Thromb Haemost 1997; 77(06): 1090-1095
DOI: 10.1055/s-0038-1656118
Clinical Studies
Schattauer GmbH Stuttgart

Plasminogen: An Important Hemostatic Parameter in Septic Patients

Cristina Duboscq
1   The Dpto. de Química Biólogica. Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Argentina
,
Irene Quintana
1   The Dpto. de Química Biólogica. Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Argentina
,
Ethel Bassilotta
1   The Dpto. de Química Biólogica. Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Argentina
,
Gabriela E Bergonzelli
2   Dpto. Gastroenteroiogy Division, University Hospital, Lausanne, Switzerland
,
Pablo Porterie
1   The Dpto. de Química Biólogica. Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Argentina
,
Beatriz Sassetti
1   The Dpto. de Química Biólogica. Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Argentina
,
Ana S Haedo
1   The Dpto. de Química Biólogica. Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Argentina
,
Nestor Wainsztein
3   Department of Critical Care, Hospital Privado Güemes, Buenos Aires, Argentina
,
Egbert K O Kruithof
4   Division of Angiology and Hemostasis, University Hospital, Geneva, Switzerland
,
Lucía Kordich
1   The Dpto. de Química Biólogica. Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Argentina
› Author Affiliations
Further Information

Publication History

Received 30 July 1996

Accepted after resubmission 26 February 1997

Publication Date:
26 July 2018 (online)

Summary

Background: Previously we observed in some but not all septic patients a low plasma concentration of plasminogen. Objectives: To investigate prospectively whether plasma levels of plasminogen or the ratio of plasminogen to alpha-2-antiplasmin have a prognostic value for survival from sepsis and to study the variation of other hemostatic parameters during septicemia. Patients: The study population consisted of 45 consecutive patients with septicemia, 15 non-septic patients from the same intensive care unit and 30 healthy volunteers. Measurements and Main Results: Plasminogen concentrations were significantly lower (p <0.001) in plasma of septic patients (median 0,62 IU/ml range: 15-1,06) than in plasma of healthy controls (median 1.00 IU/ml, range: 0.75-1.10) or of non-septic intensive care patients (median 00 IU/ml, range: 0.82-1.08). Among the other parameters tested, plasminogen activator inhibitor (PAI-1) antigen concentration and PAI activity were similar in septic and non-septic intensive care patients, but higher than in healthy controls. Concentrations of elastase-alpha-1- protease inhibitor or of thrombin-antithrombin complexes were higher in septic patients than in non-septic intensive care patients or healthy controls. A degraded form of plasminogen of 38 kDa was detected by Western blot analysis in the plasma of septic patients, but not in plasma of non-septic intensive care patients or controls. Plasminogen alone or the ratio of plasminogen to antiplasmin were good markers for survival from septicemia. E.g. for plasminogen at a cut off of 0.65 IU/ml, sensitivity was 90.5% and specificity 66.7%, whereas for the ratio of plasminogen over antiplasmin at a cut off ratio of 0,65 IU/ml, sensitivity was 95.2% and specificity 70.8%. Conclusion: Plasminogen or the ratio of plasminogen to antiplasmin are sensitive markers for survival in patients with septicemia.

 
  • references

  • 1 Bone RC, Balk RA, Cerra FB, Dellinger RP, Fein AM, Knaus WA, Schein RM, Sibbad W. Definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis. The American College of Chest Physicians/Society of Critical Care Medicine Consensus Conference Committee. Chest 1992; 10: 1644-1655
  • 2 Bone RC. The pathogenesis of sepsis. Ann Intern Med 1991; 115: 457-469
  • 3 Coalson JJ. Pathology of sepsis, septic shock and multiple organ failure. In: Perspective on sepsis and septic shock. Sibbald WJ, Sprung C. (eds). Society of Critical Care Medicine Fullefon CA: 1986. pp 27-57
  • 4 Philippé J, Offner F, Declerck PJ, Leroux-Roels G, Vogelaers D, Basele G, Collen D. Fibrinolysis and coagulation in patients with infectious disease and sepsis. Thromb Haemost 1991; 65: 291-295
  • 5 Hesselvik FJ, Blombäck M, Brodin B, Mailer R. Coagulation, Fibrinolysis and Kallikrein systems in sepsis: Relation to outcome. Crit Care Med 1989; 17: 724-733
  • 6 Dofferhoff AS, Bom VJ, de Vries-HospersHG, Van IngenJ, Van De MeerJ, Hazenberg BP, Mulder PO, Weits J. Pattern of cytokines, plasma endotoxin, plasminogen activator inhibition and acute-phase proteins during the treatment of severe sepsis in human. Crit Care Med 1992; 20: 185-192
  • 7 Salgado A, Boveda JL, Monasterio J, Segura RM, Mourelle M, Gomez-Jimenez J, Peracaula R. Inflammatory mediators and their influence on haemostasis. Haemost 1994; 24: 132-138
  • 8 Silverman P, Goldsmith GH, Spitzer TR, Rehmus EH, Berger NA. Effect of tumor necrosis factor on the human fibrinolytic system. J Clinical Oncology 1990; 08: 468-475
  • 9 Hellgren M, Egberg N, Klund EJ. Blood Coagulation and fibrinolytic factors and their inhibitors in critically ill patients. Intens Care Med 1984; 10: 23-28
  • 10 Seitz R, Wolf M, Egbring R, Radtke KP, Leisenfeld A, Pittner P, Havemam K. Participation and interactions of neutrophil elastase in haemostatic disorders of patients with severe infections. Eur J Haematology 1987; 38: 231-240
  • 11 Plow EF. The major fibrinolytic proteases of human leukocytes. Biochim Biophys Acta 1980; 630: 47-56
  • 12 Moroz L. Miniplasminogen: A mechanism for leukocyte modulation of plasminogen activation by urokinase. Blood 1981; 103: 58-97
  • 13 Machovich R, Owen W. The elastase mediated pathway of fibrinolysis. Blood Coagulation and Fibrinolysis 1990; 01: 79-90
  • 14 Christensen U, Sottrup-Jensen L, Magnusson S, Petersen T, Clemmensen I. Enzymic properties of the neoplasmin -val 442 (miniplasmin). Biochim Biophy Acta 1979; 567: 472-481
  • 15 Kordich LC, Porterie VP, Lago O, Bergonzelli GE, Sassetti B, Sanchez AvalosJC. Mini-plasminogen like molecule in septic patients. Thromb Res 1987; 47: 553-560
  • 16 Molinas FC, Kordich LC, Porterie P, Lerner G, Maiztegui J. Plasminogen abnormalities in patients with Argentine hemorrhagic fever. Thromb Res 1987; 48: 713-720
  • 17 Deutsch DG, Mertz ET. Plasminogen: purification from human plasma by affinity chromatography. Science 1970; 170: 1095-1096
  • 18 Laemmli UK. Cleavage of structural proteins during assembly of the head of bacteriophage T4. Nature 1970; 227: 680-685
  • 19 Towbin H, Stochelim T, Gordon J. Electrophoretic transfer of proteins from polyacrilamide gels to nilrocelulose sheets: Procedure and some applications. Proc Natl Acad Sci USA 1979; 76: 4350-4354
  • 20 Zweig MH, Campbell G. Receiver-Operating Characteristic (ROC) plots: a fundamental evaluation tool in clinical medicine. Clin Chem 1993; 39: 561-577
  • 21 Pralong G, Calandra T, Glauser MP, Schellekens J, Verhoef J, Bachmann F, Kruithof EKO. Plasminogen activator inhibitor 1: a new prognostic marker in septic shock. Thromb Haemost 1989; 61: 459-462
  • 22 Maestries JC, Kruithof EKO, Marie-Paule GasconMP, Herodin F, Agay D, Ythier A. In vivo modulation of coagulation and fibrinolysis by recombinant glycosylated human interleukin 6 in baboons. Eur Cytokine Netw 1994; 05: 275-281
  • 23 Kluft C, Verheyen JH, Jie AFH, Rijken DC, Preston FE, Sue LingHM, Jespersen J, Aasen AO. The postoperative fibrinolytic shutdown: a rapidly reverting acute phase patterns for the fast-acting inhibitor of tissue-type plasminogen activator after trauma. Scand J Clin Lab Invest 1985; 45: 605-610
  • 24 Lorente JA, Garcia-Frade LJ, Landin M, de PabloR Torrado C, Renes E, Garcia AvelloA. Time course of hemostatic abnormalities in sepsis and its relation to outcome. Chest 1993; 103: 1536-1542
  • 25 Kruithof EKO, Calandra T, Pralong G, Heumann D, Gérain J, Baumgartner JD, Bachmann F, Glause MP. Evolution of plasminogen activator inhibitor type 1 in patients with septic shock – correlation with cytokine concentrations. Fibrinolysis 1993; 07: 117-121
  • 26 Massignon D, Lepape A, Bienvenu J, Barbier B, Boileau C, Coeur P. Coagulation/fibrinolysis balance in septic shock related to cytokines and clinical state. Haemostas 1994; 24: 36-48
  • 27 Philippe J, Dooijewaard G, Offner F, Turion P, Baele G, Leroux-Roels G. Granulocyte elastase, tumor necrosis factor-alpha and urokinase levels as prognostic markers in severe infection. Thromb Haemost 1992; 68: 19-23
  • 28 Nuijens JH, Abbink JJ, Wachtfogel YT, Colman RW, Eerenberg AJ, Dors D, Kamp AJ, Strack vanSchijndel RJ, Thijs LG, Hack CE. Plasma elastase alpha-1-antitrypsin and lactoferrin in sepsis: evidence for neutrophils as mediators in fatal sepsis. J Lab Clin Med 1992; 119: 159-168