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Normalization of Plasma Antithrombin Activity in Patients Requiring Hemodynamic and/or Respiratory Support has Anti-inflammatory Properties Related to Survival

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Fachübergreifende Aspekte der Hämostaseologie IV

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Abstract

The Italian Antithrombin Sepsis Study has shown that maintenance of antithrombin (AT) levels around 100% results in a 53% reduction in the 30-day mortality risk of intensive care unit patients with sepsis and/or post-surgical complications requiring hemodynamic and/or respiratory support [1, 2]. The changes in a series of coagulation and fibrinolysis parameters were evaluated with the aim of correlating such changes with the potential effect of AT treatment on survival and exploring the predictive value of laboratory tests on 30-day mortality [3]. Blood samples from 119 patients were taken at baseline and then daily until day 7 from the beginning of AT or placebo infusion. The parameters evaluated were: AT activity, protein C (PC) and S activity and antigen levels, α2-antiplasmin and plasminogen activity, fibrin and fibrinogen degradation products, plasmin-antiplasmin complex, prothrombin fragment 1.2, and thrombin-antithrombin (TAT) complex. Prealbumin was also measured to correct for impaired liver synthesis of coagulation and fibrinolysis factors and inhibitors. Improvement — but never normalization — in most of the laboratory parameters was observed over time. In addition to AT, treatment only affected TAT levels (p = 0.05). In a Cox survival regression model, including the presence of septic shock, the multiorgan failure (MOF) score and the type of treatment as covariates, baseline AT levels were an independent predictor of mortality in the entire series of patients (p = 0.003). After 24 h of treatment, TAT levels were negatively associated with survival (p = 0.05). On the last day of treatment, the levels of PC (p = 0.006) and of fibrinogen-degradation products (p = 0.005) were negatively and positively associated with mortality in the 91 survivors [3].

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References

  1. Baudo F, Caimi T, deCataldo F, Ravizza A, Arlati S, Casella G, Carugo D, Palareti G, Leg-nani C, Ridolfi L, Rossi R, D’Angelo A, Grippa L, Giudici D, Gallioli G, Wolfer A, Calori G (1998) Antithrombin III (AT III) replacement therapy in patients with sepsis and/or postsurgical complications: a controlled double blind, randomized multicenter study. Intensive Care Med 24:336

    Article  PubMed  CAS  Google Scholar 

  2. Giudici D, Ravizza A, Ridolfi L, Baudo F, Palareti G, D’ Angelo A (1999) Antithrombin replacement in patients with sepsis and septic shock. Haematologica 84:452

    PubMed  CAS  Google Scholar 

  3. D’Angelo A, Palareti G (1996) The italian antithrombin III sepsis study: laboratory aspects. Second International Winter Meeting on Coagulation: Basic, Laboratory and Clinical Aspects of Thromboembolic Diseases. La Thuile, Italy. (Abstract 25)

    Google Scholar 

  4. Rosenberg RD (1989) Biochemistry of heparin antithrombin interactions, and the physiological role of this natural anticoagulant mechanisms. Am J Med 87:2 S [Suppl 3b]

    Article  Google Scholar 

  5. Granger DN, Kubes P (1994) The microcirculation and inflammation: modulation of leukocyte-endothelial cell adhesion. J Leukoc Biol 55: 662

    PubMed  CAS  Google Scholar 

  6. Horie S, Ishii H, Kazama M (1990) Heparin-like glycosaminoglycan is a receptor for antithrombin III-dependent but not for thrombin-dependent prostacyclin production in human endothelial cells. Thromb Res 59: 895

    Article  PubMed  CAS  Google Scholar 

  7. Yamauchi T, Umeda F, Inoguchi T, Nawata H (1989) Antithrombin III stimulates prostacyclin production by cultured aortic endothelial cells. Biochem Biophys Res Commun 163:1404

    Article  PubMed  CAS  Google Scholar 

  8. Eisenhut T, Shina B, Grottrup-Wolfers E, Semmler J, Siess W, Endres S (1993) Prostacyclin analogs suppress the synthesis of tumor necrosis factor-aa in LPS-stimulated human peripheral blood mononuclear cells. Immunopharmacology 26:259

    Article  PubMed  CAS  Google Scholar 

  9. Kainoh M, Imai R, Umetsu T, Hattori M, Nishio S (1990) Prostacyclin and beraprost sodium as suppressors of activated rat polymorphonuclear leukocytes. Biochem Pharmacol 39: 477

    Article  PubMed  CAS  Google Scholar 

  10. Boxer LA, Allen JM, Schmidt M, Yoder M, Baehner RL (1990) Inhibition of polymorphonuclear leukocyte adherence by prostacyclin. J Lab Clin Med 95: 672

    Google Scholar 

  11. Starkey PM (1977) Elastase and cathepsin G: the serine proteases of human neutrophil leukocytes and spleen. In: Barret AJ (ed) Proteinases in mammalian cells and tissues. Elsevier/North Holland, Amsterdam, p 57

    Google Scholar 

  12. Weiss SJ, LoBuglio AF (1980) An oxygen-dependent mechanism of neutrophil-mediated cytotoxicity. Blood 55:1020

    PubMed  CAS  Google Scholar 

  13. Weiss SJ, Young J, LoBuglio AF, Slivka A, Nimeh NF (1981) Role of hydrogen peroxide in neutrophil-mediated destruction of cultured endothelial cells. J Clin Invest 68: 714

    Article  PubMed  CAS  Google Scholar 

  14. Komatsu H, Koo A, Ghadishah E, Zeng H, Kuhlenkamp JF, Inoue M, Guth PH, Kaplowitz N (1992) Neutrophil accumulation in ischemic reperfused rat liver: evidence for a role for superoxide free radicals. Am J Physiol 262: G699

    Google Scholar 

  15. Jaeschke H, Bautista AP, Spolarics Z, Spitzer JJ (1992) Superoxide generation by neutrophils and kuppfer cells during in vivo reperfusion after hepatic ischemia in rats. J Leukoc Biol 52:377

    PubMed  CAS  Google Scholar 

  16. Colleti LM, Burtch GD, Remick DG, Strieter RM, Guice KS, Oldham KT, Campbell DA Jr (1990) The production of tumor necrosis factor as and the development of a pulmonary capillary injury following heaptic ischemia/reperfusion. Transplantation 49: 268

    Article  Google Scholar 

  17. Shito M, Wakabayashi G, Ueda M, Shimazu M, Shirasugi N, Endo M, Mukai M, Kitajima M (1997) Interleukin 1 receptor blockade reduces tumor necrosis factor production, tissue injury, and mortality after hepatic iscehmia-reperfusion in the rat. Transplantation 63:143

    Article  PubMed  CAS  Google Scholar 

  18. 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: 27 S

    Article  Google Scholar 

  19. Triantaphyllopoulos DC (1984) Effect of human antithrombin III on mortality and blood coagulation induced in rabbits by endotoxin. Thromb Haemost 51: 232

    PubMed  CAS  Google Scholar 

  20. Uchiba M, Okaijma K, Murakami K, Okabe H, Takatsuki K (1996) Attenuation of endotoxin-induced pulmonary vascular injury by antithrombin III. Am J Physiol 270: L921

    PubMed  CAS  Google Scholar 

  21. Harada N, Okaijima K, Kushimoto S, Isobe H, Tanaka K (1999) Antithrombin reduces ischemia/reperfusion injury of rat liver by increasing the hepatic level of prostacyclin. Blood 93:157

    PubMed  CAS  Google Scholar 

  22. Baggiolini M, Walz A, Kunkel SL (1989) Neutrophil-activating peptide 1/interleukin 8, a novel cytokine that activates neutrophils. J Clin Invest 84:1045

    Article  PubMed  CAS  Google Scholar 

  23. Baggiolini M, Clark-Lewis I (1992) Interleukin-8, a chemotactic and inflammatory cytokine. FEBS Lett 307: 97

    Article  PubMed  CAS  Google Scholar 

  24. Hisama H, Yamaguchi Y, Okaijima K, Uchiba M, Murakami M, Mori K, Yamada S, Ogawa M (1996) Anticoagulant pretreatment attenuates production of cytokine-induced neutrophil chemoattractant following ischemia-reperfusion of rat liver. Dig Dis Sci 41: 1481

    Article  PubMed  CAS  Google Scholar 

  25. Jochum M (1995) Influence of high-dose antithrombin concentrate therapy on the release of cellular proteinases, cytokines, and soluble adhesion molecules in acute infalmmation. Semin Hematol 32:19

    PubMed  CAS  Google Scholar 

  26. 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

    Article  PubMed  CAS  Google Scholar 

  27. American College of Chest Physiscians/Society of Critical Care Medicine Consensus Conference (1992) Definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis. Crit Care Med 20:864

    Article  Google Scholar 

  28. Kurosawa S, Stearns-Kurosawa DJ, Carson CW, D’Angelo A, Della Valle P, Esmon CT (1998) Plasma levels of endothelial cell protein C receptor are elevated in patients with sepsis and systemic lupus erythematosus: lack of correlation with thrombomodulin suggests involvment of different pathological processes. Blood 91:725

    PubMed  CAS  Google Scholar 

  29. Beutler B, Cerami A (1987) Cachectin: more than a tumor necrosis factor. New Engl J Med 316:379

    Article  PubMed  CAS  Google Scholar 

  30. Tracey KJ, Fong Y, Hesse DG, Manogue KR, Lee AT, Kuo GC, Lowry SF, Cerami A (1987) Anti cachectin/TNF monoclonal antibodies prevent septic shock during lethal bacteraemia. Nature 330: 662

    Article  PubMed  CAS  Google Scholar 

  31. Waage A, Halstensen A, Espevik T (1987) Association between tumor necrosis factor in serum and fatal outcome in patients with meningococcal disease. Lancet 1:335

    Google Scholar 

  32. Oppenheim JJ, Gery L (1982) Interleukin-1 is more than an interleukin. Immunology Today 3:113

    Article  CAS  Google Scholar 

  33. Bailly S et al.(1994) Comparative production of IL-10 and IL-laa by LPS-stimulated human monocytes: ELISAs measurements revisited. Cytokine 6:111

    Article  PubMed  CAS  Google Scholar 

  34. Mizel SB (1982) Interleukin-1 and T-cell activation. Immunol Rev 63:51

    Article  PubMed  CAS  Google Scholar 

  35. Dinarello CA (1985) An update of human interleukin-1: from molecular biology to clinical relevance. J Clin Immunol 5: 287

    Article  PubMed  CAS  Google Scholar 

  36. Dinarello CA (1984) Interleukin-1 and the pathogenesis of the acute phase response. N Eng1 J Med 311:1413

    Article  CAS  Google Scholar 

  37. Moscovitz H et al.(1994) Plasma cytokine determination in emergency department patients as predictor of bacteremia and infectious disease severity. Crit Care Med 22: 1102

    Article  PubMed  CAS  Google Scholar 

  38. Baggiolini M et al.(1989) Neutrophil-activating peptide-1/interleukin-8, a novel cytokine that activates neutrophils. J Clin Invest 84:1045

    Article  PubMed  CAS  Google Scholar 

  39. Hack C et al.(1992) Interleukin-8 in sepsis: relation to shock and inflammatory mediators. Infect Immun 60: 2835

    PubMed  CAS  Google Scholar 

  40. Banchereau J (1990) Interleukin-4. Medecine/Science 6:946

    Google Scholar 

  41. Briscoe DM, Cotran RS, Pober JS (1992) Effects of tumor necrosis factor, lipopolysaccharide and IL-4 on the expression of vascular cell adhesion molecules-1 in vivo: correlation with CD3+ T cell infiltration. J Immunol 149: 2954

    PubMed  CAS  Google Scholar 

  42. Bogdan C, Bodovotz Y, Nathan C (1991) Macrophage deactivation by interleukin-10. J Exp Med 174:1549

    Article  PubMed  CAS  Google Scholar 

  43. Marchant A, Deviere J, Byl B, De Groote D, Vincent JL, Goldman M (1994) Interleukin10 production during septicaemia. Lancet 343:707

    Article  PubMed  CAS  Google Scholar 

  44. Lasky LA (1992) Selectins: interpreters of cell-specific carbohydrate information during inflammation. Science 964

    Google Scholar 

  45. Cotran RS, Gimbrone MA Jr, Bevilacqua MP, Mendrick DL, Pober JS (1986) Induction and detection of a human endothelial activation antigen in vivo. J Exp Med 164:661

    Article  PubMed  CAS  Google Scholar 

  46. Elices MJ, Osborn L, Takada Y, Crouse C, Luhowskyj S, Hemler ME, Lobb RR (1990) VCAM-1 on activated endothelium interacts with the leukocyte integrin VLA-4 at a site distinct from the VLA-fibronectin binding site. Cell 60: 577

    Article  PubMed  CAS  Google Scholar 

  47. Bevilacqua MP, Stengelin S, Gimbrone MA Jr, Seed B (1989) Endothelial leukocyte adhesion molecule 1: an inducible receptor for neutrophils related to complement regulatory proteins and lectins. Science 243:1160

    Article  PubMed  CAS  Google Scholar 

  48. Osborn L, Hession C, Tizard R, Vassalo C, Luhovskyj S, Chi-Rosso G, Lobb RR (1989) Direct expression cloning of vascular cell adhesion molecule 1, a cytokine-induced endothelial protein that binds to lymphocytes. Cell 59:1203

    Article  PubMed  CAS  Google Scholar 

  49. Fries JWU, Williams AJ, Atkins RC, Newman W, Lipscomb MF, Collins T (1993) Expression of VCAM-1 and E-selectin in an in vivo model of endothelial activation. Am J Pathol 143:725

    PubMed  CAS  Google Scholar 

  50. Fukudome K, Esmon CT (1994) Identification, cloning and regulation of a novel endothelial cell-protein C/activated protein C receptor. J Biol Chem 269:26486

    PubMed  CAS  Google Scholar 

  51. Regan LM, Stearns-Kurosawa DJ, Kurosawa S, Mollica J, Fukudome K, Esmon CT (1994) The endothelial cell protein C receptor: inhibition of activated protein C anticoagulant function without modulation of reaction with proteinase inhibitors. J Biol Chem 271: 17499

    Google Scholar 

  52. Laszik Z, Mitro A, Taylor FB Jr, Ferrel G, Esmon CT (1997) The human protein C receptor is present primarily on endothelium of large blood vessels: implications for the control of the protein C pathway. Circulation 96:3633

    PubMed  CAS  Google Scholar 

  53. Stearns-Kurosawa DJ, Kurosawa S, Mollica JS, Ferrell GL, Esmon CT (1996) The endothelial cell protein C receptor augments protein C activation by the thrombin-thrombomodulin complex. Proc Natl Acad Sci USA 93: 10212

    Article  PubMed  CAS  Google Scholar 

  54. Kurosawa S, Stearns-Kurosawa DJ, Hidari N, Esmon CT (1997) Identification of functional endothelial protein C receptor in human plasma. J Clin Invest 100:411

    Article  PubMed  CAS  Google Scholar 

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Authors
  1. A. D’Angelo
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  2. P. Della Valle
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  3. C. Legnani
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  4. G. Palareti
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  5. A. Ravizza
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  6. L. Ridolfi
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  7. D. Giudici
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  8. F. Baudo
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  9. S. Kurosawa
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Editors and Affiliations

  1. Klinik für Anästhesiologie, Universität Heidelberg, Im Neuenheimer Feld 110, D-69120, Heidelberg, Deutschland

    Eike Martin

  2. Sektion Vaskuläre Medizin Medizinische Klinik IV und Poliklinik, Universitätsklinikum Tübingen, Otfried-Müller-Straße 10, D-72076, Tübingen, Deutschland

    Peter Nawroth

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© 1999 Springer-Verlag Berlin Heidelberg

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D’Angelo, A. et al. (1999). Normalization of Plasma Antithrombin Activity in Patients Requiring Hemodynamic and/or Respiratory Support has Anti-inflammatory Properties Related to Survival. In: Martin, E., Nawroth, P. (eds) Fachübergreifende Aspekte der Hämostaseologie IV. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-60239-9_6

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  • DOI: https://doi.org/10.1007/978-3-642-60239-9_6

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-540-66317-1

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