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Semin Thromb Hemost 2001; 27(6): 633-638
DOI: 10.1055/s-2001-18867
Copyright © 2001 by Thieme Medical Publishers, Inc., 333 Seventh Avenue, New York, NY 10001, USA. Tel.: +1(212) 584-4662

Fibrinolysis in Disseminated Intravascular Coagulation

C. Erik Hack
  • Central Laboratory of the Netherlands Red Cross Blood Transfusion Service, Laboratory for Experimental and Clinical Immunology, University of Amsterdam, and Department of Clinical Chemistry, Free University Hospital, Amsterdam, The Netherlands
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Publication History

Publication Date:
06 December 2001 (online)

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ABSTRACT

Studies in experimental models for sepsis, the most common cause of disseminated intravascular coagulation (DIC), have put forward the concept of a procoagulant state that is characterized by thrombin generation exceeding that of plasmin. Convincing evidence indicates that this imbalance between coagulation and fibrinolysis is due to increased levels of plasminogen activator inhibitor type 1 (PAI-1). Levels of this fibrinolysis inhibitor indeed correlate with outcome and severity of multiple organ failure in patients with sepsis, as well as in patients with DIC from other causes. Hence we suggest that PAI-1 constitutes an important target for therapy in patients with DIC.

KEYWORD

Fibrinolysis - sepsis - plasminogen activator inhibitor type 1 - PAI-1 - plasminogen activators - multiple organ failure syndrome - MOFS

REFERENCES

  • 1 Vervloet M G, Thijs L G, Hack C E. Derangements of coagulation and fibrinolysis in critically ill patients with sepsis and septic shock.  Semin Thromb Hemost . 1998;  24 33-44
    PubMedGoogle Scholar
  • 2 Thijs L G, de Boer P J, de Groot C M, Hack C E. Coagulation disorders in septic shock.  Intensive Care Med . 1993;  19(Suppl 1) S8-S15
    CrossrefPubMedGoogle Scholar
  • 3 Levi M, ten Cate H. Disseminated intravascular coagulation.  N Engl J Med . 1999;  341 586-592
    CrossrefPubMedGoogle Scholar
  • 4 Levi M, ten Cate H, van der Poll T, van Deventer J S. Pathogenesis of disseminated intravascular coagulation in sepsis.  JAMA . 1993;  270 975-979
    CrossrefPubMedGoogle Scholar
  • 5 Gando S, Nanzaki S, Kemmotsu O. Disseminated intravascular coagulation and sustained systemic inflammatory response syndrome predict organ dysfunctions after trauma: application of clinical decision analysis.  Ann Surg . 1999;  229 121-127
    CrossrefPubMedGoogle Scholar
  • 6 Inthorn D, Hoffmann J N, Hartl W H, Muhlbayer D, Jochum M. Antithrombin III supplementation in severe sepsis: beneficial effects on organ dysfunction.  Shock . 1997;  8 328-334
    PubMedGoogle Scholar
  • 7 Jansen P M, Boermeester M A, Fischer E. Contribution of interleukin-1 to activation of coagulation and fibrinolysis, neutrophil degranulation, and the release of secretory-type phospholipase A2 in sepsis: studies in nonhuman primates after interleukin-1 alpha administration and during lethal bacteremia.  Blood . 1995;  86 1027-1034
    PubMedGoogle Scholar
  • 8 van der Poll T, Jansen P M, Van Zee J K. Pretreatment with a 55-kDa tumor necrosis factor receptor-immunoglobulin fusion protein attenuates activation of coagulation, but not of fibrinolysis, during lethal bacteremia in baboons.  J Infect Dis . 1997;  176 296-299
    PubMedGoogle Scholar
  • 9 van der Poll T, Jansen P M, Van Zee J K. Tumor necrosis factor-alpha induces activation of coagulation and fibrinolysis in baboons through an exclusive effect on the p55 receptor.  Blood . 1996;  88 922-927
    PubMedGoogle Scholar
  • 10 Bevilacqua M P, Pober J S, Majeau G R. Recombinant tumor necrosis factor induces procoagulant activity in cultured human vascular endothelium: characterization and comparison with the actions of interleukin 1.  Proc Natl Acad Sci USA . 1986;  83 4533-4537
    CrossrefPubMedGoogle Scholar
  • 11 Pober J S, Bevilacqua M P, Mendrick D L. Two distinct monokines, interleukin 1 and tumor necrosis factor, each independently induce biosynthesis and transient expression of the same antigen on the surface of cultured human vascular endothelial cells.  J Immunol . 1986;  136 1680-1687
    PubMedGoogle Scholar
  • 12 Bevilacqua M P, Pober J S, Majeau G R, Cotran R S, Gimbrone M AJ. Interleukin 1 (IL-1) induces biosynthesis and cell surface expression of procoagulant activity in human vascular endothelial cells.  J Exp Med . 1984;  160 618-623
    CrossrefPubMedGoogle Scholar
  • 13 Holmes W E, Nelles L, Lijnen H R, Collen D. Primary structure of human alpha 2-antiplasmin, a serine protease inhibitor (serpin).  J Biol Chem . 1987;  262 1659-1664
    PubMedGoogle Scholar
  • 14 Harpel P C. Alpha2-plasmin inhibitor and alpha2-macroglobulin-plasmin complexes in plasma. Quantitation by an enzyme-linked differential antibody immunosorbent assay.  J Clin Invest . 1981;  68 46-55
    CrossrefPubMedGoogle Scholar
  • 15 Levi M, Roem D, Kamp A M. Assessment of the relative contribution of different protease inhibitors to the inhibition of plasmin in vivo.  Thromb Haemost . 1993;  69 141-146
    PubMedGoogle Scholar
  • 16 Levi M, de Boer P J, Roem D, ten Cate W J, Hack C E. Plasminogen activation in vivo upon intravenous infusion of DDAVP. Quantitative assessment of plasmin-alpha 2-antiplasmin complex with a novel monoclonal antibody based radioimmunoassay.  Thromb Haemost . 1992;  67 111-116
    PubMedGoogle Scholar
  • 17 Ginsburg D, Zeheb R, Yang A Y. cDNA cloning of human plasminogen activator-inhibitor from endothelial cells.  J Clin Invest . 1986;  78 1673-1680
    CrossrefPubMedGoogle Scholar
  • 18 Antalis T M, Clark M A, Barnes T. Cloning and expression of a cDNA coding for a human monocyte-derived plasminogen activator inhibitor.  Proc Natl Acad Sci USA . 1988;  85 985-989
    PubMedGoogle Scholar
  • 19 Robbie L A, Dummer S, Booth N A, Adey G D, Bennett B. Plasminogen activator inhibitor 2 and urokinase-type plasminogen activator in plasma and leukocytes in patients with severe sepsis.  Br J Haematol . 2000;  109 342-348
    CrossrefPubMedGoogle Scholar
  • 20 Levi M, Hack C E, de Boer P J. Contact system dependent fibrinolytic activity in vivo: observations in healthy subjects and factor XII deficient patients.  Agents Actions Suppl . 1992;  38 292-298
    PubMedGoogle Scholar
  • 21 Bertozzi P, Astedt B, Zenzius L. Depressed bronchoalveolar urokinase activity in patients with adult respiratory distress syndrome.  N Engl J Med . 1990;  322 890-897
    CrossrefPubMedGoogle Scholar
  • 22 Kummer J A, Abbink J J, de Boer P J. Analysis of intraarticular fibrinolytic pathways in patients with inflammatory and noninflammatory joint diseases.  Arthritis Rheum . 1992;  35 884-893
    PubMedGoogle Scholar
  • 23 Carmeliet P, Schoonjans L, Kieckens L. Physiological consequences of loss of plasminogen activator gene function in mice.  Nature . 1994;  368 419-424
    CrossrefPubMedGoogle Scholar
  • 24 Halbmayer W M, Mannhalter C, Feichtinger C, Rubi K, Fischer M. The prevalence of factor XII deficiency in 103 orally anticoagulated outpatients suffering from recurrent venous and/or arterial thromboembolism.  Thromb Haemost . 1992;  68 285-290
    PubMedGoogle Scholar
  • 25 Koster T, Rosendaal F R, Briet E, Vandenbroucke J P. John Hageman's factor and deep-vein thrombosis: Leiden Thrombophilia Study.  Br J Haematol . 1994;  87 422-424
    CrossrefPubMedGoogle Scholar
  • 26 Ichinose A, Fujikawa K, Suyama T. The activation of pro-urokinase by plasma kallikrein and its inactivation by thrombin.  J Biol Chem . 1986;  261 3486-3489
    PubMedGoogle Scholar
  • 27 Schousboe I, Feddersen K, Rojkjaer R. Factor XIIa is a kinetically favorable plasminogen activator.  Thromb Haemost . 1999;  82 1041-1046
    PubMedGoogle Scholar
  • 28 Braat E A, Dooijewaard G, Rijken D C. Fibrinolytic properties of activated FXII.  Eur J Biochem . 1999;  263 904-911
    CrossrefPubMedGoogle Scholar
  • 29 Suffredini A F, Harpel P C, Parrillo J E. Promotion and subsequent inhibition of plasminogen activation after administration of intravenous endotoxin to normal subjects [see comments].  N Engl J Med . 1989;  320 1165-1172
    CrossrefPubMedGoogle Scholar
  • 30 van Deventer J S, Büller H R, ten Cate W J. Experimental endotoxemia in humans: analysis of cytokine release and coagulation, fibrinolytic, and complement pathways.  Blood . 1990;  76 2520-2526
    CrossrefPubMedGoogle Scholar
  • 31 Mesters R M, Florke N, Ostermann H, Kienast J. Increase of plasminogen activator inhibitor levels predicts outcome of leukocytopenic patients with sepsis.  Thromb Haemost . 1996;  75 902-907
    Article in Thieme ConnectPubMedGoogle Scholar
  • 32 Pralong G, Calandra T, Glauser M P. Plasminogen activator inhibitor 1: a new prognostic marker in septic shock.  Thromb Haemost . 1989;  61 459-462
    PubMedGoogle Scholar
  • 33 van der Poll T, Levi M, Büller H R. Fibrinolytic response to tumor necrosis factor in healthy subjects.  J Exp Med . 1991;  174 729-732
    CrossrefPubMedGoogle Scholar
  • 34 Levi M, ten Cate H, Bauer K A. Inhibition of endotoxin-induced activation of coagulation and fibrinolysis by pentoxifylline or by a monoclonal anti-tissue factor antibody in chimpanzees.  J Clin Invest . 1994;  93 114-120
    CrossrefPubMedGoogle Scholar
  • 35 Biemond B J, Levi M, ten Cate H. Plasminogen activator and plasminogen activator inhibitor 1 release during experimental endotoxaemia in chimpanzees: Effect of interventions in the cytokine and coagulation cascades.  Clin Sci . 1995;  88 587-594
    CrossrefPubMedGoogle Scholar
  • 36 Biemond B J, Levi M, ten Cate H. Complete inhibition of endotoxin-induced coagulation activation in chimpanzees with a monoclonal Fab fragment against factor VII/VIIa.  Thromb Haemost . 1995;  73 223-230
    PubMedGoogle Scholar
  • 37 van der Poll T, Levi M, van Deventer J S. Differential effects of anti-tumor necrosis factor monoclonal antibodies on systemic inflammatory responses in experimental endotoxemia in chimpanzees.  Blood . 1994;  83 446-451
    PubMedGoogle Scholar
  • 38 de Boer P J, Creasy A A, Chang A. Activation patterns of coagulation and fibrinolysis in baboons following infusion with lethal or sublethal dose of Escherichia coli Circ Shock .  1993;  39 59-67
    PubMedGoogle Scholar
  • 39 Minnema M C, Chang A C, Jansen P M. Recombinant human antithrombin III improves survival and attenuates inflammatory responses in baboons lethally challenged with Escherichia coli Blood .  2000;  95 1117-1123
    PubMedGoogle Scholar
  • 40 Jansen P M, Pixley R A, Brouwer M. Inhibition of factor XII in septic baboons attenuates the activation of complement and fibrinolytic systems and reduces the release of interleukin-6 and neutrophil elastase.  Blood . 1996;  87 2337-2344
    PubMedGoogle Scholar
  • 41 Cugno M, Hack C E, de Boer P J. Generation of plasmin during acute attacks of hereditary angioedema.  J Lab Clin Med . 1993;  121 38-43
    PubMedGoogle Scholar
  • 42 van der Linden W P, Hack C E, Struyvenberg A. Controlled insect-sting challenge in 55 patients: Correlation between activation of plasminogen and the development of anaphylactic shock.  Blood . 1993;  82 1740-1748
    PubMedGoogle Scholar
  • 43 Agostoni A, Gardinali M, Frangi D. Activation of complement and kinin systems after thrombolytic therapy in patients with acute myocardial infarction. A comparison between streptokinase and recombinant tissue-type plasminogen activator.  Circulation . 1994;  90 2666-2670
    CrossrefPubMedGoogle Scholar
  • 44 Biemond B J, Levi M, Coronel R. Thrombolysis and reocclusion in experimental jugular vein and coronary artery thrombosis. Effects of a plasminogen activator inhibitor type 1-neutralizing monoclonal antibody.  Circulation . 1995;  91 1175-1181
    PubMedGoogle Scholar
  • 45 Friederich P W, Levi M, Biemond B J. Novel low-molecular-weight inhibitor of PAI-1 (XR5118) promotes endogenous fibrinolysis and reduces postthrombolysis thrombus growth in rabbits.  Circulation . 1997;  96 916-921
    PubMedGoogle Scholar
  • 46 de Fouw J N, de Jong F Y, Haverkate F, Bertina R M. Activated protein C increases fibrin clot lysis by neutralization of plasminogen activator inhibitor-no evidence for a cofactor role of protein S.  Thromb Haemost . 1988;  60 328-333
    PubMedGoogle Scholar
  • 47 Taylor F BJ, Chang A, Esmon C T. Protein C prevents the coagulopathic and lethal effects of Escherichia coli infusion in the baboon.  J Clin Invest . 1987;  79 918-925
    CrossrefPubMedGoogle Scholar
  • 48 Esmon C T. Introduction: Are natural anticoagulants candidates for modulating the inflammatory response to endotoxin?.  Blood . 2000;  95 1113-1116
    PubMedGoogle Scholar
  • 49 Kario K, Matsuo T, Kodama K. Imbalance between thrombin and plasmin activity in disseminated intravascular coagulation. Assessment by the thrombin-antithrombin-III complex/plasmin-alpha-2-antiplasmin complex ratio.  Haemostasis . 1992;  22 179-186
    PubMedGoogle Scholar
  • 50 Takahashi H, Tatewaki W, Wada K, Hanano M, Shibata A. Thrombin versus plasmin generation in disseminated intravascular coagulation associated with various underlying disorders [see comments].  Am J Hematol . 1990;  33 90-95
    PubMedGoogle Scholar
  • 51 Okamoto K, Takaki A, Takeda S, Katoh H, Ohsato K. Coagulopathy in disseminated intravascular coagulation due to abdominal sepsis: Determination of prothrombin fragment 1 + 2 and other markers.  Haemostasis . 1992;  22 17-24
    PubMedGoogle Scholar
  • 52 Asakura H, Jokaji H, Saito M. Study of the balance between coagulation and fibrinolysis in disseminated intravascular coagulation using molecular markers.  Blood Coagul Fibrinolysis . 1994;  5 829-832
    PubMedGoogle Scholar
  • 53 Niessen R W, Lamping R J, Jansen P M. Antithrombin acts as a negative acute phase protein as established with studies on HepG2 cells and in baboons.  Thromb Haemost . 1997;  78 1088-1092
    PubMedGoogle Scholar
  • 54 Brandtzaeg P, Joo G B, Brusletto B, Kierulf P. Plasminogen activator inhibitor 1 and 2, alpha-2-antiplasmin, plasminogen, and endotoxin levels in systemic meningococcal disease.  Thromb Res . 1990;  57 271-278
    CrossrefPubMedGoogle Scholar
  • 55 Brandtzaeg P, Joo G B, Brusletto B, Kierulf P. Plasminogen activator inhibitor 1 and 2, alpha-2-antiplasmin, plasminogen, and endotoxin levels in systemic meningococcal disease.  Thromb Res . 1990;  57 271-278
    CrossrefPubMedGoogle Scholar
  • 56 Gando S, Nakanishi Y, Tedo I. Cytokines and plasminogen activator inhibitor-1 in posttrauma disseminated intravascular coagulation: Relationship to multiple organ dysfunction syndrome.  Crit Care Med . 1995;  23 1835-1842
    CrossrefPubMedGoogle Scholar
  • 57 Voss R, Matthias F R, Borkowski G, Reitz D. Activation and inhibition of fibrinolysis in septic patients in an internal intensive care unit.  Br J Haematol . 1990;  75 99-105
    CrossrefPubMedGoogle Scholar
  • 58 Massignon D, Lepape A, Bienvenu J. Coagulation/fibrinolysis balance in septic shock related to cytokines and clinical state.  Haemostasis . 1994;  24 36-48
    PubMedGoogle Scholar
  • 59 Asakura H, Jokaji H, Saito M. Changes in plasma levels of tissue-plasminogen activator/inhibitor complex and active plasminogen activator inhibitor in patients with disseminated intravascular coagulation.  Am J Hematol . 1991;  36 176-183
    PubMedGoogle Scholar
  • 60 Nuijens J H, Huijbregts C C, Eerenberg-Belmer A J. Quantification of plasma factor XIIa-Cl-inhibitor and kallikrein-Cl-inhibitor complexes in sepsis.  Blood . 1988;  72 1841-1848
    PubMedGoogle Scholar
  • 61 Hermans P W, Hibberd M L, Booy R. 4G/5G promoter polymorphism in the plasminogen-activator-inhibitor-1 gene and outcome of meningococcal disease. Meningococcal Research Group.  Lancet . 1999;  354 556-560
    CrossrefPubMedGoogle Scholar
  • 62 Hack C E. Tissue factor pathway of coagulation in sepsis.  Crit Care Med . 2000;  28 S25-S30
    PubMedGoogle Scholar
  • 63 Taylor F BJ, Chang A C, Peer G T. DEGR-factor Xa blocks disseminated intravascular coagulation initiated by Escherichia coli without preventing shock or organ damage.  Blood . 1991;  78 364-368
    PubMedGoogle Scholar
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