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Thorax 59:130-135 doi:10.1136/thorax.2003.013888
  • Assisted ventilation

Local activation of coagulation and inhibition of fibrinolysis in the lung during ventilator associated pneumonia

  1. M J Schultz1,2,
  2. J Millo3,
  3. M Levi4,
  4. C E Hack5,
  5. G J Weverling6,
  6. C S Garrard3,
  7. T van der Poll2,7
  1. 1Department of Intensive Care Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands
  2. 2Laboratory of Experimental Internal Medicine, Academic Medical Center, University of Amsterdam
  3. 3Intensive Therapy Unit, John Radcliffe Hospital, Oxford, UK
  4. 4Department of Internal Medicine, Academic Medical Center, University of Amsterdam
  5. 5Department of Pathophysiology of Plasma Proteins, Central Laboratory of the Netherlands Red Cross Blood Transfusion Service, Amsterdam, The Netherlands
  6. 6Clinical Epidemiology and Biostatistics, Academic Medical Center, University of Amsterdam
  7. 7Department of Infectious Diseases, Tropical Medicine and AIDS, Academic Medical Center, University of Amsterdam
  1. Correspondence to:
    Dr M J Schultz
    Academic Medical Center, University of Amsterdam, Department of Intensive Care Medicine, C3-329, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands; m.j.schultzamc.uva.nl
  • Received 26 July 2003
  • Accepted 6 August 2003

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.

Conclusion: VAP is characterised by a shift in the local haemostatic balance to the procoagulant side, which precedes the clinical diagnosis of VAP.

Footnotes

  • This study was funded in part by the Oxford Health Services Research Committee (research project number 593).