Advertisement

Therapie mit Proteinaseinhibitoren. Antithrombin III

  • D. Inthorn

Zusammenfassung

Das ausgedehnte Gewebetrauma, Schockereignisse und v.a. bakterielle Infektionen führen nach heutigem Kenntnisstand zur Aktivierung der humoralen Kaskadensysteme: Gerinnungs-/Fibrinolysesystem, Komplementsystem, Kalli-krein-/Kininsystem. Faktoren aus diesen Systemen sind in der Lage, das Sepsis-syndrom mit Organversagen direkt (durch unmittelbare Beeinträchtigung von Zell- und Organfunktionen) oder indirekt durch Aktivierung von Zellsystemen mit konsekutiver Liberierung von Entzündungsmediatoren zu beeinflussen. Dabei sind ganz offensichtlich nicht einzelne Komponenten, sondern vielmehr komplexe Interaktionen zahlreicher Faktoren maßgebend für die Auslösung und Manifestation des septischen Geschehens bis hin zum Organversagen (Abb. 7.1).

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

Literatur

  1. 1.
    Abbink JJ, Nuijens JH, Eerenberg AJM, Huijbregts CCM, van Schijndel RJMS, Thijs LG, Hack CE (1991) Quantification of functional and inactivated α2-macroglobulin in sepsis. Thromb Haemost 65: 32–39PubMedGoogle Scholar
  2. 2.
    Asakura H, Jokaji H, Saito M, Uotana C, Kumabashiri I, Morishita E, Yamazaki M Matsuda T (1991) Plasma levels of soluble thrombomodulin increase in cases of disseminatd intravascular coagulation with organ failure. Am J Hematol 38: 281–287PubMedCrossRefGoogle Scholar
  3. 3.
    Blauhut B, Kramar H, Vinazzer H, Bergmann H (1985) Substitution of antithrombin III in shock and DIC:A randomized study. Thromb Res 39: 81–89PubMedCrossRefGoogle Scholar
  4. 4.
    Bleeker WK, Agterberg J, Rigter G, Hack CE, Gool JV (1992) Protective effect of antithrombin III in acute experimental pancreatitis in rats. Dig Dis Sei 37: 280–285CrossRefGoogle Scholar
  5. 5.
    Brandtzaeg P, Sandset M, Joo GB, Ovstebo R, Abildgaard U, Kierulf P (1989) The quantitative association of plasma endotoxin, antithrombin, protein C, extrinsic pathway inhibitor and fîbrinopeptid A in systemic meningococcal disease. Thromb Res 55: 459–470PubMedCrossRefGoogle Scholar
  6. 6.
    Deventer SJH van, Büller HR, Cate JW ten, Aarden LA, Hack CE, Sturk A (1990) Experimental endotoxemia in humans: Analysis of cytokine release and coagulation, fibrinolytic, and complement pathway. Blood 76: 2520–2526PubMedGoogle Scholar
  7. 7.
    Emerson TE, Fournel MA, Redens TB, Taylor FB (1989) Efficacy of antithrombin III supplementation in animal models of fulminant Escherichia coli endotoxemia or bacteremia. Am J Med 87 [Suppl 38]: 27S–33SCrossRefGoogle Scholar
  8. 8.
    Esmon NL, Esmon CT (1988) Protein C and the endothelium. Semin Thromb Hemost 14:210–215PubMedCrossRefGoogle Scholar
  9. 9.
    Fenton II JW, Villanueva GB, Ofosu FA, Maraganore JM (1991) Thrombin inhibition by hirudin: how hirudin inhibits thrombin. Haemostasis 21 [Suppl 1]: 27–31PubMedGoogle Scholar
  10. 10.
    Fourrier F, Lestavel P, Chopin C, Marey A, Godemand J, Rime A, Mangalaboyi J (1990) Meningococcemia and purpura fulminans in adults: acute deficiencies of proteins C and S and early treatment with antithrombin III concentrates. Intensive Care Med 16:121–124PubMedCrossRefGoogle Scholar
  11. 11.
    Fourrier F, Chopin C, Goudemand J, Hendrycx S, Caron C, Rime A, Marey A, Lestavel P (1992) Septic shock, multiple organ failure, and disseminated intravascular coagulation. Compared patterns of antithrombin III, protein C, and protein S deficiencies. Chest 101: 816–823PubMedCrossRefGoogle Scholar
  12. 12.
    Fourrier F, Chopin C, Huart JJ, Runge I, Caron C, Goudemand J (1993) Double-blind, placebo-controlled trial of antithrombin III concentrates in septic shock with disseminated intravascular coagulation. Chest 104: 882–888PubMedCrossRefGoogle Scholar
  13. 13.
    Harper PL, Park LWG, Carrell W (1990) Antithrombin supplementation in intensive care patients. Intensive Care Med 16: A143 (Abstract)Google Scholar
  14. 14.
    Hesselvik JF, Blomback M, Brodin B, Maller R (1989) Coagulation, fibrinolysis, and kallikrein systems in sepsis: Relation to outcome. Crit Care Med 17: 724–733PubMedCrossRefGoogle Scholar
  15. 15.
    Hoffmann H, Siebeck M, Spannagl M, Weis M, Geiger R, Jochum M, Fritz H (1990) Effect of recombinant hirudin, a specific inhibitor of thrombin on endotoxin-induced intravascular coagulation and acute lung injury in pigs. Am Rev Respir Dis 142: 782–788PubMedCrossRefGoogle Scholar
  16. 16.
    Neuhof H, Seeger W, Wolf H, Hall J, Neumann C, Srampical B (1984) Acut increase in pulmonary vascular resistance induced by circulating fibrin monomers, mediated by pulmonary thromboxane A2 generation. Eur J Res Dis 64: 473–482Google Scholar
  17. 17.
    Nowak G, Markwardt F (1991) Hirudin in disseminated intravascular coagulation. Haemostasis 21 [Suppl 1]: 142–148PubMedGoogle Scholar
  18. 18.
    Philippe J, Offner F, Declerc PJ, Leroux-Roels G, Vogelaers D, Baele G, Collen D (1991) Fibrinolysis and coagulation in patients with infectious disease and sepsis. Thromb Haemost 65: 291–295PubMedGoogle Scholar
  19. 19.
    Reeve E (1980) Stady state relations between factors X, Xa, wll, antithrombin III andα2-macroglobulin in thrombosis. Thromb Res 18: 19–31PubMedCrossRefGoogle Scholar
  20. 20.
    Sandset PM, Roise O, Aasen A, Abildgaard U (1989) Extrinsic pathway inhibitor in postoperative/posttraumatic septicemia: increased levels in fatal cases. Haemostasis 19: 189–195PubMedGoogle Scholar
  21. 21.
    Sas G (1990) The biology of antithrombins. CRC, Boca RatonGoogle Scholar
  22. 22.
    Seitz R, Wolf M, Egbring R, Havemann K (1989) The disturbance of hemostasis in septic shock: role of neutrophil elastase and thrombin, effects of antithrombin III and plasma substitution. Eur J Haematol 43: 22–26PubMedCrossRefGoogle Scholar
  23. 23.
    Siebeck M, Hoffmann H, Weipert J, Fritz H (1992) Effect of elastase inhibitor eglin C in porcine endotoxin shock. Circ Shock 36:174–179PubMedGoogle Scholar
  24. 24.
    Spannagl M, Hoffmann H, Siebeck M, Weipert J, Schwarz HP, Schramm W (1991) A purified antithrombin III-heparin complex as a potent inhibitor of thrombin in endotoxin shock. Thromb Res 61: 1–10PubMedCrossRefGoogle Scholar
  25. 25.
    Taylor FB, Chang A, Esmon CT, D’Angelo A, Vigano-D’Angelo S, Blick KE (1987) Protein C prevents the coagulopathic and lethal effects of Escherichia coli infusion in the baboon. J Clin Invest 79: 918–925PubMedCrossRefGoogle Scholar
  26. 26.
    Van der Poll T, Büller HR, ten Cate H, Wortel CH, Bauer KA, Van Deventer SJH, Hack E, Sauerwein HP, Rosenberg RD, Cate JW ten (1990) Activation of coagulation after administration of tumor necrosis factor to normal subjects. N Engl J Med 322:1622–1627PubMedCrossRefGoogle Scholar
  27. 27.
    Van der Poll T, Levi M, Büller HR, van Deventer SJH, de Boer JP, Hack CE, Cate JW ten (1991) Fibrinolytic response to tumor necrosis factor in healthy subjects. J Exp Med 174: 729–732PubMedCrossRefGoogle Scholar
  28. 28.
    Wilson RF, Farag A, Mammen EF, Fujii Y (1988) Sepsis and antithrombin III, prekal-likrein, and fibronectin levels in surgical patients. Am Surg 55: 450–456Google Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1996

Authors and Affiliations

  • D. Inthorn

There are no affiliations available

Personalised recommendations