T Fuchs-Buder, P de Moerloose, B Ricou, G Reber, C Vifian, L Nicod, JA Romand and PM Suter
Department of Anesthesiology, University Hospital of Geneva, Switzerland.

Intraalveolar fibrin deposition is a typical finding in acute lung injury and is not necessarily harmful. However, persistence of intraalveolar fibrin deposit may lead to hyaline membrane formation and subsequent alveolar fibrosis, a histologic hallmark of late stages of acute respiratory distress syndrome (ARDS). Thus, timing of the intraalveolar clotting disorder seems to be critical. To explore the time course of factors contributing to fibrin deposition and resolution, we sequentially analyzed procoagulant activity and fibrin degradation (by D dimer) in bronchoalveolar lavage (BAL) fluid of patients developing ARDS and those at risk for, but finally not developing, the syndrome. A total of 36 bronchoalveolar lavages were performed in 11 patients developing ARDS and 15 lavages in 10 patients at risk for but not developing this syndrome. All patients were admitted to the intensive care unit for the treatment of sepsis, trauma, or shock. In early phases of ARDS, the procoagulant activity (PCA) in BAL was significantly higher than in the patients at risk, 320 +/- 83 U (mean +/- SEM) versus 50 +/- 25 U, p < 0.05. A similar difference was noted in subacute stages (280 +/- 91 versus 46 +/- 16 U, p < 0.05). In early ARDS we observed higher levels of D dimer in BAL than in patients at risk: 1,841 +/- 827 versus 293 +/- 134 ng/ml, p < 0.05. Similarly, values of D dimer in the subacute phase were 2,776 +/- 836 versus 237 +/- 125 ng/ml, p < 0.05. In ARDS as well as in the at- risk group, D dimer in BAL fluid showed good correlation with the polymorphonuclear leukocyte count and with protein content of BAL. There was no correlation between plasma and BAL levels of D dimer. We conclude that in ARDS both the procoagulant pathway and the fibrin degradation are markedly activated compared with these in patients at risk but finally not developing this syndrome. These findings expand our understanding of intraalveolar coagulation abnormalities by providing evidence of increased fibrin breakdown in this syndrome.

This article has been cited by other articles:

				M. J Schultz and M. Levi Pulmonary coagulopathy: a potential therapeutic target in different forms of lung injury Thorax, July 1, 2007; 62(7): 563 - 564. [Full Text] [PDF]

				G. B. Allen, T. Leclair, M. Cloutier, J. Thompson-Figueroa, and J. H. T. Bates The response to recruitment worsens with progression of lung injury and fibrin accumulation in a mouse model of acid aspiration Am J Physiol Lung Cell Mol Physiol, June 1, 2007; 292(6): L1580 - L1589. [Abstract] [Full Text] [PDF]

				B. A. Simon, R. B. Easley, D. N. Grigoryev, S.-F. Ma, S. Q. Ye, T. Lavoie, R. M. Tuder, and J. G. N. Garcia Microarray analysis of regional cellular responses to local mechanical stress in acute lung injury Am J Physiol Lung Cell Mol Physiol, November 1, 2006; 291(5): L851 - L861. [Abstract] [Full Text] [PDF]

				A. Chan, K. Jayasuriya, L. Berry, M. Roth-Kleiner, M. Post, and J. Belik Volutrauma activates the clotting cascade in the newborn but not adult rat Am J Physiol Lung Cell Mol Physiol, April 1, 2006; 290(4): L754 - L760. [Abstract] [Full Text] [PDF]

				T. Nishiuma, T. H. Sisson, N. Subbotina, and R. H. Simon Localization of Plasminogen Activator Activity within Normal and Injured Lungs by In Situ Zymography Am. J. Respir. Cell Mol. Biol., November 1, 2004; 31(5): 552 - 558. [Abstract] [Full Text] [PDF]

				J. M. Querol-Ribelles, J. M. Tenias, E. Grau, J. M. Querol-Borras, J. L. Climent, E. Gomez, and I. Martinez Plasma d-Dimer Levels Correlate With Outcomes in Patients With Community-Acquired Pneumonia Chest, October 1, 2004; 126(4): 1087 - 1092. [Abstract] [Full Text] [PDF]

				L. B. Ware, X. Fang, and M. A. Matthay Protein C and thrombomodulin in human acute lung injury Am J Physiol Lung Cell Mol Physiol, September 1, 2003; 285(3): L514 - L521. [Abstract] [Full Text] [PDF]

				P. Prabhakaran, L. B. Ware, K. E. White, M. T. Cross, M. A. Matthay, and M. A. Olman Elevated levels of plasminogen activator inhibitor-1 in pulmonary edema fluid are associated with mortality in acute lung injury Am J Physiol Lung Cell Mol Physiol, July 1, 2003; 285(1): L20 - L28. [Abstract] [Full Text] [PDF]

				E. Abraham Coagulation Abnormalities in Acute Lung Injury and Sepsis Am. J. Respir. Cell Mol. Biol., April 1, 2000; 22(4): 401 - 404. [Full Text]

				A. GÜNTHER, P. MOSAVI, S. HEINEMANN, C. RUPPERT, H. MUTH, P. MARKART, F. GRIMMINGER, D. WALMRATH, B. TEMMESFELD-WOLLBRÜCK, and W. SEEGER 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., February 1, 2000; 161(2): 454 - 462. [Abstract] [Full Text]

				A. Elssner, G. Mazur, and C. Vogelmeier Inhibition of factor XIIIa-mediated incorporation of fibronectin into fibrin by pulmonary surfactant Am J Physiol Lung Cell Mol Physiol, April 1, 1999; 276(4): L625 - L630. [Abstract] [Full Text] [PDF]

				M. LEVI, T. van der POLL, H. ten CATE, B. KUIPERS, B. J. BIEMOND, H. M. JANSEN, and J. W. ten CATE Differential Effects of Anti-cytokine Treatment on Bronchoalveolar Hemostasis in Endotoxemic Chimpanzees Am. J. Respir. Crit. Care Med., July 1, 1998; 158(1): 92 - 98. [Abstract] [Full Text] [PDF]