Skip to main content
Top
Published in: Thrombosis Journal 1/2009

Open Access 01-12-2009 | Original clinical investigation

Plasma fibrinolysis is related to the degree of organ dysfunction but not to the concentration of von Willebrand Factor in critically ill patients

Authors: Karim Zouaoui Boudjeltia, Sandra Ollieuz, Michael Piagnerelli, Patrick Biston, Philippe Cauchie, Jean-Louis Vincent, Dany Brohee, Michel Vanhaeverbeek

Published in: Thrombosis Journal | Issue 1/2009

Login to get access

Abstract

Background

Endothelial cell dysfunction, by promoting fibrin deposition, has been implicated in the development of multiple organ failure. Altered fibrinolysis during inflammation may participate in microvascular alterations. We sought to determine whether plasma fibrinolysis was related to the severity of organ dysfunction and/or to the levels of von Willebrand factor (vWF antigen), as a marker of endothelium dysfunction, in critically ill patients.

Methods

Forty-nine consecutive patients admitted to an adult medico-surgical intensive care unit (ICU) with (18) or without sepsis (31) were included. C-reactive protein and vWF levels were measured on ICU admission and plasma fibrinolysis was assessed by the Euglobulin Clot Lysis Time (ECLT). The sequential organ failure assessment (SOFA) score and the simplified acute physiology score (SAPS) II were calculated on admission.

Results

ECLT was significantly longer in septic than in non-septic patients [1033 min (871–1372) versus 665 min (551–862), p = 0.001]. There were significant correlations between ECLT and C-reactive protein (CRP) concentrations (r = 0.78, p < 0.001) and the Sequential Organ Failure Assessment (SOFA) score (r = 0.39, p = 0.006). The level of vWF was not correlated with the ECLT (r = -0.06, p = 0.65) or the SOFA score (r = -0.02, p = 0.88).

Conclusion

ECLT measurement at admission could be a marker of organ dysfunction and a prognostic indicator in critically ill patients.
Appendix
Available only for authorised users
Literature
1.
go back to reference Aird WC: The role of the endothelium in severe sepsis and multiple organ dysfunction syndrome. Blood 2003, 101: 3765-3777. 10.1182/blood-2002-06-1887CrossRefPubMed Aird WC: The role of the endothelium in severe sepsis and multiple organ dysfunction syndrome. Blood 2003, 101: 3765-3777. 10.1182/blood-2002-06-1887CrossRefPubMed
2.
go back to reference Idell S: Coagulation, fibrinolysis, and fibrin deposition in acute lung injury. Crit Care Med 2003, 31: S213-S220. 10.1097/01.CCM.0000057846.21303.ABCrossRefPubMed Idell S: Coagulation, fibrinolysis, and fibrin deposition in acute lung injury. Crit Care Med 2003, 31: S213-S220. 10.1097/01.CCM.0000057846.21303.ABCrossRefPubMed
3.
go back to reference Lobo SM, Lobo FR, Bota DP, Lopes-Ferreira F, Soliman HM, Melot C, Vincent JL: C-reactive protein levels correlate with mortality and organ failure in critically ill patients. Chest 2003, 123: 2043-2049. 10.1378/chest.123.6.2043CrossRefPubMed Lobo SM, Lobo FR, Bota DP, Lopes-Ferreira F, Soliman HM, Melot C, Vincent JL: C-reactive protein levels correlate with mortality and organ failure in critically ill patients. Chest 2003, 123: 2043-2049. 10.1378/chest.123.6.2043CrossRefPubMed
4.
go back to reference Devaraj S, Xu DY, Jialal I: C-reactive protein increases plasminogen activator inhibitor-1 expression and activity in human aortic endothelial cells: implications for the metabolic syndrome and atherothrombosis. Circulation 2003, 107: 398-404. 10.1161/01.CIR.0000052617.91920.FDCrossRefPubMed Devaraj S, Xu DY, Jialal I: C-reactive protein increases plasminogen activator inhibitor-1 expression and activity in human aortic endothelial cells: implications for the metabolic syndrome and atherothrombosis. Circulation 2003, 107: 398-404. 10.1161/01.CIR.0000052617.91920.FDCrossRefPubMed
5.
go back to reference Bisoendial RJ, Kasteleuin JJ, Levels JHM, Zwaginga JJ, Bogaard B, Reitsma PH, Meijers CM, Hartman D, Levi M, Stroes ESG: Activation of inflammation and Coagulation after infusion of C-reactive protein in humans. Circ Res 2005, 96: 714-716. 10.1161/01.RES.0000163015.67711.ABCrossRefPubMed Bisoendial RJ, Kasteleuin JJ, Levels JHM, Zwaginga JJ, Bogaard B, Reitsma PH, Meijers CM, Hartman D, Levi M, Stroes ESG: Activation of inflammation and Coagulation after infusion of C-reactive protein in humans. Circ Res 2005, 96: 714-716. 10.1161/01.RES.0000163015.67711.ABCrossRefPubMed
6.
go back to reference Zouaoui Boudjeltia K, Piagnerelli M, Brohee D, Guillaume M, Cauchie P, Vincent JL, Remacle C, Boukaert Y, Vanhaeverbeek M: Relationship between CRP and hypofibrinolysis: is this a possible mechanism to explain the association between CRP and outcome in critically ill patients? Thromb J 2004, 2: 7. 10.1186/1477-9560-2-7PubMedCentralCrossRefPubMed Zouaoui Boudjeltia K, Piagnerelli M, Brohee D, Guillaume M, Cauchie P, Vincent JL, Remacle C, Boukaert Y, Vanhaeverbeek M: Relationship between CRP and hypofibrinolysis: is this a possible mechanism to explain the association between CRP and outcome in critically ill patients? Thromb J 2004, 2: 7. 10.1186/1477-9560-2-7PubMedCentralCrossRefPubMed
7.
go back to reference Blann AD: Plasma von Willebrand factor, thrombosis and the endothelium:the first 30 years. Thromb Haemost 2006, 95: 49-55.PubMed Blann AD: Plasma von Willebrand factor, thrombosis and the endothelium:the first 30 years. Thromb Haemost 2006, 95: 49-55.PubMed
8.
go back to reference Vincent JL, Moreno R, Takala J, Willatts S, De Mendonca A, Bruining H, Reinhart CK, Suter PM, Thijs LG: The SOFA (Sepsis-related Organ Failure Assessment) score to describe organ dysfunction/failure. On behalf of the Working Group on Sepsis-Related Problems of the European Society of Intensive Care Medicine. Intensive Care Med 1996, 22: 707-10. 10.1007/BF01709751CrossRefPubMed Vincent JL, Moreno R, Takala J, Willatts S, De Mendonca A, Bruining H, Reinhart CK, Suter PM, Thijs LG: The SOFA (Sepsis-related Organ Failure Assessment) score to describe organ dysfunction/failure. On behalf of the Working Group on Sepsis-Related Problems of the European Society of Intensive Care Medicine. Intensive Care Med 1996, 22: 707-10. 10.1007/BF01709751CrossRefPubMed
9.
go back to reference Le Gall JR, Lemeshow S, Saulnier F: A new Simplified Acute Physiology Score (SAPS II) based on a European/North American multicenter study. JAMA 1993, 270: 2957-2963. 10.1001/jama.270.24.2957CrossRefPubMed Le Gall JR, Lemeshow S, Saulnier F: A new Simplified Acute Physiology Score (SAPS II) based on a European/North American multicenter study. JAMA 1993, 270: 2957-2963. 10.1001/jama.270.24.2957CrossRefPubMed
10.
go back to reference Levy MM, Fink MP, Marshall JC, Abraham E, Angus D, Cook D, Cohen J, Opal SM, Vincent JL, Ramsay G: SCCM/ESICM/ACCP/ATS/SIS international sepsis definitions conference. Crit Care Med 2003, 31: 1250-1256. 10.1097/01.CCM.0000050454.01978.3BCrossRefPubMed Levy MM, Fink MP, Marshall JC, Abraham E, Angus D, Cook D, Cohen J, Opal SM, Vincent JL, Ramsay G: SCCM/ESICM/ACCP/ATS/SIS international sepsis definitions conference. Crit Care Med 2003, 31: 1250-1256. 10.1097/01.CCM.0000050454.01978.3BCrossRefPubMed
11.
go back to reference Zouaoui Boudjeltia K, Cauchie P, Remacle C, Guillaume M, Brohee D, Hubert JL, Vanhaeverbeek M: A new device for measurement of fibrin clot lysis: application to the euglobulin clot lysis time. BMC Biotechnol 2002, 2: 8. 10.1186/1472-6750-2-8CrossRefPubMed Zouaoui Boudjeltia K, Cauchie P, Remacle C, Guillaume M, Brohee D, Hubert JL, Vanhaeverbeek M: A new device for measurement of fibrin clot lysis: application to the euglobulin clot lysis time. BMC Biotechnol 2002, 2: 8. 10.1186/1472-6750-2-8CrossRefPubMed
12.
go back to reference Okabayashi K, Wada H, Ohta S, Shiku H, Nobori T, Maruyama K: Hemostatic markers and the sepsis-related organ failure assessment score in patients with disseminated intravascular coagulation in an intensive care unit. Am J Hematol 2004, 76: 225-229. 10.1002/ajh.20089CrossRefPubMed Okabayashi K, Wada H, Ohta S, Shiku H, Nobori T, Maruyama K: Hemostatic markers and the sepsis-related organ failure assessment score in patients with disseminated intravascular coagulation in an intensive care unit. Am J Hematol 2004, 76: 225-229. 10.1002/ajh.20089CrossRefPubMed
13.
go back to reference Kinasewitz GT, Yan SB, Basson B, Comp P, Russell JA, Cariou A, Um SL, Utterback B, Laterre PF, Dhainaut JF, PROWESS Sepsis Study Group: Universal changes in biomarkers of coagulation and inflammation occur in patients with severe sepsis, regardless of causative micro-organism [ISRCTN74215569]. Crit Care 2004, 8: R82-90. 10.1186/cc2459PubMedCentralCrossRefPubMed Kinasewitz GT, Yan SB, Basson B, Comp P, Russell JA, Cariou A, Um SL, Utterback B, Laterre PF, Dhainaut JF, PROWESS Sepsis Study Group: Universal changes in biomarkers of coagulation and inflammation occur in patients with severe sepsis, regardless of causative micro-organism [ISRCTN74215569]. Crit Care 2004, 8: R82-90. 10.1186/cc2459PubMedCentralCrossRefPubMed
14.
go back to reference Dhainaut JF, Shorr AF, Macias WL, Kollef MJ, Levi M, Reinhart K, Nelson DR: Dynamic evolution of coagulopathy in the first day of severe sepsis: relationship with mortality and organ failure. Crit Care Med 2005, 33: 341-348. 10.1097/01.CCM.0000153520.31562.48CrossRefPubMed Dhainaut JF, Shorr AF, Macias WL, Kollef MJ, Levi M, Reinhart K, Nelson DR: Dynamic evolution of coagulopathy in the first day of severe sepsis: relationship with mortality and organ failure. Crit Care Med 2005, 33: 341-348. 10.1097/01.CCM.0000153520.31562.48CrossRefPubMed
15.
go back to reference Cheng B, Xie G, Yao S, Wu X, Guo Q, Gu M, Fang Q, Xu Q, Wang D, Jin Y, Yuan S, Wang J, Du Z, Sun Y, Fang X: Epidemiology of severe sepsis in critically ill surgical patients in ten university hospitals in China. Crit Care Med 2007, 35: 2538-2546. 10.1097/01.CCM.0000284492.30800.00CrossRefPubMed Cheng B, Xie G, Yao S, Wu X, Guo Q, Gu M, Fang Q, Xu Q, Wang D, Jin Y, Yuan S, Wang J, Du Z, Sun Y, Fang X: Epidemiology of severe sepsis in critically ill surgical patients in ten university hospitals in China. Crit Care Med 2007, 35: 2538-2546. 10.1097/01.CCM.0000284492.30800.00CrossRefPubMed
16.
go back to reference Rivera-Fernández R, Nap R, Vázquez-Mata G, Reis Miranda D: Analysis of physiologic alterations in intensive care unit patients and their relationship with mortality. J Crit Care 2007, 22: 120-128. 10.1016/j.jcrc.2006.09.005CrossRefPubMed Rivera-Fernández R, Nap R, Vázquez-Mata G, Reis Miranda D: Analysis of physiologic alterations in intensive care unit patients and their relationship with mortality. J Crit Care 2007, 22: 120-128. 10.1016/j.jcrc.2006.09.005CrossRefPubMed
17.
go back to reference Gross PL, Aird WC: The endothelium and thrombosis. Semin Thromb Hemost 2000, 26: 463-478. 10.1055/s-2000-13202CrossRefPubMed Gross PL, Aird WC: The endothelium and thrombosis. Semin Thromb Hemost 2000, 26: 463-478. 10.1055/s-2000-13202CrossRefPubMed
18.
go back to reference Tomiyama H, Kumura Y, Mitsuhashi H, Kinouchi T, Yoshida H, Kushiro T, Doba N: Relationship between endothelial function and fibrinolysis in early hypertension. Hypertension 1998, 31: 321-327.CrossRefPubMed Tomiyama H, Kumura Y, Mitsuhashi H, Kinouchi T, Yoshida H, Kushiro T, Doba N: Relationship between endothelial function and fibrinolysis in early hypertension. Hypertension 1998, 31: 321-327.CrossRefPubMed
19.
go back to reference Poderos P: Endothelial dysfunction in the pathogenesis of atherosclerosis. Int Angiol 2002, 21: 109-116. Poderos P: Endothelial dysfunction in the pathogenesis of atherosclerosis. Int Angiol 2002, 21: 109-116.
20.
go back to reference Cerinic MM, Valentini G, Sorano GG, D'angelo S, Cuomo G, Fenu L, Generini S, Cinotti S, Morfini M, Pignono A, Guiducci S, Del Rosso A, Kaflin R, Das D, Marongiu F: Blood coagulation, fibrinolysis and markers of endothelial dysfunction in systemic sclerosis. Semin Arthritis Rheum 2003, 32: 285-295. 10.1053/sarh.2002.50011CrossRefPubMed Cerinic MM, Valentini G, Sorano GG, D'angelo S, Cuomo G, Fenu L, Generini S, Cinotti S, Morfini M, Pignono A, Guiducci S, Del Rosso A, Kaflin R, Das D, Marongiu F: Blood coagulation, fibrinolysis and markers of endothelial dysfunction in systemic sclerosis. Semin Arthritis Rheum 2003, 32: 285-295. 10.1053/sarh.2002.50011CrossRefPubMed
21.
go back to reference Schleef RR, Bridwell CR: Biochemical changes in endothelial cell monolayers induced by fibrin deposition in vitro. Arteriosclerosis 1984, 4: 14-20.CrossRefPubMed Schleef RR, Bridwell CR: Biochemical changes in endothelial cell monolayers induced by fibrin deposition in vitro. Arteriosclerosis 1984, 4: 14-20.CrossRefPubMed
22.
go back to reference Weimar B, Delvos U: The mechanism of fibrin-induced disorganization of cultured human endothelial cell monolayers. Arteriosclerosis 1986, 6: 139-145.CrossRefPubMed Weimar B, Delvos U: The mechanism of fibrin-induced disorganization of cultured human endothelial cell monolayers. Arteriosclerosis 1986, 6: 139-145.CrossRefPubMed
23.
go back to reference Qi J, Kerutzer DL: Fibrin regulation of interleukin-8 gene expression in human vascular endothelial cells. Blood 1997, 90: 3595-3602.PubMed Qi J, Kerutzer DL: Fibrin regulation of interleukin-8 gene expression in human vascular endothelial cells. Blood 1997, 90: 3595-3602.PubMed
24.
go back to reference Mavrommatis AC, Theodoridis T, Economou M, Kotanidou A, El Ali M, Christopoulou-Kokkinou V, Zakynthinos SG: Activation of the fibrinolytic system and utilization of the coagulation inhibitors in sepsis: comparison with severe sepsis and septic shock. Intensive Care Med 2001, 27: 1853-1859. 10.1007/s00134-001-1139-8CrossRefPubMed Mavrommatis AC, Theodoridis T, Economou M, Kotanidou A, El Ali M, Christopoulou-Kokkinou V, Zakynthinos SG: Activation of the fibrinolytic system and utilization of the coagulation inhibitors in sepsis: comparison with severe sepsis and septic shock. Intensive Care Med 2001, 27: 1853-1859. 10.1007/s00134-001-1139-8CrossRefPubMed
25.
go back to reference van Genderen PJ, Prins FJ, Lucas IS, van de Moesdijk D, van Cliet H, van Strik R, Michiels JJ: Decreased half-life time of plasma von Willebrand factor collagen binding activity in essential thrombocythaemia: normalization after cytoreduction of the increased platelet count. Br J Haematol 1997, 99: 832-836. 10.1046/j.1365-2141.1997.4823285.xCrossRefPubMed van Genderen PJ, Prins FJ, Lucas IS, van de Moesdijk D, van Cliet H, van Strik R, Michiels JJ: Decreased half-life time of plasma von Willebrand factor collagen binding activity in essential thrombocythaemia: normalization after cytoreduction of the increased platelet count. Br J Haematol 1997, 99: 832-836. 10.1046/j.1365-2141.1997.4823285.xCrossRefPubMed
26.
go back to reference Zouaoui Boudjeltia K, Guillaume M, Henuzet C, Delree P, Cauchie P, Remacle C, Ducobu J, Vanhaeverbeek M, Brohee D: Fibrinolysis and cardiovascular risk factors: association with fibrinogen lipids, and monocyte count. Eur J Intern Med 2006, 17: 102-108. 10.1016/j.ejim.2005.11.002CrossRefPubMed Zouaoui Boudjeltia K, Guillaume M, Henuzet C, Delree P, Cauchie P, Remacle C, Ducobu J, Vanhaeverbeek M, Brohee D: Fibrinolysis and cardiovascular risk factors: association with fibrinogen lipids, and monocyte count. Eur J Intern Med 2006, 17: 102-108. 10.1016/j.ejim.2005.11.002CrossRefPubMed
27.
go back to reference Koj A, Gauldie J, Regoeczi E, Sauder DN, Sweeney GD: The acute-phase response of cultured rat hepatocytes. System characterization and the effect of human cytokines. Biochem J 1984, 224: 505-514.PubMedCentralCrossRefPubMed Koj A, Gauldie J, Regoeczi E, Sauder DN, Sweeney GD: The acute-phase response of cultured rat hepatocytes. System characterization and the effect of human cytokines. Biochem J 1984, 224: 505-514.PubMedCentralCrossRefPubMed
28.
go back to reference Seki T, Gelehrter TD: Interleukin-1 induction of type-1 plasminogen activator inhibitor (PAI-1) gene expression in the mouse hepatocyte line, AML 12. J Cell Physiol 1996, 168: 648-656. Publisher Full Text 10.1002/(SICI)1097-4652(199609)168:3<648::AID-JCP17>3.0.CO;2-VCrossRefPubMed Seki T, Gelehrter TD: Interleukin-1 induction of type-1 plasminogen activator inhibitor (PAI-1) gene expression in the mouse hepatocyte line, AML 12. J Cell Physiol 1996, 168: 648-656. Publisher Full Text 10.1002/(SICI)1097-4652(199609)168:3<648::AID-JCP17>3.0.CO;2-VCrossRefPubMed
29.
go back to reference Chong AY, Blann AD, Lip GYH: Assessment of endothelial damage and dysfunction observations in relation to heart failure. QJM. 2003, 96(4):253-267. 10.1093/qjmed/hcg037CrossRefPubMed Chong AY, Blann AD, Lip GYH: Assessment of endothelial damage and dysfunction observations in relation to heart failure. QJM. 2003, 96(4):253-267. 10.1093/qjmed/hcg037CrossRefPubMed
30.
go back to reference Reinhart K, Bayer O, Brunkhorst F, Meisner M: Markers of endothelial damage dysfunction and sepsi. Crit Care Med 2002, 30: S302-S312. 10.1097/00003246-200205001-00021CrossRefPubMed Reinhart K, Bayer O, Brunkhorst F, Meisner M: Markers of endothelial damage dysfunction and sepsi. Crit Care Med 2002, 30: S302-S312. 10.1097/00003246-200205001-00021CrossRefPubMed
31.
go back to reference Ware LB, Eisneir MD, Thompson BT, Parsons PE, Matthay MA: Significance of von Willebrand factor in septic and nonseptic patients with acute lung injury. Am J Respir Crit Care Med 2004, 170: 766-772. 10.1164/rccm.200310-1434OCCrossRefPubMed Ware LB, Eisneir MD, Thompson BT, Parsons PE, Matthay MA: Significance of von Willebrand factor in septic and nonseptic patients with acute lung injury. Am J Respir Crit Care Med 2004, 170: 766-772. 10.1164/rccm.200310-1434OCCrossRefPubMed
32.
go back to reference Kayal S, Jaïs JP, Aguini N, Chaudiere J, Labrousse J: Elevated circulating E-selectin, intercellular adhesion molecule-1 and von willebrand factor in patients with severe infection. Am J Respir Crit Care Med. 1998, 157(3 Pt 1):776-784.CrossRefPubMed Kayal S, Jaïs JP, Aguini N, Chaudiere J, Labrousse J: Elevated circulating E-selectin, intercellular adhesion molecule-1 and von willebrand factor in patients with severe infection. Am J Respir Crit Care Med. 1998, 157(3 Pt 1):776-784.CrossRefPubMed
Metadata
Title
Plasma fibrinolysis is related to the degree of organ dysfunction but not to the concentration of von Willebrand Factor in critically ill patients
Authors
Karim Zouaoui Boudjeltia
Sandra Ollieuz
Michael Piagnerelli
Patrick Biston
Philippe Cauchie
Jean-Louis Vincent
Dany Brohee
Michel Vanhaeverbeek
Publication date
01-12-2009
Publisher
BioMed Central
Published in
Thrombosis Journal / Issue 1/2009
Electronic ISSN: 1477-9560
DOI
https://doi.org/10.1186/1477-9560-7-10

Other articles of this Issue 1/2009

Thrombosis Journal 1/2009 Go to the issue
Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin
Prof. Florian Limbourg
Prof. Anoop Chauhan
Developed by: Springer Medicine
Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.