Skip to main content
Erschienen in: Critical Care 1/2006

01.02.2006 | Review

Clinical review: Molecular mechanisms underlying the role of antithrombin in sepsis

verfasst von: Christian J Wiedermann

Erschienen in: Critical Care | Ausgabe 1/2006

Einloggen, um Zugang zu erhalten

Abstract

In disseminated intravascular coagulation (DIC) there is extensive crosstalk between activation of inflammation and coagulation. Endogenous anticoagulatory pathways are downregulated by inflammation, thus decreasing the natural anti-inflammatory mechanisms that these pathways possess. Supportive strategies aimed at inhibiting activation of coagulation and inflammation may theoretically be justified and have been found to be beneficial in experimental and initial clinical studies. This review assembles the available experimental and clinical data on biological mechanisms of antithrombin in inflammatory coagulation activation. Preclinical research has demonstrated partial interference of heparin – administered even at low doses – with the therapeutic effects of antithrombin, and has confirmed – at the level of cellular mechanisms – a regulatory role for antithrombin in DIC. Against this biological background, re-analyses of data from randomized controlled trials of antithrombin in sepsis suggest that antithrombin has the potential to be developed further as a therapeutic agent in the treatment of DIC. Even though there is a lack of studies employing satisfactory methodology, the results of investigations conducted thus far into the mechanisms of action of antithrombin allow one to infer that there is biological plausibility in the value of this agent. Final assessment of the drug's effectiveness, however, must await the availability of positive, prospective, randomized and placebo-controlled studies.
Literatur
1.
Zurück zum Zitat Rosenberg RD, Bauer KA: Thrombosis in inherited deficiencies of antithrombin, protein C, and protein S. Hum Pathol 1987, 18: 253-262.CrossRefPubMed Rosenberg RD, Bauer KA: Thrombosis in inherited deficiencies of antithrombin, protein C, and protein S. Hum Pathol 1987, 18: 253-262.CrossRefPubMed
2.
Zurück zum Zitat Hauptman JG, Hassouna HI, Bell TG, Penner JA, Emerson TE: Efficacy of antithrombin III in endotoxin-induced disseminated intravascular coagulation. Circ Shock 1988, 25: 111-122.PubMed Hauptman JG, Hassouna HI, Bell TG, Penner JA, Emerson TE: Efficacy of antithrombin III in endotoxin-induced disseminated intravascular coagulation. Circ Shock 1988, 25: 111-122.PubMed
3.
Zurück zum Zitat Hiller E, Pihusch R: Thrombophilia caused by congenital disorders of blood coagulation. Fortschr Med 1998, 116: 26-32.PubMed Hiller E, Pihusch R: Thrombophilia caused by congenital disorders of blood coagulation. Fortschr Med 1998, 116: 26-32.PubMed
4.
Zurück zum Zitat Mammen EF: The role of antithrombin III in DIC. Biol Clin Haematol 1987, (Suppl 1):69-73. Mammen EF: The role of antithrombin III in DIC. Biol Clin Haematol 1987, (Suppl 1):69-73.
5.
Zurück zum Zitat de Jonge E, Levi M, Stoutenbeek CP, van Deventer SJ: Current drug treatment strategies for disseminated intravascular coagulation. Drugs 1998, 55: 767-777. 10.2165/00003495-199855060-00004CrossRefPubMed de Jonge E, Levi M, Stoutenbeek CP, van Deventer SJ: Current drug treatment strategies for disseminated intravascular coagulation. Drugs 1998, 55: 767-777. 10.2165/00003495-199855060-00004CrossRefPubMed
6.
Zurück zum Zitat Mammen EF, Miyakawa T, Phillips TF, Assarian GS, Brown JM, Murano G: Human antithrombin concentrates and experimental disseminated intravascular coagulation. Semin Thromb Hemost 1985, 11: 373-383.CrossRefPubMed Mammen EF, Miyakawa T, Phillips TF, Assarian GS, Brown JM, Murano G: Human antithrombin concentrates and experimental disseminated intravascular coagulation. Semin Thromb Hemost 1985, 11: 373-383.CrossRefPubMed
7.
Zurück zum Zitat Levi M, Ten Cate H: Disseminated intravascular coagulation. N Engl J Med 1999, 341: 586-592. 10.1056/NEJM199908193410807CrossRefPubMed Levi M, Ten Cate H: Disseminated intravascular coagulation. N Engl J Med 1999, 341: 586-592. 10.1056/NEJM199908193410807CrossRefPubMed
8.
Zurück zum Zitat Schregel W, Straub H, Wolk G, Schneider R: Successful therapy of consumption coagulopathy in EPH gestosis with multiple organ failure [in German]. Anasth Intensivther Not-fallmed 1984, 19: 201-203.CrossRef Schregel W, Straub H, Wolk G, Schneider R: Successful therapy of consumption coagulopathy in EPH gestosis with multiple organ failure [in German]. Anasth Intensivther Not-fallmed 1984, 19: 201-203.CrossRef
9.
Zurück zum Zitat Dickneite G, Paques EP: Reduction of mortality with antithrombin III in septicemic rats: a study of Klebsiella pneumoniae-induced sepsis. Thromb Haemost 1993, 69: 98-102.PubMed Dickneite G, Paques EP: Reduction of mortality with antithrombin III in septicemic rats: a study of Klebsiella pneumoniae-induced sepsis. Thromb Haemost 1993, 69: 98-102.PubMed
10.
Zurück zum Zitat Emerson TE Jr, Fournel MA, Leach WJ, Redens TB: Protection against disseminated intravascular coagulation and death by antithrombin-III in the Escherichia coli endotoxemic rat. Circ Shock 1987, 21: 1-13.PubMed Emerson TE Jr, Fournel MA, Leach WJ, Redens TB: Protection against disseminated intravascular coagulation and death by antithrombin-III in the Escherichia coli endotoxemic rat. Circ Shock 1987, 21: 1-13.PubMed
11.
Zurück zum Zitat Redens TB, Leach WJ, Bogdanoff DA, Emerson TE Jr: Synergistic protection from lung damage by combining antithrombin-III and alpha-1-proteinase inhibitor in the E. coli endotoxemic sheep pulmonary dysfunction model. Circ Shock 1988, 26: 15-26.PubMed Redens TB, Leach WJ, Bogdanoff DA, Emerson TE Jr: Synergistic protection from lung damage by combining antithrombin-III and alpha-1-proteinase inhibitor in the E. coli endotoxemic sheep pulmonary dysfunction model. Circ Shock 1988, 26: 15-26.PubMed
12.
Zurück zum Zitat Ronneberger H, Hein B: Effect of antithrombin III on experimental hepatotoxin poisoning in dogs [in German]. Arzneimittelforschung 1984, 34: 277-279.PubMed Ronneberger H, Hein B: Effect of antithrombin III on experimental hepatotoxin poisoning in dogs [in German]. Arzneimittelforschung 1984, 34: 277-279.PubMed
13.
Zurück zum Zitat Taylor FB Jr, Emerson TE Jr, Jordan R, Chang AK, Blick KE: Antithrombin-III prevents the lethal effects of Escherichia coli infusion in baboons. Circ Shock 1988, 26: 227-235.PubMed Taylor FB Jr, Emerson TE Jr, Jordan R, Chang AK, Blick KE: Antithrombin-III prevents the lethal effects of Escherichia coli infusion in baboons. Circ Shock 1988, 26: 227-235.PubMed
14.
Zurück zum Zitat Baudo F, Caimi TM, de Cataldo F, Ravizza A, Arlati S, Casella G, Carugo D, Palareti G, Legnani C, Ridolfi L, et al.: Antithrombin III (ATIII) replacement therapy in patients with sepsis and/or postsurgical complications: a controlled double-blind, randomized, multicenter study. Intensive Care Med 1998, 24: 336-342. 10.1007/s001340050576CrossRefPubMed Baudo F, Caimi TM, de Cataldo F, Ravizza A, Arlati S, Casella G, Carugo D, Palareti G, Legnani C, Ridolfi L, et al.: Antithrombin III (ATIII) replacement therapy in patients with sepsis and/or postsurgical complications: a controlled double-blind, randomized, multicenter study. Intensive Care Med 1998, 24: 336-342. 10.1007/s001340050576CrossRefPubMed
15.
Zurück zum Zitat Eisele B, Lamy M, Thijs LG, Keinecke HO, Schuster HP, Matthias FR, Fourrier F, Heinrichs H, Delvos U: Antithrombin III in patients with severe sepsis. A randomized, placebo-controlled, double-blind multicenter trial plus a meta-analysis on all randomized, placebo-controlled, double-blind trials with antithrombin III in severe sepsis. Intensive Care Med 1998, 24: 663-672. 10.1007/s001340050642CrossRefPubMed Eisele B, Lamy M, Thijs LG, Keinecke HO, Schuster HP, Matthias FR, Fourrier F, Heinrichs H, Delvos U: Antithrombin III in patients with severe sepsis. A randomized, placebo-controlled, double-blind multicenter trial plus a meta-analysis on all randomized, placebo-controlled, double-blind trials with antithrombin III in severe sepsis. Intensive Care Med 1998, 24: 663-672. 10.1007/s001340050642CrossRefPubMed
16.
Zurück zum Zitat Fourrier F, Chopin C, Huart JJ, Runge I, Caron C: Double-blind, placebo-controlled trial of antithrombin III concentrates in septic shock with disseminated intravascular coagulation. Chest 1993, 104: 882-888.CrossRefPubMed Fourrier F, Chopin C, Huart JJ, Runge I, Caron C: Double-blind, placebo-controlled trial of antithrombin III concentrates in septic shock with disseminated intravascular coagulation. Chest 1993, 104: 882-888.CrossRefPubMed
17.
Zurück zum Zitat Inthorn D, Hoffmann N, Hartl WH, Mühlbayer D, Jochum M: Effect of antithrombin III supplementation on inflammatory response in patients with severe sepsis. Shock 1998, 10: 90-96.CrossRefPubMed Inthorn D, Hoffmann N, Hartl WH, Mühlbayer D, Jochum M: Effect of antithrombin III supplementation on inflammatory response in patients with severe sepsis. Shock 1998, 10: 90-96.CrossRefPubMed
18.
Zurück zum Zitat Vinazzer H: Therapeutic use of antithrombin III in shock and disseminated intravascular coagulation. Semin Thromb Hemost 1989, 15: 347-352.CrossRefPubMed Vinazzer H: Therapeutic use of antithrombin III in shock and disseminated intravascular coagulation. Semin Thromb Hemost 1989, 15: 347-352.CrossRefPubMed
19.
Zurück zum Zitat Warren BL, Eid A, Singer P, Pillay SS, Carl P, Novak I, Chalupa P, Atherstone A, Penzes I, Kubler A, KyberSept Trial Study Group, et al.: Caring for the critically ill patient. High-dose antithrombin III in severe sepsis: a randomized controlled trial. JAMA 2001, 286: 1869-1878. 10.1001/jama.286.15.1869CrossRefPubMed Warren BL, Eid A, Singer P, Pillay SS, Carl P, Novak I, Chalupa P, Atherstone A, Penzes I, Kubler A, KyberSept Trial Study Group, et al.: Caring for the critically ill patient. High-dose antithrombin III in severe sepsis: a randomized controlled trial. JAMA 2001, 286: 1869-1878. 10.1001/jama.286.15.1869CrossRefPubMed
20.
Zurück zum Zitat Abildgaard U: Binding of thrombin to antithrombin III. Scand J Clin Lab Invest 1969, 24: 23-27.CrossRefPubMed Abildgaard U: Binding of thrombin to antithrombin III. Scand J Clin Lab Invest 1969, 24: 23-27.CrossRefPubMed
21.
Zurück zum Zitat Schuster HP, Eisele B, Keinecke HO: S-antithrombin III study: antithrombin III in patients with sepsis. Intensive Care Med 1998, (Suppl 1):76. Schuster HP, Eisele B, Keinecke HO: S-antithrombin III study: antithrombin III in patients with sepsis. Intensive Care Med 1998, (Suppl 1):76.
22.
Zurück zum Zitat Turk B, Brieditis I, Bock SC, Olson ST, Bjork I: The oligosaccharide side chain on Asn-135 of alpha-antithrombin, absent in beta-antithrombin, decreases the heparin affinity of the inhibitor by affecting the heparin-induced conformational change. Biochemistry 1997, 36: 6682-6691. 10.1021/bi9702492CrossRefPubMed Turk B, Brieditis I, Bock SC, Olson ST, Bjork I: The oligosaccharide side chain on Asn-135 of alpha-antithrombin, absent in beta-antithrombin, decreases the heparin affinity of the inhibitor by affecting the heparin-induced conformational change. Biochemistry 1997, 36: 6682-6691. 10.1021/bi9702492CrossRefPubMed
23.
Zurück zum Zitat Andersson LO, Engman L, Henningsson E: Crossed immuno-electrophoresis as applied to studies on complex formation. The binding of heparin to antithrombin III and the antithrombin III-thrombin complex. J Immunol Methods 1977, 14: 271-281. 10.1016/0022-1759(77)90138-7CrossRefPubMed Andersson LO, Engman L, Henningsson E: Crossed immuno-electrophoresis as applied to studies on complex formation. The binding of heparin to antithrombin III and the antithrombin III-thrombin complex. J Immunol Methods 1977, 14: 271-281. 10.1016/0022-1759(77)90138-7CrossRefPubMed
24.
Zurück zum Zitat Perlmutter DH, Glover GI, Rivetna M, Schasteen CS, Fallon RJ: Identification of a serpin-enzyme complex receptor on human hepatoma cells and human monocytes. Proc Natl Acad Sci USA 1990, 87: 3753-3757.PubMedCentralCrossRefPubMed Perlmutter DH, Glover GI, Rivetna M, Schasteen CS, Fallon RJ: Identification of a serpin-enzyme complex receptor on human hepatoma cells and human monocytes. Proc Natl Acad Sci USA 1990, 87: 3753-3757.PubMedCentralCrossRefPubMed
25.
Zurück zum Zitat Pizzo SV: Serpin receptor 1: a hepatic receptor that mediates the clearance of antithrombin III-proteinase complexes. Am J Med 1989, 87: 10S-14S. 10.1016/0002-9343(89)80524-8CrossRefPubMed Pizzo SV: Serpin receptor 1: a hepatic receptor that mediates the clearance of antithrombin III-proteinase complexes. Am J Med 1989, 87: 10S-14S. 10.1016/0002-9343(89)80524-8CrossRefPubMed
26.
Zurück zum Zitat Bombeli T, Mueller M, Haeberli A: Anticoagulant properties of the vascular endothelium. Thromb Haemost 1997, 77: 408-423.PubMed Bombeli T, Mueller M, Haeberli A: Anticoagulant properties of the vascular endothelium. Thromb Haemost 1997, 77: 408-423.PubMed
27.
Zurück zum Zitat Taylor FB Jr, Emerson TE Jr, Jordan R, Chang AK, Blick KE: Antithrombin-III prevents the lethal effects of Escherichia coli infusion in baboons. Circ Shock 1988, 26: 227-235.PubMed Taylor FB Jr, Emerson TE Jr, Jordan R, Chang AK, Blick KE: Antithrombin-III prevents the lethal effects of Escherichia coli infusion in baboons. Circ Shock 1988, 26: 227-235.PubMed
28.
Zurück zum Zitat Taylor FB Jr, Chang AC, Peer GT, Mather T, Blick K, Catlett R, Lockhart MS, Esmon CT: DEGR-factor Xa blocks disseminated intravascular coagulation initiated by Escherichia coli without preventing shock or organ damage. Blood 1991, 78: 364-368.PubMed Taylor FB Jr, Chang AC, Peer GT, Mather T, Blick K, Catlett R, Lockhart MS, Esmon CT: DEGR-factor Xa blocks disseminated intravascular coagulation initiated by Escherichia coli without preventing shock or organ damage. Blood 1991, 78: 364-368.PubMed
29.
Zurück zum Zitat Yamauchi T, Umeda F, Inoguchi T, Nawata H: Antithrombin III stimulates prostacyclin production by cultured aortic endothelial cells. Biochem Biophys Res Commun 1989, 163: 1404-1411. 10.1016/0006-291X(89)91135-2CrossRefPubMed Yamauchi T, Umeda F, Inoguchi T, Nawata H: Antithrombin III stimulates prostacyclin production by cultured aortic endothelial cells. Biochem Biophys Res Commun 1989, 163: 1404-1411. 10.1016/0006-291X(89)91135-2CrossRefPubMed
30.
Zurück zum Zitat Horie S, Ishii H, Kazama M: Heparin-like glycosaminoglycan is a receptor for antithrombin III-dependent but not for thrombin-dependent prostacyclin production in human endothelial cells. Thromb Res 1990, 59: 895-904. 10.1016/0049-3848(90)90113-QCrossRefPubMed Horie S, Ishii H, Kazama M: Heparin-like glycosaminoglycan is a receptor for antithrombin III-dependent but not for thrombin-dependent prostacyclin production in human endothelial cells. Thromb Res 1990, 59: 895-904. 10.1016/0049-3848(90)90113-QCrossRefPubMed
31.
Zurück zum Zitat Harada N, Okajima K, Kushimoto S, Isobe H, Tanaka K: Antithrombin reduces ischemia/reperfusion injury of rat liver by increasing the hepatic level of prostacyclin. Blood 1999, 93: 157-164.PubMed Harada N, Okajima K, Kushimoto S, Isobe H, Tanaka K: Antithrombin reduces ischemia/reperfusion injury of rat liver by increasing the hepatic level of prostacyclin. Blood 1999, 93: 157-164.PubMed
32.
Zurück zum Zitat Uchiba M, Okajima K, Murakami K, Okabe H, Takatsuki K: Attenuation of endotoxin-induced pulmonary vascular injury by antithrombin III. Am J Physiol 1996, 270: L921-L930.PubMed Uchiba M, Okajima K, Murakami K, Okabe H, Takatsuki K: Attenuation of endotoxin-induced pulmonary vascular injury by antithrombin III. Am J Physiol 1996, 270: L921-L930.PubMed
33.
Zurück zum Zitat Ostrovsky L, Woodman RC, Payne D, Teoh D, Kubes P: Antithrombin III prevents and rapidly reverses leukocyte recruitment in ischemia/reperfusion. Circulation 1997, 96: 2302-2310.CrossRefPubMed Ostrovsky L, Woodman RC, Payne D, Teoh D, Kubes P: Antithrombin III prevents and rapidly reverses leukocyte recruitment in ischemia/reperfusion. Circulation 1997, 96: 2302-2310.CrossRefPubMed
34.
Zurück zum Zitat Hoffmann JN, Vollmar B, Inthorn D, Schildberg FW, Menger MD: Antithrombin reduces leukocyte adhesion during chronic endotoxemia by modulation of the cyclooxygenase pathway. Am J Physiol Cell Physiol 2000, 279: C98-C107.PubMed Hoffmann JN, Vollmar B, Inthorn D, Schildberg FW, Menger MD: Antithrombin reduces leukocyte adhesion during chronic endotoxemia by modulation of the cyclooxygenase pathway. Am J Physiol Cell Physiol 2000, 279: C98-C107.PubMed
35.
Zurück zum Zitat Neviere R, Tournoys A, Mordon S, Marechal X, Song FL, Jourdain M, Fourrier F: Antithrombin reduces mesenteric venular leukocyte interactions and small intestine injury in endotoxemic rats. Shock 2001, 15: 220-225.CrossRefPubMed Neviere R, Tournoys A, Mordon S, Marechal X, Song FL, Jourdain M, Fourrier F: Antithrombin reduces mesenteric venular leukocyte interactions and small intestine injury in endotoxemic rats. Shock 2001, 15: 220-225.CrossRefPubMed
36.
Zurück zum Zitat Kaneider NC, Reinisch CM, Dunzendorfer S, Romisch J, Wieder-mann CJ: Syndecan-4 mediates antithrombin-induced chemotaxis of human peripheral blood lymphocytes and monocytes. J Cell Sci 2002, 115: 227-236.PubMed Kaneider NC, Reinisch CM, Dunzendorfer S, Romisch J, Wieder-mann CJ: Syndecan-4 mediates antithrombin-induced chemotaxis of human peripheral blood lymphocytes and monocytes. J Cell Sci 2002, 115: 227-236.PubMed
37.
Zurück zum Zitat Kaneider NC, Egger P, Dunzendorfer S, Wiedermann CJ: Syndecan-4 as antithrombin receptor of human neutrophils. Biochem Biophys Res Commun 2001, 287: 424-426. 10.1006/bbrc.2001.5534 Kaneider NC, Egger P, Dunzendorfer S, Wiedermann CJ: Syndecan-4 as antithrombin receptor of human neutrophils. Biochem Biophys Res Commun 2001, 287: 424-426. 10.1006/bbrc.2001.5534
38.
Zurück zum Zitat Dunzendorfer S, Kaneider N, Rabensteiner A, Meierhofer C, Reinisch C, Romisch J, Wiedermann CJ: Cell-surface heparan sulfate proteoglycan-mediated regulation of human neu-trophil migration by the serpin antithrombin III. Blood 2001, 97: 1079-1085. 10.1182/blood.V97.4.1079CrossRefPubMed Dunzendorfer S, Kaneider N, Rabensteiner A, Meierhofer C, Reinisch C, Romisch J, Wiedermann CJ: Cell-surface heparan sulfate proteoglycan-mediated regulation of human neu-trophil migration by the serpin antithrombin III. Blood 2001, 97: 1079-1085. 10.1182/blood.V97.4.1079CrossRefPubMed
39.
Zurück zum Zitat Mizutani A, Okajima K, Uchiba M, Isobe H, Harada N, Mizutani S, Noguchi T: Antithrombin reduces ischemia/reperfusion-induced renal injury in rats by inhibiting leukocyte activation through promotion of prostacyclin production. Blood 2003, 101: 3029-3036. 10.1182/blood-2002-08-2406CrossRefPubMed Mizutani A, Okajima K, Uchiba M, Isobe H, Harada N, Mizutani S, Noguchi T: Antithrombin reduces ischemia/reperfusion-induced renal injury in rats by inhibiting leukocyte activation through promotion of prostacyclin production. Blood 2003, 101: 3029-3036. 10.1182/blood-2002-08-2406CrossRefPubMed
40.
Zurück zum Zitat Harada N, Okajima K, Uchiba M, Kushimoto S, Isobe H: Antithrombin reduces ischemia/reperfusion-induced liver injury in rats by activation of cyclooxygenase-1. Thromb Haemost 2004, 92: 550-558.PubMed Harada N, Okajima K, Uchiba M, Kushimoto S, Isobe H: Antithrombin reduces ischemia/reperfusion-induced liver injury in rats by activation of cyclooxygenase-1. Thromb Haemost 2004, 92: 550-558.PubMed
41.
Zurück zum Zitat Hirose K, Okajima K, Uchiba M, Nakano KY, Utoh J, Kitamura N: Antithrombin reduces the ischemia/reperfusion-induced spinal cord injury in rats by attenuating inflammatory responses. Thromb Haemost 2004, 91: 162-170.PubMed Hirose K, Okajima K, Uchiba M, Nakano KY, Utoh J, Kitamura N: Antithrombin reduces the ischemia/reperfusion-induced spinal cord injury in rats by attenuating inflammatory responses. Thromb Haemost 2004, 91: 162-170.PubMed
42.
Zurück zum Zitat Taoka Y, Okajima K, Uchiba M: Antithrombin reduces compression-induced spinal cord injury in rats. J Neurotrauma 2004, 21: 1818-1830. 10.1089/neu.2004.21.1818CrossRefPubMed Taoka Y, Okajima K, Uchiba M: Antithrombin reduces compression-induced spinal cord injury in rats. J Neurotrauma 2004, 21: 1818-1830. 10.1089/neu.2004.21.1818CrossRefPubMed
43.
Zurück zum Zitat Feistritzer C, Kaneider NC, Sturn DH, Wiedermann CJ: Syndecan-4-dependent migration of human eosinophils. Clin Exp Allergy 2004, 34: 696-703. 10.1111/j.1365-2222.2004.1853.xCrossRefPubMed Feistritzer C, Kaneider NC, Sturn DH, Wiedermann CJ: Syndecan-4-dependent migration of human eosinophils. Clin Exp Allergy 2004, 34: 696-703. 10.1111/j.1365-2222.2004.1853.xCrossRefPubMed
44.
Zurück zum Zitat Olson ST, Bjork I, Sheffer R, Craig PA, Shore JD, Choay J: Role of the antithrombin-binding pentasaccharide in heparin acceleration of antithrombin-proteinase reactions. Resolution of the antithrombin conformational change contribution to heparin rate enhancement. J Biol Chem 1992, 267: 12528-12538.PubMed Olson ST, Bjork I, Sheffer R, Craig PA, Shore JD, Choay J: Role of the antithrombin-binding pentasaccharide in heparin acceleration of antithrombin-proteinase reactions. Resolution of the antithrombin conformational change contribution to heparin rate enhancement. J Biol Chem 1992, 267: 12528-12538.PubMed
45.
Zurück zum Zitat Ishiguro K, Kojima T, Muramatsu T: Syndecan-4 as a molecule involved in defense mechanisms. Glycoconj J 2002, 19: 315-318. 10.1023/A:1025308702966CrossRefPubMed Ishiguro K, Kojima T, Muramatsu T: Syndecan-4 as a molecule involved in defense mechanisms. Glycoconj J 2002, 19: 315-318. 10.1023/A:1025308702966CrossRefPubMed
46.
Zurück zum Zitat Hoffmann JN, Vollmar B, Laschke MW, Inthorn D, Kaneider NC, Dunzendorfer S, Wiedermann CJ, Romisch J, Schildberg FW, Menger MD: Adverse effect of heparin on antithrombin action during endotoxemia: microhemodynamic and cellular mechanisms. Thromb Haemost 2002, 88: 242-252.PubMed Hoffmann JN, Vollmar B, Laschke MW, Inthorn D, Kaneider NC, Dunzendorfer S, Wiedermann CJ, Romisch J, Schildberg FW, Menger MD: Adverse effect of heparin on antithrombin action during endotoxemia: microhemodynamic and cellular mechanisms. Thromb Haemost 2002, 88: 242-252.PubMed
47.
Zurück zum Zitat Kaneider NC, Forster E, Mosheimer B, Sturn DH, Wiedermann CJ: Syndecan-4-dependent signaling in the inhibition of endotoxin-induced endothelial adherence of neutrophils by antithrombin. Thromb Haemost 2003, 90: 1150-1157.PubMed Kaneider NC, Forster E, Mosheimer B, Sturn DH, Wiedermann CJ: Syndecan-4-dependent signaling in the inhibition of endotoxin-induced endothelial adherence of neutrophils by antithrombin. Thromb Haemost 2003, 90: 1150-1157.PubMed
48.
Zurück zum Zitat Oelschlager C, Romisch J, Staubitz A, Stauss H, Leithauser B, Tillmanns H, Holschermann H: Antithrombin III inhibits nuclear factor kappaB activation in human monocytes and vascular endothelial cells. Blood 2002, 99: 4015-4020. 10.1182/blood.V99.11.4015CrossRefPubMed Oelschlager C, Romisch J, Staubitz A, Stauss H, Leithauser B, Tillmanns H, Holschermann H: Antithrombin III inhibits nuclear factor kappaB activation in human monocytes and vascular endothelial cells. Blood 2002, 99: 4015-4020. 10.1182/blood.V99.11.4015CrossRefPubMed
49.
Zurück zum Zitat Mansell A, Reinicke A, Worrall DM, O'Neill LA: The serine protease inhibitor antithrombin III inhibits LPS-mediated NF-kappaB activation by TLR-4. FEBS Lett 2001, 508: 313-317. 10.1016/S0014-5793(01)03077-0CrossRefPubMed Mansell A, Reinicke A, Worrall DM, O'Neill LA: The serine protease inhibitor antithrombin III inhibits LPS-mediated NF-kappaB activation by TLR-4. FEBS Lett 2001, 508: 313-317. 10.1016/S0014-5793(01)03077-0CrossRefPubMed
50.
Zurück zum Zitat Hatada EN, Krappmann D, Scheidereit C: NF-kappaB and the innate immune response. Curr Opin Immunol 2000, 12: 52-58. 10.1016/S0952-7915(99)00050-3CrossRefPubMed Hatada EN, Krappmann D, Scheidereit C: NF-kappaB and the innate immune response. Curr Opin Immunol 2000, 12: 52-58. 10.1016/S0952-7915(99)00050-3CrossRefPubMed
51.
Zurück zum Zitat Minnema MC, Chang AC, Jansen PM, Lubbers YT, Pratt BM, Whittaker BG, Taylor FB, Hack CE, Friedman B: Recombinant human antithrombin III improves survival and attenuates inflammatory responses in baboons lethally challenged with Escherichia coli . Blood 2000, 95: 1117-1123.PubMed Minnema MC, Chang AC, Jansen PM, Lubbers YT, Pratt BM, Whittaker BG, Taylor FB, Hack CE, Friedman B: Recombinant human antithrombin III improves survival and attenuates inflammatory responses in baboons lethally challenged with Escherichia coli . Blood 2000, 95: 1117-1123.PubMed
52.
Zurück zum Zitat Souter PJ, Thomas S, Hubbard AR, Poole S, Romisch J, Gray E: Antithrombin inhibits lipopolysaccharide-induced tissue factor and interleukin-6 production by mononuclear cells, human umbilical vein endothelial cells, and whole blood. Crit Care Med 2001, 29: 134-139. 10.1097/00003246-200101000-00027CrossRefPubMed Souter PJ, Thomas S, Hubbard AR, Poole S, Romisch J, Gray E: Antithrombin inhibits lipopolysaccharide-induced tissue factor and interleukin-6 production by mononuclear cells, human umbilical vein endothelial cells, and whole blood. Crit Care Med 2001, 29: 134-139. 10.1097/00003246-200101000-00027CrossRefPubMed
53.
Zurück zum Zitat Gritti D, Malinverno A, Gasparetto C, Wiedermann CJ, Ricevuti R: Attenuation of leukocyte beta 2-integrin expression by antithrombin-III. Int J Immunopathol Pharmacol 2004, 17: 27-32.PubMed Gritti D, Malinverno A, Gasparetto C, Wiedermann CJ, Ricevuti R: Attenuation of leukocyte beta 2-integrin expression by antithrombin-III. Int J Immunopathol Pharmacol 2004, 17: 27-32.PubMed
54.
Zurück zum Zitat Uchiba M, Okajima K, Kaun C, Wojta J, Binder BR: Inhibition of the endothelial cell activation by antithrombin in vitro. Thromb Haemost 2004, 92: 1420-1427.PubMed Uchiba M, Okajima K, Kaun C, Wojta J, Binder BR: Inhibition of the endothelial cell activation by antithrombin in vitro. Thromb Haemost 2004, 92: 1420-1427.PubMed
55.
Zurück zum Zitat Harada N, Okajima K, Yuksel M, Isobe H: Contribution of capsaicin-sensitive sensory neurons to antithrombin-induced reduction of ischemia/reperfusion-induced liver injury in rats. Thromb Haemost 2005, 93: 48-56.PubMed Harada N, Okajima K, Yuksel M, Isobe H: Contribution of capsaicin-sensitive sensory neurons to antithrombin-induced reduction of ischemia/reperfusion-induced liver injury in rats. Thromb Haemost 2005, 93: 48-56.PubMed
56.
Zurück zum Zitat Spannagl M, Hoffmann H, Siebeck M, Weipert J, Schwarz HP, Schramm W: A purified antithrombin III-heparin complex as a potent inhibitor of thrombin in porcine endotoxin shock. Thromb Res 1991, 61: 1-10. 10.1016/0049-3848(91)90163-QCrossRefPubMed Spannagl M, Hoffmann H, Siebeck M, Weipert J, Schwarz HP, Schramm W: A purified antithrombin III-heparin complex as a potent inhibitor of thrombin in porcine endotoxin shock. Thromb Res 1991, 61: 1-10. 10.1016/0049-3848(91)90163-QCrossRefPubMed
57.
Zurück zum Zitat Hoffmann J, Wiedermann CJ, Juers M, Ostermann H, Kienast J, Briegel J, Strauss R, Warren BL, Opal SM: Benefit/risk profile of high-dose antithrombin III in the treatment of severe sepsis without concomitant heparin. Thromb Haemost 2006, in press. Hoffmann J, Wiedermann CJ, Juers M, Ostermann H, Kienast J, Briegel J, Strauss R, Warren BL, Opal SM: Benefit/risk profile of high-dose antithrombin III in the treatment of severe sepsis without concomitant heparin. Thromb Haemost 2006, in press.
58.
Zurück zum Zitat Opal SM, Kessler CM, Roemisch J, Knaub S: Antithrombin, heparin, and heparan sulfate. Crit Care Med 2002, (Suppl):S325-S331. 10.1097/00003246-200205001-00024 Opal SM, Kessler CM, Roemisch J, Knaub S: Antithrombin, heparin, and heparan sulfate. Crit Care Med 2002, (Suppl):S325-S331. 10.1097/00003246-200205001-00024
59.
Zurück zum Zitat Corrigan JJ, Jordan CM: Heparin therapy in septicemia with disseminated intravascular coagulation. N Engl J Med 1970, 283: 778-782.CrossRefPubMed Corrigan JJ, Jordan CM: Heparin therapy in septicemia with disseminated intravascular coagulation. N Engl J Med 1970, 283: 778-782.CrossRefPubMed
60.
Zurück zum Zitat Sleight P: Debate: subgroup analyses in clinical trials: fun to look at but don't believe them! Curr Control Trials Cardiovasc Med 2000, 1: 25-27. 10.1186/CVM-1-1-025PubMedCentralCrossRefPubMed Sleight P: Debate: subgroup analyses in clinical trials: fun to look at but don't believe them! Curr Control Trials Cardiovasc Med 2000, 1: 25-27. 10.1186/CVM-1-1-025PubMedCentralCrossRefPubMed
61.
Zurück zum Zitat Wiedermann CJ, Hoffmann JN, Juers M, Ostermann H, Kienast J, Briegel J, Strauss R, Keinecke HO, Warren BL, Opal SM, for the KyberSept investigators: High-dose antithrombin III in the treatment of severe sepsis with a high risk of death: efficacy and safety. Crit Care Med 2006, 34: 285-292. 10.1097/01.CCM.0000194731.08896.99CrossRefPubMed Wiedermann CJ, Hoffmann JN, Juers M, Ostermann H, Kienast J, Briegel J, Strauss R, Keinecke HO, Warren BL, Opal SM, for the KyberSept investigators: High-dose antithrombin III in the treatment of severe sepsis with a high risk of death: efficacy and safety. Crit Care Med 2006, 34: 285-292. 10.1097/01.CCM.0000194731.08896.99CrossRefPubMed
62.
Zurück zum Zitat van Deventer SJ, Buller HR, ten Cate JW, Aarden LA, Hack CE, Sturk A: Experimental endotoxemia in humans: analysis of cytokine release and coagulation, fibrinolytic, and complement pathways. Blood 1990, 76: 2520-2526.PubMed van Deventer SJ, Buller HR, ten Cate JW, Aarden LA, Hack CE, Sturk A: Experimental endotoxemia in humans: analysis of cytokine release and coagulation, fibrinolytic, and complement pathways. Blood 1990, 76: 2520-2526.PubMed
63.
Zurück zum Zitat van der Poll T, Buller HR, ten Cate H, Wortel CH, Bauer KA, van Deventer SJ, Hack CE, Sauerwein HP, Rosenberg RD, ten Cate JW: Activation of coagulation after administration of tumor necrosis factor to normal subjects. N Engl J Med 1990, 322: 1622-1627.CrossRefPubMed van der Poll T, Buller HR, ten Cate H, Wortel CH, Bauer KA, van Deventer SJ, Hack CE, Sauerwein HP, Rosenberg RD, ten Cate JW: Activation of coagulation after administration of tumor necrosis factor to normal subjects. N Engl J Med 1990, 322: 1622-1627.CrossRefPubMed
64.
Zurück zum Zitat Levi M, ten Cate H, Bauer KA, van der Poll T, Edgington TS, Buller HR, van Deventer SJ, Hack CE, ten Cate JW, Rosenberg RD: Inhibition of endotoxin-induced activation of coagulation and fibrinolysis by pentoxifylline or by a monoclonal anti-tissue factor antibody in chimpanzees. J Clin Invest 1994, 93: 114-120.PubMedCentralCrossRefPubMed Levi M, ten Cate H, Bauer KA, van der Poll T, Edgington TS, Buller HR, van Deventer SJ, Hack CE, ten Cate JW, Rosenberg RD: Inhibition of endotoxin-induced activation of coagulation and fibrinolysis by pentoxifylline or by a monoclonal anti-tissue factor antibody in chimpanzees. J Clin Invest 1994, 93: 114-120.PubMedCentralCrossRefPubMed
65.
Zurück zum Zitat Drake TA, Cheng J, Chang A, Taylor FB Jr: Expression of tissue factor, thrombomodulin, and E-selectin in baboons with lethal Escherichia coli sepsis. Am J Pathol 1993, 142: 1458-1470.PubMedCentralPubMed Drake TA, Cheng J, Chang A, Taylor FB Jr: Expression of tissue factor, thrombomodulin, and E-selectin in baboons with lethal Escherichia coli sepsis. Am J Pathol 1993, 142: 1458-1470.PubMedCentralPubMed
66.
Zurück zum Zitat Nawroth PP, Stern DM: Modulation of endothelial cell hemostatic properties by tumor necrosis factor. J Exp Med 1986, 163: 740-745. 10.1084/jem.163.3.740CrossRefPubMed Nawroth PP, Stern DM: Modulation of endothelial cell hemostatic properties by tumor necrosis factor. J Exp Med 1986, 163: 740-745. 10.1084/jem.163.3.740CrossRefPubMed
67.
Zurück zum Zitat Osterud B, Flaegstad T: Increased tissue thromboplastin activity in monocytes of patients with meningococcal infection: related to an unfavourable prognosis. Thromb Haemost 1983, 49: 5-7.PubMed Osterud B, Flaegstad T: Increased tissue thromboplastin activity in monocytes of patients with meningococcal infection: related to an unfavourable prognosis. Thromb Haemost 1983, 49: 5-7.PubMed
68.
Zurück zum Zitat Martinez MA, Pena JM, Fernandez A, Jimenez M, Juarez S, Madero R, Vazquez JJ: Time course and prognostic significance of hemostatic changes in sepsis: relation to tumor necrosis factor-alpha. Crit Care Med 1999, 27: 1303-1308. 10.1097/00003246-199907000-00017CrossRefPubMed Martinez MA, Pena JM, Fernandez A, Jimenez M, Juarez S, Madero R, Vazquez JJ: Time course and prognostic significance of hemostatic changes in sepsis: relation to tumor necrosis factor-alpha. Crit Care Med 1999, 27: 1303-1308. 10.1097/00003246-199907000-00017CrossRefPubMed
69.
Zurück zum Zitat Feistritzer C, Mosheimer BA, Tancevski I, Kaneider NC, Sturn DH, Patsch JR, Wiedermann CJ: Src tyrosine kinase-dependent migratory effects of antithrombin in leukocytes. Exp Cell Res 2005, 305: 214-220. 10.1016/j.yexcr.2005.01.001CrossRefPubMed Feistritzer C, Mosheimer BA, Tancevski I, Kaneider NC, Sturn DH, Patsch JR, Wiedermann CJ: Src tyrosine kinase-dependent migratory effects of antithrombin in leukocytes. Exp Cell Res 2005, 305: 214-220. 10.1016/j.yexcr.2005.01.001CrossRefPubMed
70.
Zurück zum Zitat Simons M, Horowitz A: Syndecan-4-mediated signalling. Cell Signal 2001, 13: 855-862. 10.1016/S0898-6568(01)00190-5CrossRefPubMed Simons M, Horowitz A: Syndecan-4-mediated signalling. Cell Signal 2001, 13: 855-862. 10.1016/S0898-6568(01)00190-5CrossRefPubMed
71.
Zurück zum Zitat Kaneider NC, Feistritzer C, Gritti D, Mosheimer BA, Ricevuti G, Patsch JR, Wiedermann CJ: Expression and function of syndecan-4 in human platelets. Thromb Haemost 2005, 93: 1120-1127.PubMed Kaneider NC, Feistritzer C, Gritti D, Mosheimer BA, Ricevuti G, Patsch JR, Wiedermann CJ: Expression and function of syndecan-4 in human platelets. Thromb Haemost 2005, 93: 1120-1127.PubMed
72.
Zurück zum Zitat Kienast J, Juers M, Wiedermann CJ, Hoffmann JN, Ostermann H, Briegel J, Strauss R, Warren BL, Opal SM: Treatment effects of high-dose antithrombin III without concomitant heparin in patients with severe sepsis with and without disseminated intravascular coagulation. J Thromb Haemost 2006, 4: 90-97. 10.1111/j.1538-7836.2005.01697.xCrossRefPubMed Kienast J, Juers M, Wiedermann CJ, Hoffmann JN, Ostermann H, Briegel J, Strauss R, Warren BL, Opal SM: Treatment effects of high-dose antithrombin III without concomitant heparin in patients with severe sepsis with and without disseminated intravascular coagulation. J Thromb Haemost 2006, 4: 90-97. 10.1111/j.1538-7836.2005.01697.xCrossRefPubMed
73.
Zurück zum Zitat Kipnis E, Guery BP, Tournoys A, Leroy X, Robriquet L, Fialdes P, Neviere R, Fourrier F: Massive alveolar thrombin activation in Pseudomonas aeruginosa -induced acute lung injury. Shock 2004, 21: 444-451. 10.1097/00024382-200405000-00008CrossRefPubMed Kipnis E, Guery BP, Tournoys A, Leroy X, Robriquet L, Fialdes P, Neviere R, Fourrier F: Massive alveolar thrombin activation in Pseudomonas aeruginosa -induced acute lung injury. Shock 2004, 21: 444-451. 10.1097/00024382-200405000-00008CrossRefPubMed
74.
Zurück zum Zitat Di Micco B, Di Micco P, Lepretti M, Stiuso P, Donnarumma G, Iovene MR, Capasso R, Tufano MA: Hyperproduction of fibrin and inefficacy of antithrombin III and α2 macroglobulin in the presence of bacterial porins. Int J Exp Pathol 2005, 86: 241-245. 10.1111/j.0959-9673.2005.00430.xPubMedCentralCrossRefPubMed Di Micco B, Di Micco P, Lepretti M, Stiuso P, Donnarumma G, Iovene MR, Capasso R, Tufano MA: Hyperproduction of fibrin and inefficacy of antithrombin III and α2 macroglobulin in the presence of bacterial porins. Int J Exp Pathol 2005, 86: 241-245. 10.1111/j.0959-9673.2005.00430.xPubMedCentralCrossRefPubMed
75.
Zurück zum Zitat Edwards AM, Jenkinson HF, Woodward MJ, Dymock D: Binding properties and adhesion-mediating regions of the major sheath protein of Treponema denticola ATCC 35405. Infect Immun 2005, 73: 2891-2898. 10.1128/IAI.73.5.2891-2898.2005PubMedCentralCrossRefPubMed Edwards AM, Jenkinson HF, Woodward MJ, Dymock D: Binding properties and adhesion-mediating regions of the major sheath protein of Treponema denticola ATCC 35405. Infect Immun 2005, 73: 2891-2898. 10.1128/IAI.73.5.2891-2898.2005PubMedCentralCrossRefPubMed
76.
Zurück zum Zitat Masson D, Tschopp J: Inhibition of lymphocyte protease granzyme A by antithrombin III. Mol Immunol 1988, 25: 1283-1289. 10.1016/0161-5890(88)90043-0CrossRefPubMed Masson D, Tschopp J: Inhibition of lymphocyte protease granzyme A by antithrombin III. Mol Immunol 1988, 25: 1283-1289. 10.1016/0161-5890(88)90043-0CrossRefPubMed
77.
Zurück zum Zitat Zeerleder S, Hack CE, Caliezi C, van Mierlo G, Eerenberg-Belmer A, Wolbink A, Wuillenmin WA: Activated cytotoxic T cells and NK cells in severe sepsis and septic shock and their role in multiple organ dysfunction. Clin Immunol 2005, 116: 158-165. 10.1016/j.clim.2005.03.006CrossRefPubMed Zeerleder S, Hack CE, Caliezi C, van Mierlo G, Eerenberg-Belmer A, Wolbink A, Wuillenmin WA: Activated cytotoxic T cells and NK cells in severe sepsis and septic shock and their role in multiple organ dysfunction. Clin Immunol 2005, 116: 158-165. 10.1016/j.clim.2005.03.006CrossRefPubMed
78.
Zurück zum Zitat Wiedermann CJ, Kaneider NC: Comparison of mechanisms after post-hoc analyses of the drotrecogin alfa (activated) and antithrombin III trials in severe sepsis. Ann Med 2004, 36: 194-203. 10.1080/07853890410027943CrossRefPubMed Wiedermann CJ, Kaneider NC: Comparison of mechanisms after post-hoc analyses of the drotrecogin alfa (activated) and antithrombin III trials in severe sepsis. Ann Med 2004, 36: 194-203. 10.1080/07853890410027943CrossRefPubMed
79.
Zurück zum Zitat Kountchev J, Bijuklic K, Bellmann R, Wiedermann CJ, Joannidis M: Reduction of D-dimer levels after therapeutic administration of antithrombin in acquired antithrombin deficiency of severe sepsis. Crit Care 2005, 9: R596-R600. 10.1186/cc3808PubMedCentralCrossRefPubMed Kountchev J, Bijuklic K, Bellmann R, Wiedermann CJ, Joannidis M: Reduction of D-dimer levels after therapeutic administration of antithrombin in acquired antithrombin deficiency of severe sepsis. Crit Care 2005, 9: R596-R600. 10.1186/cc3808PubMedCentralCrossRefPubMed
Metadaten
Titel
Clinical review: Molecular mechanisms underlying the role of antithrombin in sepsis
verfasst von
Christian J Wiedermann
Publikationsdatum
01.02.2006
Verlag
BioMed Central
Erschienen in
Critical Care / Ausgabe 1/2006
Elektronische ISSN: 1364-8535
DOI
https://doi.org/10.1186/cc4822

Weitere Artikel der Ausgabe 1/2006

Critical Care 1/2006 Zur Ausgabe

Update AINS

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.