000900:Anti-Bacterial Agents; D000991:Antithrombins; D015415:Biomarkers; D016207:Cytokines; D005338:Fibrin Fibrinogen Degradation Products; D011486:Protein C; D017293:Protein S; C036309:fibrin fragment D; D015378:Imipenem; D002442:Ceftazidime