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. 2004 Feb;59(2):130–135. doi: 10.1136/thorax.2003.013888

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

M Schultz 1, J Millo 1, M Levi 1, C Hack 1, G Weverling 1, C Garrard 1, T van der Poll 1
PMCID: PMC1746934  PMID: 14760153

Abstract

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.

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Selected References

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  1. A'Court C. H., Garrard C. S., Crook D., Bowler I., Conlon C., Peto T., Anderson E. Microbiological lung surveillance in mechanically ventilated patients, using non-directed bronchial lavage and quantitative culture. Q J Med. 1993 Oct;86(10):635–648. doi: 10.1093/qjmed/86.10.635. [DOI] [PubMed] [Google Scholar]
  2. Abraham E. Coagulation abnormalities in acute lung injury and sepsis. Am J Respir Cell Mol Biol. 2000 Apr;22(4):401–404. doi: 10.1165/ajrcmb.22.4.f184. [DOI] [PubMed] [Google Scholar]
  3. Bernard G. R., Vincent J. L., Laterre P. F., LaRosa S. P., Dhainaut J. F., Lopez-Rodriguez A., Steingrub J. S., Garber G. E., Helterbrand J. D., Ely E. W. Efficacy and safety of recombinant human activated protein C for severe sepsis. N Engl J Med. 2001 Mar 8;344(10):699–709. doi: 10.1056/NEJM200103083441001. [DOI] [PubMed] [Google Scholar]
  4. Bertozzi P., Astedt B., Zenzius L., Lynch K., LeMaire F., Zapol W., Chapman H. A., Jr Depressed bronchoalveolar urokinase activity in patients with adult respiratory distress syndrome. N Engl J Med. 1990 Mar 29;322(13):890–897. doi: 10.1056/NEJM199003293221304. [DOI] [PubMed] [Google Scholar]
  5. Binnema D. J., van Iersel J. J., Dooijewaard G. Quantitation of urokinase antigen in plasma and culture media by use of an ELISA. Thromb Res. 1986 Sep 1;43(5):569–577. doi: 10.1016/0049-3848(86)90077-0. [DOI] [PubMed] [Google Scholar]
  6. Friederich P. W., Levi M., Bauer K. A., Vlasuk G. P., Rote W. E., Breederveld D., Keller T., Spataro M., Barzegar S., Büller H. R. Ability of recombinant factor VIIa to generate thrombin during inhibition of tissue factor in human subjects. Circulation. 2001 May 29;103(21):2555–2559. doi: 10.1161/01.cir.103.21.2555. [DOI] [PubMed] [Google Scholar]
  7. Garrard C. S., A'Court C. D. The diagnosis of pneumonia in the critically ill. Chest. 1995 Aug;108(2 Suppl):17S–25S. doi: 10.1378/chest.108.2_supplement.17s. [DOI] [PubMed] [Google Scholar]
  8. Günther A., Mosavi P., Heinemann S., Ruppert C., Muth H., Markart P., Grimminger F., Walmrath D., Temmesfeld-Wollbrück B., Seeger W. Alveolar fibrin formation caused by enhanced procoagulant and depressed fibrinolytic capacities in severe pneumonia. Comparison with the acute respiratory distress syndrome. Am J Respir Crit Care Med. 2000 Feb;161(2 Pt 1):454–462. doi: 10.1164/ajrccm.161.2.9712038. [DOI] [PubMed] [Google Scholar]
  9. Levi M., Ten Cate H. Disseminated intravascular coagulation. N Engl J Med. 1999 Aug 19;341(8):586–592. doi: 10.1056/NEJM199908193410807. [DOI] [PubMed] [Google Scholar]
  10. McDonald J. A. The yin and yang of fibrin in the airways. N Engl J Med. 1990 Mar 29;322(13):929–931. doi: 10.1056/NEJM199003293221311. [DOI] [PubMed] [Google Scholar]
  11. Nakstad B., Lyberg T., Skjønsberg O. H., Boye N. P. Local activation of the coagulation and fibrinolysis systems in lung disease. Thromb Res. 1990 Mar 15;57(6):827–838. doi: 10.1016/0049-3848(90)90150-b. [DOI] [PubMed] [Google Scholar]
  12. Pugin J., Auckenthaler R., Mili N., Janssens J. P., Lew P. D., Suter P. M. Diagnosis of ventilator-associated pneumonia by bacteriologic analysis of bronchoscopic and nonbronchoscopic "blind" bronchoalveolar lavage fluid. Am Rev Respir Dis. 1991 May;143(5 Pt 1):1121–1129. doi: 10.1164/ajrccm/143.5_Pt_1.1121. [DOI] [PubMed] [Google Scholar]
  13. Rijneveld Anita W., Florquin Sandrine, Bresser Paul, Levi Marcel, De Waard Vivian, Lijnen Roger, Van Der Zee Jaring S., Speelman Peter, Carmeliet Peter, Van Der Poll Tom. Plasminogen activator inhibitor type-1 deficiency does not influence the outcome of murine pneumococcal pneumonia. Blood. 2003 Apr 17;102(3):934–939. doi: 10.1182/blood-2003-01-0227. [DOI] [PubMed] [Google Scholar]
  14. Seeger W., Elssner A., Günther A., Krämer H. J., Kalinowski H. O. Lung surfactant phospholipids associate with polymerizing fibrin: loss of surface activity. Am J Respir Cell Mol Biol. 1993 Aug;9(2):213–220. doi: 10.1165/ajrcmb/9.2.213. [DOI] [PubMed] [Google Scholar]
  15. Seeger W., Hübel J., Klapettek K., Pison U., Obertacke U., Joka T., Roka L. Procoagulant activity in bronchoalveolar lavage of severely traumatized patients--relation to the development of acute respiratory distress. Thromb Res. 1991 Jan 1;61(1):53–64. doi: 10.1016/0049-3848(91)90168-v. [DOI] [PubMed] [Google Scholar]
  16. Verheijen J. H., Mullaart E., Chang G. T., Kluft C., Wijngaards G. A simple, sensitive spectrophotometric assay for extrinsic (tissue-type) plasminogen activator applicable to measurements in plasma. Thromb Haemost. 1982 Dec 27;48(3):266–269. [PubMed] [Google Scholar]
  17. de Moerloose P., De Benedetti E., Nicod L., Vifian C., Reber G. Procoagulant activity in bronchoalveolar fluids: no relationship with tissue factor pathway inhibitor activity. Thromb Res. 1992 Mar 1;65(4-5):507–518. doi: 10.1016/0049-3848(92)90202-l. [DOI] [PubMed] [Google Scholar]
  18. van der Poll T., de Jonge E., Levi M. Regulatory role of cytokines in disseminated intravascular coagulation. Semin Thromb Hemost. 2001 Dec;27(6):639–651. doi: 10.1055/s-2001-18868. [DOI] [PubMed] [Google Scholar]

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