title: Local activation of coagulation and inhibition of fibrinolysis in the lung during ventilator associated pneumonia.
abstract: BACKGROUND
  Fibrin deposition is a hallmark of pneumonia. To determine the kinetics of alterations in local coagulation and fibrinolysis in relation to ventilator associated pneumonia (VAP), a single centre prospective study of serial changes in pulmonary and systemic thrombin generation and fibrinolytic activity was conducted in patients at risk for VAP.
  
  
  METHODS
  Non-directed bronchial lavage (NBL) was performed on alternate days in patients expected to require mechanical ventilation for more than 5 days. A total of 28 patients were studied, nine of whom developed VAP.
  
  
  RESULTS
  In patients who developed VAP a significant increase in thrombin generation was observed in the airways, as reflected by a rise in the levels of thrombin-antithrombin complexes in NBL fluid accompanied by increases in soluble tissue factor and factor VIIa concentrations. The diagnosis of VAP was preceded by a decrease in fibrinolytic activity in NBL fluid. Indeed, before VAP was diagnosed clinically, plasminogen activator activity levels in NBL fluid gradually declined, which appeared to be caused by a sharp increase in NBL fluid levels of plasminogen activator inhibitor 1.
  
  
  CONCLUSIONS
  VAP is characterised by a shift in the local haemostatic balance to the procoagulant side, which precedes the clinical diagnosis of VAP.
authors.affiliation: Department of Intensive Care Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands. m.j.schultz@amc.uva.nl
authors.forename: M J
authors.initials: MJ
authors.lastname: Schultz
authors.forename: J
authors.initials: J
authors.lastname: Millo
authors.forename: M
authors.initials: M
authors.lastname: Levi
authors.forename: C E
authors.initials: CE
authors.lastname: Hack
authors.forename: G J
authors.initials: GJ
authors.lastname: Weverling
authors.forename: C S
authors.initials: CS
authors.lastname: Garrard
authors.forename: T
authors.initials: T
authors.lastname: van der Poll
mesh_terms: D001777:Blood Coagulation / Q000502:physiology*; D005260:Female; D005337:Fibrin / Q000037:antagonists & inhibitors*; D005342:Fibrinolysis / Q000502:physiology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011014:Pneumonia / Q000097:blood* / Q000209:etiology; D011446:Prospective Studies; D012121:Respiration, Artificial / Q000009:adverse effects*
chemical_list: D005337:Fibrin