Skip to main content
SpringerLink
Log in
Book cover

Pathophysiology of Shock, Sepsis, and Organ Failure pp 459–467Cite as

Activation of Humoral Systems: Coagulation, Fibrinolysis, and Plasma Kallikrein-Kinin Systems

  • Chapter

Abstract

Severe infections and sepsis are characterized by ac tivation of the humoral cascade systems, including coagulation, fibrinolysis, and the plasma kalli-krein-kinin systems [1–25]. Both experimental and clinical studies have suggested that these protease systems are involved in the development of such complications as adult respiratory distress syn drome (ARDS) [26–29] and multiple organ failure (MOF) [29–31]. Furthermore, release of proteases from circulating cells, such as granulocyte elastase, has also been suggested to be an important factor in developing endothelial cell damage, leading to extensive permeability changes in the various organs [32–35].

This is a preview of subscription content, log in via an institution.

Chapter
USD   29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD   129.00
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD   169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Learn about institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Hardaway RM (1962) The role of intramuscular clot ting in the etiology of shock. Ann Surg 155:325–338.

    Article  PubMed  CAS  Google Scholar 

  2. Rapaport SI, Tatter D, Coer-Barron N, Hjort PF (1964) Pseudomonas septicemia with intravascular clotting leading to the generalized Schwartzmann re action. N Engl J Med 271:80–84.

    Article  PubMed  CAS  Google Scholar 

  3. Mason JW, Kleeberg U, Dolan P, Colman RW (1970) Plasma kallikrein and Hageman factor in gram nega tive bacteremia. Ann Intern Med 73:545–551.

    PubMed  CAS  Google Scholar 

  4. Hirsch EF, Fletcher IR, Moquin R (1971) Coagula tion changes after combat trauma and sepsis. Surg Gynecol Obstet 133:393–398.

    PubMed  CAS  Google Scholar 

  5. Hirsch EF, Nakajima T, Ishima G, Erdös EG, Herman CM (1974) Kinin system responses in sepsis af ter trauma in man. J Surg Res 17:147–153.

    Article  PubMed  CAS  Google Scholar 

  6. Robinson JA, Klodnycky ML, Loeb HS, Racic MR, Gunnar RM (1975) Endotoxin, prekallikrein, com plement and systemic vascular resistance. Am J Med 59:61–67.

    Article  PubMed  CAS  Google Scholar 

  7. O’Donnell TF, Clowes GHA (1976) Kinin activation in the blood of patients with sepsis. Surg Gynecol Obstet 143:539–544.

    PubMed  Google Scholar 

  8. McConn R, Wassermann F, Haberland G (1982) The kallikrein-kinin system in the acutely ill: changes in plasma kininogen in acutely ill patients and the effi cacy of pulmonary clearance of bradykinin. In: McConn R (ed) Role of chemical mediators in the pathophysiology of acute illness and injury. Raven, New York, pp 111–126.

    Google Scholar 

  9. Aasen AO, Smith-Erichsen N, Gallimore MJ, Amundsen E (1980) Studies on the components of the plasma kallikrein-kinin systems in plasma sam ples from normal individuals and patients with sep tic shock. Adv Shock Res 4:1–10.

    PubMed  CAS  Google Scholar 

  10. Fritz H (1980) Proteinase inhibitors in severe inflam matory processes (septic shock and experimental and therapeutic aspects). Ciba Found Symp 75:351–379.

    CAS  Google Scholar 

  11. Gallimore MJ, Aasen AO, Smith-Erichsen N, Larsbraaten M, Lyngaas K, Amundsen E (1980) Plasminogen concentrations and functional activi ties and concentrations of plasmin inhibitors in plas ma samples from normal subjects and patients with septic shock. Thromb Res 18:601–608.

    Article  PubMed  CAS  Google Scholar 

  12. Schipper HG, Roos J, van der Meulen F, ten Cate JW (1981) Antithrombin III deficiency in surgical in tensive care patients. Thromb Res 21:73–80.

    Article  PubMed  CAS  Google Scholar 

  13. Büller HR, Bolwer, ten Cate J, Ross J, Kahlè LH, ten Cate JW (1982) Postoperative hemostatic profile in relation to gram-negative septicemia. Crit Care Med 10:311–315.

    Article  PubMed  Google Scholar 

  14. ten Cate JW (1982) Antithrombin III: clinical signif icance. Acta Chir Scand 509:101–105.

    Google Scholar 

  15. Witte J, Jochum M, Scherer R, Schramm W, Hochstrasser K, Fritz H (1982) Distribution of se lected plasma proteins in hyperdynamic septic shock. Intensive Care Med 8:215–222.

    Article  PubMed  CAS  Google Scholar 

  16. Aasen AO, Kierulf P, Vaage J (1983) Determination of components of the plasma proteolytic enzyme systems given information of prognostic value in pa tients with multiple trauma. Adv Med Biol 156B: 1037–1047.

    Google Scholar 

  17. Smith-Erichsen N, Aasen AO, Gallimore MJ, Amundsen E (1982) Studies of components of the coagulation systems in normal individuals and in septic shock patients. Circ Shock 9:491–497.

    PubMed  CAS  Google Scholar 

  18. Kalter ES, Timmermanns A, Bouma BN (1982) The kinin generating system during sepsis and bacterial shock. Agents Actions 9:638–644.

    Google Scholar 

  19. Aasen AO, Smith-Erichsen N, Amundsen E (1983) Plasma kallikrein-kinin system in septicemia. Arch Surg 118:343–346.

    Article  PubMed  CAS  Google Scholar 

  20. Fuhrer G, Gallimore MJ, Heller W, Hoffmeister H-E (1987) Inhibition of β-FXII in plasma of volunteers and polytraumatized patients. Prog Clin Biol Res 236B:77–85.

    PubMed  CAS  Google Scholar 

  21. Smith-Erichsen N, Aasen AO (1984) Evaluation of severity and prognosis in early stages of septicemia by means of chromogenic peptide substrate assays. Eur Surg Res 2:140–146.

    Article  Google Scholar 

  22. Jochum M, Duswald K-H, Neumann S, Witte J, Fritz H (1984) Proteinases and their inhibitors in septicemia — basic concepts and clinical implica tions. Adv Exp Med Biol 167:391–404.

    PubMed  CAS  Google Scholar 

  23. Lämmle B, Tran TH, Ritz R, Duckert F (1984) Plasma prekallikrein, FXII, antithrombin III, C1-inhibitor and α2-macroglobulin in critically ill pa tients with suspected disseminated intravascular co agulation (DIC). Am J Clin Pathol 82:396–404.

    PubMed  Google Scholar 

  24. Kalter ES, Daha MR, ten Cate JW, Verhoef J, Bouma BN (1985) Activation and inhibition of Hageman factor-dependent pathways and the com plement system in uncomplicated bacteremia and bacterial shock. J Infect Dis 151:1019–1027.

    Article  PubMed  CAS  Google Scholar 

  25. Carlin G, Saldeen T (1982) Studies on posttraumatic fibrinolysis inhibition by use of tissue plasminogen activator. Haemostasis 11[Suppl]:85.

    Google Scholar 

  26. Saldeen T (1976) The microembolism syndrome. Microvasc Res 11:227–259.

    Article  PubMed  CAS  Google Scholar 

  27. Malik AB, van der Zee H (1977) Thrombin induced pulmonary insufficiency. Thromb Res 11:497–506.

    Article  PubMed  CAS  Google Scholar 

  28. Schlag G, Dinges HP, Redl H (1987) Quantitative es timation of leukostasis in the posttraumatic lung — canine and human autopsy data. Prog Clin Biol Res 236A:43–45.

    PubMed  Google Scholar 

  29. Schlag G, Redl H (1989) Lung in shock — postraumatic lung failure (organ failure) — MOFS. Prog Clin Biol Res 308:3–16.

    PubMed  CAS  Google Scholar 

  30. Aasen AO, Smith-Erichsen N, Amundsen E (1986) Uncontrolled plasma proteolysis: a major threat to the septicemic patient. Resuscitation 14:33–42.

    Article  PubMed  CAS  Google Scholar 

  31. Aasen AO, Rishovd A-L, Stadaas JO (1989) Role of endotoxin and proteases in multiple organ failure (MOF). Prog Clin Biol Res 308:315–322.

    PubMed  CAS  Google Scholar 

  32. Egbring R, Schmidt W, Fuchs G, Havemann K (1977) Demonstration of granulocyte proteases in plasma of patients with acute leukemia and septice mia with coagulation defects. Blood 49:219–231.

    PubMed  CAS  Google Scholar 

  33. Aasen AO, Ohlsson K (1978) Release of granulocyte elastase in lethal canine endotoxin shock. Hoppe Seylers Z Physiol Chem 359:683–687.

    PubMed  CAS  Google Scholar 

  34. Duswald K-H, Jochum M, Schramm W, Fritz H (1985) Release of granulocytic elastase: an indicator of pathobiochemical alteration in septicemia after abdominal surgery. Surgery 98:892–899.

    PubMed  CAS  Google Scholar 

  35. Bachmann F (1987) Plasminogen activators. In: Colman RW, Hirsh J, Marder VJ, Salzmann EW (eds) Hemostasis and thrombosis. Basic principles and clinical practice, 2nd edn. Lippincott, Philadelphia.

    Google Scholar 

  36. Suffredini AF, Harpel PC, Parrillo JE (1989) Pro motion and subsequent inhibition of plasminogen activation after administration of intravenous endo toxin to normal subjects. N Engl J Med 320: 1165–1171.

    Article  PubMed  CAS  Google Scholar 

  37. Van Deventer SJH, Buller HR, ten Cate JW, Aarden LA, Hack CE, Sturk A (1990) Experimental endotoxemia in humans: analysis of cytokine release and coagulation, fibrinolytic, and complement path ways. Blood 76:2520–2526.

    PubMed  Google Scholar 

  38. Kaplan AP, Meier HL, Mandle R Jr (1976) The Hageman factor dependent pathways of coagula tion, fibrinolysis, and kinin generation. Semin Thromb Hemostas 3:1–26.

    CAS  Google Scholar 

  39. Cochrane CG, Müller-Eberhard HJ (1968) The deri vation of two distance anaphylatoxic activities from the third and fifth component of human comple ment. J Exp Med 127:371–386.

    Article  PubMed  CAS  Google Scholar 

  40. Colman RW (1984) Surface mediated defence reac tions. The plasma contact activations system. J Clin Invest 73:1249–1253.

    Article  PubMed  CAS  Google Scholar 

  41. Kluft C, Dooijewaard G, Emeis JJ (1987) Role of the contact system in fibrinolysis. Semin Thromb Hemost 13:50–68.

    Article  PubMed  CAS  Google Scholar 

  42. Colman RW, Schmaier AH (1986) The contact acti vation system: biochemistry and interactions of these surface-mediated defense reactions. CRC Crit Rev Oncol Hematol 5:57–85.

    Article  CAS  Google Scholar 

  43. Erdös EG (1976) Commentary. The kinins. A status report. Biochem Pharmacol 25:1563–1569.

    Article  PubMed  Google Scholar 

  44. Kato H, Nagasawa S, Iwanaga S (1981) HMW and LMW kininogens. Methods Enzymol 80:172–198.

    Article  PubMed  CAS  Google Scholar 

  45. Robbins KC (1987) The plasminogen-plasmin en zyme system. In: Colman RW, Hirsh J, Marder VJ, Salzmann EW (eds) Hemostasis and thrombosis. Ba sic principles and clinical practice, 2nd edn. Lippin cott, Philadelphia.

    Google Scholar 

  46. Binnema DJ, Dooijewaard G, van Iersel JJL, Turion PNC, Kluft C (1990) The contact-system dependent plasminogen activator from human plasma: identifi-cation and characterization. Thromb Haemost 64(3):390–397.

    PubMed  CAS  Google Scholar 

  47. Nöss F, Røise O, Stadaas JO, Aasen AO (1989) The hemodynamic and proteolytic consequences of in travenous infusion of purified human plasma kalli krein. Thromb Haemostas 62:64.

    Google Scholar 

  48. Ward PA (1967) A plasmin split fragment of C 3 as a new chemotactic factor. J Exp Med 126:189–206.

    Article  PubMed  CAS  Google Scholar 

  49. Prydz H, Allison AC, Schorlemmer H-U (1977) Fur ther link between complement activation and blood coagulation. Nature 270:173–174.

    Article  PubMed  CAS  Google Scholar 

  50. Rivers RPA, Hathaway WE, Weston WL (1975) The endotoxin-induced coagulant activity of human monocytes. Cr J Haematol 30:311–316.

    Article  CAS  Google Scholar 

  51. Ratnoff OD, Pensky J, Ogston D, Naff GB (1969) The inhibition of plasmin, plasma kallikrein, plasma permeability factor, and the C1r subcomponent of the first component of complement by serum C-1 esterase inhibitor. J Exp Med 129:315–321.

    Article  PubMed  CAS  Google Scholar 

  52. Schapira M, Scott CF, Colman RW (1982) Contribu tion of plasma protease inhibitors to the inactivation of kallikrein in plasma. J Clin Invest 69:462–467.

    Article  PubMed  CAS  Google Scholar 

  53. Van der Graaf F, Koedam JA, Bouma BN (1983) In activation of kallikrein in human plasma. J Clin In vest 71:149–154.

    Article  Google Scholar 

  54. Schapira M (1987) Major inhibitors of the contact phase coagulation factors. Semin Thromb Hemost 13:69–78.

    Article  PubMed  CAS  Google Scholar 

  55. High KA (1988) Antithrombin III, protein C, and protein S. Naturally occurring anticoagulant pro teins. Arch Pathol Lab Med 112:28–36.

    PubMed  CAS  Google Scholar 

  56. Sandset PM, Abildgaard U, Pettersen M (1987) A sensitive assay of extrinsic coagulation pathway in hibitor (EPI) in plasma and plasma fractions. Thromb Res 47:389–400.

    Article  PubMed  CAS  Google Scholar 

  57. østerud B, Bjørklid E (1982) The production and availability of tissue thromboplastin in cellular pop ulations of whole blood exposed to various concen trations of endotoxin. An assay for detection of en dotoxin. Scand J Haematol 29:175–184.

    Article  PubMed  Google Scholar 

  58. Andersen OK, østerud B, Gaudernack G, Lundgren T-J, Giercksky K-E (1985) Tissue thromboplastin generation in circulating mononuclear phagocytes and development of coagulation disorders during E. coli endotoxemia in pigs. Acta Chir Scand 151: 205–211.

    PubMed  CAS  Google Scholar 

  59. Müller-Berghaus G, Hasegawa H (1983) Pathogene sis of disseminated intravascular coagulation. Bibl Haematol 49:3–13.

    PubMed  Google Scholar 

  60. Aasen AO, Dale J, Ohlsson K, Gallimore M (1978) Effects of slow intravenous administration of en dotoxin on blood cells and coagulation in dogs. Eur Surg Res 10:194–205.

    Article  PubMed  CAS  Google Scholar 

  61. Aasen AO, Frølich W, Saugstad OD, Amundsen E (1978) Plasma kallikrein activity and prekallikrein levels during endotoxin shock in dogs. Eur Surg Res 10:50–62.

    Article  PubMed  CAS  Google Scholar 

  62. Gallimore MJ, Aasen AO, Lyngaas KHN, Larsbraaten M, Amundsen E (1978) Falls in plasma levels of prekallikrein, high molecular weight kininogen and kallikrein inhibitors during lethal endotoxin shock in dogs. Thromb Res 12:307–318.

    Article  PubMed  CAS  Google Scholar 

  63. Aasen AO, Ohlsson K, Larsbraaten M, Amundsen E (1978) Changes in plasminogen levels, plasmin activity and activity of antiplasmin during endotoxin shock in dogs. Eur Surg Res 10:63–72.

    Article  PubMed  CAS  Google Scholar 

  64. Hesselvik JF, Blombäck M, Brodin B, Maller R (1989) Coagulation, fibrinolysis, and kallikrein sys tems in sepsis: relation to outcome. Crit Care Med 17:724–733.

    Article  PubMed  CAS  Google Scholar 

  65. Voss R, Matthias FR, Borkowski G, Reitz D (1990) Activation and inhibition of fibrinolysis in septic pa tients in an internal intensive care unit. Br J Haematol 75:99–105.

    Article  PubMed  CAS  Google Scholar 

  66. Brandtzaeg P, Sandset PM, Joø GB, øvstebø R, Abildgaard U, Kierulf P (1989) The quantitative as sociation of plasma endotoxin, antithrombin, pro tein C, extrinsic pathway inhibitor and fibrinopeptide A in systemic meningococcal disease. Thromb Res 55:459–470.

    Article  PubMed  CAS  Google Scholar 

  67. Gralnick HR, McKeown LR, Wilson OM, Williams SB, Elin RJ (1989) von Willebrand factor release in duced by endotoxin. J Lab Clin Med 113:118–122.

    PubMed  CAS  Google Scholar 

  68. Cooper NR, Morrison DC (1978) Binding and acti vation of the first component of human complement by the lipid A region of lipopolysaccharide. J Im munol 120:1862–1868.

    CAS  Google Scholar 

  69. Røise O, Bouma BN, Stadaas JO, Aasen AO (1988) Dose dependence of endotoxin induced activation of the plasma contact system: an in vitro study. Circ Shock 26:419–430.

    Google Scholar 

  70. Waeber G, Schapira M, Waeber B, Aubert JF, Nussberger J, Brunner HR (1988) Hypotensive effect of the active fragment derived from factor XII is me diated by an activation of the plasma kallikrein-kinin system. Circ Shock 26:375–382.

    PubMed  CAS  Google Scholar 

  71. Redl H, Schlag G, Paul E, Davies J (1989) Mono cyte/macrophage activation with cytokine release af ter polytrauma and sepsis in the baboon. Circ Shock 27:308.

    Google Scholar 

  72. Andreasson, Smith L, Aasen AO, Saldeen T, Risberg B (1988) Local pulmonary activitation of proteolytic enzymes after E. coli induced lung injury in sheep. Eur Surg Res 20:289–297.

    Article  PubMed  CAS  Google Scholar 

  73. Nuijens JH, Huijbregts CCM, Eerenberg AJM, Ab-bink JJ, Strack van Schijndel RJM, Felt-Bersma RJF, Thijs LG, Hack CE (1988) Quantification of plasma factor Xlla-Cl-inhibitor and kallikrein-C1-inhibitor complexes in sepsis. Blood 72:487–491.

    Google Scholar 

  74. Aasen AO (1985) The proenzyme functional inhibi tion index. A new parameter for the evaluation of the severely injured and septic patient. Acta Chir Scand [Suppl] 522:211–233.

    CAS  Google Scholar 

  75. Erdös EG, Sloane EM (1962) An enzyme in human blood plasma that inactivates bradykinin and kallidins. Biochem Pharmacol 11:585–592.

    Article  PubMed  Google Scholar 

  76. Røise O, Garred P, Mollnes TE, Aasen AO (1989) Studies on the dose dependence of endotoxin-in duced in vitro activation of the complement system. Eur Surg Res 21:34–41.

    Article  Google Scholar 

  77. Schlag G, Redl H, Hallström S (1991) The cell in shock: the origin of multiple organ failure. Resusci tation 21:137–180.

    Article  CAS  Google Scholar 

  78. Fritz H, Jochum M, Duswald K-H, Dittmer H, Kort-mann H, Neumann S, Lang H (1984) Granulocyte proteinases as mediators of unspecific proteolysis in inflammation. A review. In: Goldberg DM, Werner M (eds) Selected topics in clinical enzymology, vol. 2. De Gruyter, Berlin, pp 305–328.

    Google Scholar 

  79. Nuytinck JKS, Goris JA, Redl H, Schlag G, van Munster PJJ (1986) Posttraumatic complications and inflammatory mediators. Arch Surg 121: 886–890.

    Article  PubMed  CAS  Google Scholar 

  80. Redl H, Schlag G, Dinges HP, Buurman W, Rithlein R, Pober J, Cotran R (1990) Endothelial activation after polytrauma and sepsis in the baboon. Circ Shock 31:79.

    Google Scholar 

  81. Cotran RS (1987) New roles for the endothelium in inflammation and immunity. Am J Pathol 129: 407–413.

    PubMed  CAS  Google Scholar 

  82. Bizios R, Lai LC, Cooper JA, Del Vecchio PJ, Malik AB (1988) Thrombin induced adherence of neutro phils to cultured endothelial monolayers: increased endothelial adhesiveness. J Cell Physiol 134: 275–280.

    Article  PubMed  CAS  Google Scholar 

  83. Baggiolini M (1991) Neutrophils, interleukin 8, and relat ed chemotactic cytokines. In: Sies H, Flohe L, Zimmer G (eds) Molecular aspects of inflammation. Springer, Berlin Heidelberg New York, pp 25–32.

    Google Scholar 

  84. Burrows GE (1981) The effect of protease inhibitors on experimentally induced equine E. coli endotoxemia. Toxicon 19:189–192.

    Article  PubMed  CAS  Google Scholar 

  85. Winn R, Gleisner J, Maunder K, Harlan J, Hildebrant J (1986) Lung permeability and hemodynamics during endotoxemia: effect of aprotinin. J Surg Res 41:620–626.

    Article  PubMed  CAS  Google Scholar 

  86. Svartholm E, Haglund U, Ljungberg J, Hedner U (1989) Influence of aprotinin, a protease inhibitor, on porcine E. coli shock. Acta Chir Scand 155:7–13.

    PubMed  CAS  Google Scholar 

  87. Triantaphyllopoulos DC (1984) Effects of human antithrombin III on mortality and blood coagulation induced in rabbits by endotoxin. Thromb Haemostas 51:232–235.

    CAS  Google Scholar 

  88. Schapira M, Ramus M-A, Waeber B, Brunner HR, Jallet S, Carvallo D, Roitsch C, Courtney M (1987) Protection by recombinant α1-antitrypsin Ala358 Arg358 against arterial hypotension induced by factor XII fragment. J Clin Invest 80:582–585.

    Article  PubMed  CAS  Google Scholar 

  89. Colman RW, Flores DN, de la Cadena RA, Scott CF, Cousens L, Barr PJ, Hoffman IB, Kueppers F, Fisher D, Idell S, Pasarello J (1988) Recombinant α1-anti trypsin Pittsburgh attenuates experimental gramnegative septicemia. Am J Pathol 130:418–426.

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Institute for Surgical Research, Rikshospitalet, The National Hospital, University of Oslo, N-0027, Oslo, Norway

    A. O. Aasen & L. Buø

Authors
  1. A. O. Aasen
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. L. Buø
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Ludwig-Boltzmann Institute for Experimental and Clinical Traumatology, Donaueschingenstraße 13, A-1200, Vienna, Austria

    Günther Schlag M. D.  & Heinz Redl Ph. D.  & 

Rights and permissions

Reprints and permissions

Copyright information

© 1993 Springer-Verlag Berlin Heidelberg

About this chapter

Cite this chapter

Aasen, A.O., Buø, L. (1993). Activation of Humoral Systems: Coagulation, Fibrinolysis, and Plasma Kallikrein-Kinin Systems. In: Schlag, G., Redl, H. (eds) Pathophysiology of Shock, Sepsis, and Organ Failure. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-76736-4_34

Download citation

  • DOI: https://doi.org/10.1007/978-3-642-76736-4_34

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-642-76738-8

  • Online ISBN: 978-3-642-76736-4

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation