Plasminogen Activator Inhibitor 1: A New Prognostic Marker in Septic Shock

Summary

The prognostic value of plasminogen activator inhibitor type 1 (PAI-1) in septic shock was investigated in 52 patients with septic shock. The patients had significantly elevated serum PAI-1 levels with respect to the control group (p = 0.002). In patients not having a rapidly fatal underlying disease, PAI-1 was significantly higher in patients dying within a week after onset of shock than in survivors (median PAI-1: 900 and 307 ng/ml, respectively; p = 0.001). The analysis of the distribution of PAI-1 levels permitted retrospectively to determine a threshold level of PAI-1 which had prognostic significance. Mortality was 71% in patients with serum PAI-1 above 550 ng/ml, whereas only two patients (6%) having a PAI-1 below 550 ng/ml died within a week.

Thus, in patients with septic shock, PAI-1 appears to have a strong predictive value as to mortality. This early marker may help the clinician in identifying a subgroup of patients particularly at risk.

Keywords

Plasminogen activator inhibitor type 1 - Septicemia - Septic shock

• References

• 1 McCabe WR, Jackson GG. Gram-negative bacteremia, I. Etiology and ecology. Arch Intern Med 1962; 110: 847-855
• 2 Kreger BE, Craven DE, McCabe WR. Gram-negative bacteremia, IV. Re-evaluation of clinical features and treatement in 612 Patients. Am J Med 1980; 68: 344-355
• 3 Ziegler EJ, McCutchan JA, Fierer J. et al Treatment of Gramnegative bacteremia and shock with human antiserum to mutant E. coli. N Engl J Med 1982; 307: 1225-1230
• 4 Parker MM, Parillo JE. Septic shock: hemodynamics and pathogenesis. J Am Med Assoc 1983; 250: 3324-3327
• 5 Shubin H, Weil MH. Bacterial shock. J Am Med Assoc 1976; 235: 421-424
• 6 Bone RC, Fisher CJ, Clemmer TP. et al A controlled clinical trial of high dose methylprednisolone in the treatment of severe sepsis and septic shock. N Engl J Med 1987; 317: 653-658
• 7 Smith-Erichsen N, Aasen AO, Gallimore MJ, Amundsen E. Studies of components of the coagulation systems in normal individuals and septic shock patients. Circ Shock 1982; 9: 491-497
• 8 Hellgren M, Egberg N, Eklund J. Blood coagulation and fibrinolytic factors and their inhibitors in critically ill patients. Intensive Care Med 1984; 10: 23-28
• 9 Bachmann F. Fibrinolysis In: Verstraete M, Vermylen J, Lijnen R, Arnout J. (eds) Thrombosis and Haemostasis 1987. University Press; Leuven: 1987. pp 227-265
• 10 Chmielewska J, Ranby M, Wiman B. Evidence for a rapid inhibitor to tissue plasminogen activator in plasma. Thromb Res 1983; 31: 427-436
• 11 Kruithof EK O, Tran-Thang C, Ransijn A, Bachmann F. Demonstration of a fast-acting inhibitor of plasminogen activators in human plasma. Blood 1984; 64: 907-913
• 12 Erickson LA, Ginsberg MH, Loskutoff DJ. Detection and partial characterization of an inhibitor of plasminogen activator in human platelets. J Clin Invest 1984; 74: 1465-1472
• 13 Kruithof EK O, Tran-Thang C, Bachmann F. Studies on the release of a plasminogen activator inhibitor by human platelets. Thromb Haemostas 1986; 55: 201-205
• 14 Kruithof EK O, Nicoloso G, Bachmann F. Plasminogen activator inhibitor 1 Development of a radioimmunoassay and observations on its plasma concentration during venous occlusion and after platelet aggregation. Blood 1987; 70: 1645-1653
• 15 Colucci M, Paramo JA, Collen D. Generation in plasma of a fastacting inhibitor of plasminogen activator in response to endotoxin stimulation. J Clin Invest 1985; 75: 818-824
• 16 Engebretsen LF, Kierulf P, Brandtzaeg P. Extreme plasminogen activator inhibitor and endotoxin values in patients with meningococcal disease. Thromb Res 1986; 42: 713-716
• 17 Calandra T, Glauser MP, Schellekens J. et al Treatment of Gramnegative septic shock with human E. coli J5 immunoglobulin G J Infect Dis 1988; 158: 312-319
• 18 Kruskal WH, Wallis WA. J Am Statist Assoc 1952; 583
• 19 Beutler B, Cerami A. Cachectin: more than a tumor necrosis factor. N Engl J Med 1987; 316: 379-385
• 20 Tracey KJ, Beutler B, Lowry SF. et al Shock and tissue injury induced by recombinant human cachectin. Science 1986; 234: 470-474
• 21 Waage A, Halstensen A, Espevik T. Association between tumour necrosis factor in serum and fatal outcome in patients with meningococcal disease. Lancet 1987; 1: 355-357
• 22 Beutler B, Milsark IW, Cerami AC. Passive immunization against cachectin/tumor necrosis factor protects mice from lethal effect of endotoxin. Science 1985; 229: 869-867
• 23 Tracey KJ, Fong Y, Hesse DG. et al Anti-cachectin/TNF monoclonal antibodies prevent septic shock during lethal bacteremia. Nature 1987; 330: 662-664
• 24 Dinarello CA, Cannon JG, Wolff SM. et al Tumor necrosis factor is an endogenous pyrogen and induces production of interleukin 1. J Exp Med 1986; 163: 1433-1450
• 25 Dubor F, Dosne AM, Chedid L. Effect of polymyxin B and colimycin on induction of plasminogen antiactivator by lipopolysaccharide in human endothelial cell culture. Infect Immunol 1986; 52: 725-729
• 26 Crutchley DJ, Conanan LB. Endotoxin induction of an inhibitor of plasminogen activator in bovine pulmonary artery endothelial cells. J Biol Chem 1986; 261: 154-159
• 27 Emeis JJ, Kooistra T. Interleukin 1 and lipopolysaccharide induce an inhibitor of tissue-type plasminogen activator in vivo and in cultured endothelial cells. J Exp Med 1986; 163: 1260-1266
• 28 Nachmann RL, Hajjar KA, Silverstein KL. et al Interleukin 1 induces endothelial cell synthesis of plasminogen activator inhibitor. J Exp Med 1986; 163: 1595-1600
• 29 Schleef RR, Bevilacqua MP, Sawdey M, Gimbrone MA, Loskutoff DJ. Cytokine activation of vascular endothelium. Effects on tissue-type plasminogen activator and type 1 plasminogen activator inhibitor J Biol Chem 1988; 263: 5797-5803
• 30 Van Hinsbergh VW M, Kooistra T, Van den Berg EA, Princen HM G, Fiers W, Emeis JJ. Tumor necrosis factor increases the production of plasminogen activator inhibitor in human endothelial cells in vitro and in rats in vivo. Blood 1988; 72: 1467-1473
• 31 Medcalf RL, Kruithof EK O, Schleuning WD. Plasminogen activator inhibitor 1 and 2 are tumor necrosis factor/cachectin responsive genes. J Exp Med 1988; 168: 751-759
• 32 Phillips LL, Margaretten W, McKay DG. Changes in the fibrinolytic enzyme system following intravascular coagulation induced by thrombin and endotoxin. Am J Obstet Gynecol 1968; 100: 319-326
• 33 Bergstein JM, Michael AF. Renal cortical fibrinolytic activity in the rabbit following one or two doses of endotoxin. Thromb Diathes Haemorrh 1973; 29: 27-32
• 34 Colucci M, Balconi G, Lorenzet R. et al Cultured human endothelial cells generate tissue factor in response to endotoxin. J Clin Invest 1983; 71: 1893-1896
• 35 Nawroth PP, Stern DM. Modulation of endothelial cell hemostatic properties by tumor necrosis factor. J Exp Med 1986; 163: 740-745
• 36 Bevilacqua MP, Pober JS, Majeau GR, Fiers W, Cotran RS, Gimbrone MA. Recombinant tumor necrosis factor induces procoagulant activity in cultivated vascular endothelium: characterization and comparison with the actions of interleukin 1. Proc Natl Acad Sci USA 1986; 83: 4533-4537
• 37 Krishnamurti C, Barr CF, Hassett MA, Young GD, Alving BM. Plasminogen activator inhibitor: a regulator of ancrod induced fibrin deposition in rabbits. Blood 1987; 69: 798-803
• 38 Shimomura K, Manda T, Mukumoto S, Kobayashi K, Nakano K, Mori J. Recombinant human tumor necrosis factor a: thrombus formation is a cause of anti-tumor activity. Int J Cancer 1988; 41: 243-247
• 39 Hamsten A, De Faire U, Walldius G. et al Plasminogen activator inhibitor in plasma: risk factor for recurrent myocardial infarction. Lancet 1987; 2 (04) 3-8
• 40 Nilsson IM, Ljungner H, Tengborn L. Two different mechanisms in patients with venous thrombosis and defective fibrinolysis: low concentration of plasminogen activator or increased concentration of plasminogen activator inhibitor. Br Med J 1985; 290: 1453-1456
• 41 Juhan-Vague I, Valadier J, Alessi MC. et al Deficient t-PA release and elevated PA-inhibitor levels in patients with spontaneous or recurrent deep venous thrombosis. Thromb Haemostas 1987; 57: 67-72