Thromb Haemost 2007; 98(01): 97-104
DOI: 10.1160/TH07-04-0277
Anniversary Issue Contribution
Schattauer GmbH

Antithrombin – Early prophecies and present challenges

Ulrich Abildgaard
1   Haematological Research Laboratory, Department of Medicine, Aker University Hospital, Oslo, Norway
› Author Affiliations
Further Information

Correspondence to:

Ulrich Abildgaard, MD, PhD
Haematological Research Laboratory
Department of Medicine
Aker University Hospital
0514 Oslo, Norway
Phone: +47 22 89 4883   
Fax: +47 22 89 4259   

Publication History

Received 15 April 2007

Accepted 21 May 2007

Publication Date:
29 November 2017 (online)

 

 


#
  • References

  • 1 Morawitz P. Die Chemie der Blutgerinnung. Ergebn. Pysiol 1905; 4: 307-422.
  • 2 Gasser HS. The significance of prothrombin and of free and combined thromb in inblood-serum. Amer J Physiol 1916; 42: 378-394.
  • 3 Marcum JA. William Henry Howell and Jay McLean: The experimental context for the discovery of heparin. Perspectives in biology and medicine. The University of Chicago. 1990; 33: 214-230.
  • 4 Brinkhous KM, Smith HP, Waner ED. et al. The inhibition of blood clotting: an unidentified substance which acts in conjunction with heparin to prevent the conversion of prothrombin into thrombin. Am J Physiol 1939; 125: 683-687.
  • 5 Quick AJ. The normal antithrombin of the blood and its relation to heparin. Amer J Physiol 1938; 123: 712-719.
  • 6 Fell C, Ivanovic S, Johnson A. et al. Differentiation of plasma antithrombin activities. Proc Soc Exp Biol Med 1954; 85: 199-202.
  • 7 Mosesson M. Update on antithrombin I (fibrin). Thromb Haemost 2007; 98: 105-108.
  • 8 Hensen A, Loeliger EA. Antithrombin III. Its metabolism and its function in blood coagulation. Thromb Diat Haemorrh 1963; 9 (Suppl. 01) 1-84.
  • 9 Egeberg O. Inherited antithrombin deficiency causing thrombophilia. Thromb Diath Haemorrh 1965; 13: 516-530.
  • 10 Godal HC, Abildgaard U. Gelation of fibrin in plasma by ethanol. Scand J Haematol 1966; 3: 342-350.
  • 11 Abildgaard U. N-terminal analysis during coagulation of purified human fibrinogen, fraction I, and plasma. Scand J Clin Lab Invest 1965; 17: 529-536.
  • 12 Abildgaard U. Purification of two progressive antithrombins of human plasma. Scand J Clin Lab Invest 1967; 19: 190-195.
  • 13 Abildgaard U. Inhibition of the thrombin-fibrinogen reaction by antithrombin III, studied by N-terminal analysis. Scand J Clin Lab Invest 1967; 20: 207-216.
  • 14 Abildgaard U. Inhibition of the trombin-fibrinogen reaction by heparin and purifiedc of actor. Scand J Haematol 1968; 5: 440-453.
  • 15 Abildgaard U. Highly purified antithrombin III with heparin cofactor activity prepared by disc electro-phoresis. Scand J Clin Lab Invest 1968; 21: 89-91.
  • 16 Heimburger N. On the proteinase inhibitors of human plasma with special reference to antithrombin. First International Symposium on tissue factors in the homeostasis of the coagulation-fibrinolysis system. Florence 1967. Extracts, Behringwerke, Marburg/Lahn 1967 p. 353-362.
  • 17 Abildgaard U. Binding of thrombin to antithrombin III. Scand J Clin Lab Invest 1969; 24: 23-27.
  • 18 Biggs R, Denson KWE, Akman N. et al. Antithrombin III. anti-factor Xa, and heparin. Br J Haematol 1970; 19: 283-305.
  • 19 Abildgaard U, Egeberg O. Thrombin inhibitoryactivity of fractions obtained by gel filtration of antihrombin III deficient plasma. Scand J Haemat 1968; 5: 155-157.
  • 20 Mann Jr LT, Simonsen M, Jensenius JC, Abildgaard U. Antithrombin III: Protection against death after injection of thomboplastin. Science 1969; 166: 517-518.
  • 21 Fagerhol MK, Abildgaard U. Immunological studies on human antithrombin III. Influence of age, sex and use of oral contraceptives on serum concentration. Scand J Haemat 1970; 7: 10-17.
  • 22 Grimmer Ö, Fagerhol MK. Immunoelectrophoretic quantitation of antithrombin III. Electroimmunodiffusion in agarose gels containing heparin. Int J Peptide Protein Res 1977; 9: 85-90.
  • 23 Abildgaard U, Fagerhol MK, Egeberg O. Comparison of progressive antithrombin activity and the concentrations of three thrombin inhibitors in plasma. Scand J Clin Lab Invest 1970; 26: 349-354.
  • 24 Abildgaard U. Antithrombin and related inhibitors of coagulation. In: Recent advances in blood coagulation, number three. Poller L. editor. Chuchill Livingstone; London: 1981. pp. 151-173.
  • 25 Seegers WH, Cole ER, Harrmison CR. et al. Neutralization of autoprothrombin C activity with anti-thrombin. Can J Biochem 1964; 42: 356-364.
  • 26 Yin ET, Wessler S, Stoll PJ. Rabbit plasma inhibitor of the activated species of blood coagulation factor X: purification and some properties. J Biol Chem 1971; 246: 3694-3702.
  • 27 Rosenberg RD, Damus PS. The purification and mechanism of action of human antithrombin-heparin cofactor. J Biol Chem 1973; 248: 6490-6505.
  • 28 Damus PS, Hicks M, Rosenberg RD. Anticoagulant action of heparin. Nature 1973; 246: 355-357.
  • 29 Kurachi K, Kuchikawa K, Scmer G. et al. Inhibition of bovine factor IXa and factor Xa by antihrombin. Biochemistry 1976; 15: 373-377.
  • 30 Godal HC, Rygh M, Laake K. Progressive inactivation of purified factor VII by heparin and antithrombin III. Thromb Res 1974; 5: 773-775.
  • 31 Boyer C, Wolf JM, Lavergne JM. et al. Thrombin generation and formation of thrombin-antithrombin III complexes in congenital antithrombin III deficiency. Thromb Res 1980; 20: 207-218.
  • 32 Ödegaard OR, Lie M. Simultaneous inactivation of thrombin and factor Xa by AT III: influence of heparin. Thromb Res 1978; 12: 697-800.
  • 33 Marciniak E. Factor Xa inactivation by antithrombin III: Evidence for biological stabilization of factor Xa by Factor V-phospholipid complex. Brit J Haematol 1973; 24: 391.
  • 34 Jesty J. The kinetics of inhibition of α-thrombin in human plasma. J Biol Chem 1986; 261: 10313-10318.
  • 35 Björk I, Jackson CM, Jörnvall H. et al. The active site of antithrombin. Release of the same proteolytically cleaved form of the inhibitor from complexes with factor IXa, factor Xa, and thrombin. J Biol Chem 1982; 257: 2406-2411.
  • 36 Marciniak E. Thrombin-induced proteolysis of human antithrombin III: an outstanding contribution of heparin. Brit J Haematol 1981; 48: 325-336.
  • 37 Seegers WH, Yoshinari M, Landaburu RH. Anti-thrombin as the substrate of the enzyme thrombin. Thromb Diath Haemorrh 1960; 4: 293-298.
  • 38 Miller-Andersson M, Borg H, Andersson LO. Purification of antithrombin III by affinity chromatography. Thromb Res 1974; 5: 439-452.
  • 39 Lindahl U. Heparan sulfate-protein interactions -A concept for drug design?. Thromb Haemost 2007; 98: 109-115.
  • 40 Barrowcliffe TW. LMW heparin: Relationship berween antithrombotic and anticoagulant activities. In: Heparin and related polysaccharides. Advances Exp Med Biol 1992; 313: 205-220.
  • 41 Marciniak E, Gockerman JP. Heparin-induced decrease in circulating antithrombin-III. Lancet 1977; II: 581-584.
  • 42 Blomback M, Bremme K, Hellgren M. et al. Thromboprophylaxis with low molecular mass heparin, “Fragmin” (dalteparin), during pregnancy-a longitudinal study. Blood Coagul Fibrinolysis 1998; 9: 1-9.
  • 43 Carlson TH, Simon TL, Atencio AC. Invivodistribution of human radioionidated antithrombin III: distribution among three physiologic pools. Blood 1985; 66: 13-19.
  • 44 Teien AN, Abildgaard U, Höök M. The anticoagulant effect of heparin sulfate and dermatan sulfate. Thromb Res 1976; 8: 859-867.
  • 45 Knot EAR, de Jong E, ten Cate JW. et al. Purified radiolabeled antithrombin III metabolism in three families with hereditary AT III deficiency: application of athree-compartment model. Blood 1986; 67: 93-98.
  • 46 Preissner KT, Jenne D. Structure of vitronectin and its biological role in haemostasis. Thromb Haemost 1991; 66: 123-132.
  • 47 Wells MJ, Blajchman MA. In vivo clearance of ternary complexes of vitronectin-thrombin-antithrombin is mediated by heparin sulfate proteoglycans. J Biol Chem 1998; 273: 23440-23447.
  • 48 Carrell RW, Huntington JA. How serpins change theirfold for better and for worse. Biochem Soc Symp 2003; 70: 163-178.
  • 49 Sas G, Pepper D, Cash JD. Further investigations on antithrombin III in the plasma of the patients with the abnormality of antithrombin III “Budapest”. Thromb Diath Haemorrh 1975; 33: 564-572.
  • 50 Nagy Losonczy H, Szaksz I. et al. An analysis of clinical and laboratory data in patients with congenital antithrombin III (AT III) deficiency. Acta Med Acad Scient Hung 1979; 36: 53-60.
  • 51 Penner JA, Hassouna H, Hunter MJ. et al. A clinically silent antithrombin III defect in an Ann Arbor family. Thromb Haemost 1979; 186: 186 (Abstract).
  • 52 Tait RC, Walker ID, Perry DJ. et al. Prevalence of antithrombin deficiency in the healthy population. Brit J Haematol 1994; 87: 106-112.
  • 53 Bock SC, Wion KL, Vehar GA. et al. Cloning and expression of the cDNA for human antithrombin III. Nucleic Acid Res 1982; 10: 8113-8125.
  • 54 Lane DA, Bayston T, Olds RJ. et al. Antithrombin mutation database. 2nd (1997) update. Thromb Haemost 1997; 77: 197-211.
  • 55 Javelin L. Prophylactic and therapeutic use of anti-thrombin III concentrates. In: The biology of antithrombins. CRC Press Boca Raton; Florida, USA;: 1979. pp. 115-140.
  • 56 Chamontin B, Guittard J, Laroche M. et al. Traitement d’une thrombose veinuse profonde en presence d’un deficit congenial en anithrombin III. A propos de l’utilisation de concentres purifies. Arch Mal Coer 1984; 77: 1064-1067.
  • 57 Abildgaard U. Relative roles of tissue factor path-way inhibitor and antithrombin in the control of thrombogenesis. Blood Coagul Fibrinol 1995; 6 (Suppl. 01) S45-S49.
  • 58 Hellgren M, Tengborn L, Abildgaard U. Pregnancy in women with congenital antithrombin III deficiency: Experience of treatment with heparin and antithrombin. Gynecol Obst Invest 1982; 14: 127-141.
  • 59 Konkle BA, Bauer KA, Weinstein R. et al. Use of recombinant human antithrombin in patients with congenital antithrombin deficiency undergoing surgical procedures. Transfusion1 2003; 43: 390-394.
  • 60 Mosvold J, Abildgaard R, Jenssen H. et al. Low antithrombin III in acute hepatic failure at term. Scand J Haematol 1982; 29: 48-50.
  • 61 Lasch HG, Rodreguez-Ermann F, Schimpf KL. Antithrombin III und Anti-Blutthrombokinase be iexperimenteller Verbruchskoagulopathie. Klin Wchnschr 1961; 39: 645-647.
  • 62 Blauhut B, Kramar H, Vinazzer H. et al. Substitution of antithrombin III in shock and DIC: A randomised study. Thromb Res 1985; 39: 81-89.
  • 63 Fourrier F, Chopin C, Huart JJ. et al. Double-blind, placebo-controlled trial of antithrobin III coentrates in septic shock with disseminated intravascular coagulation. Chest 1993; 104: 882-888.
  • 64 Jochum M. Influence of high-dose antithrombin concentrate therapy on the release of cellular proteinases, cytokines, and soluble adhesion molecules in acute inflammation. Sem Hematol 1995; 32: 19-32.
  • 65 Mesters RM, Manucci PM, Coppola R. et al. Factor VIIa andantithrombin III activity during severe sepsis and shock in neutropenic patients. Blood 1996; 88: 881-886.
  • 66 Sivula M, Tallgren M, Pettilä V. Moified score for the disseminated intravascular coagulation in the critically ill. Int Care Med 2005; 31: 1209-1214.
  • 67 Niedermayr N, Schramm W, Kamolz L. et al. Anti-thrombin deficiency and its relationship to severe burns. Burns 2007; 33: 173-178.
  • 68 Emerson TE, Fournel MA, Redens TB. et al. Efficacy of antithrombin III supplementation in animal models of fulminant E. coli endotoxinemia or bacteremia. Am J Med 1989; 87 3B 27s-33s.
  • 69 Taylor FB, Emerson Jr TE, Jordan R. et al. Anti-thrombin-III prevents the lethal effects of Escherichia coli infusion in baboons. Circul Shock 1988; 26: 227-235.
  • 70 Minnema MC, Chang ACK, Jansen PM. et al. Recombinant human antithrombin III improves survival and attenuates inflammatory responses in baboons lethally charged with Escherichia coli . Blood 2000; 95: 1117-1123.
  • 71 Levi M, ten Cate H, Van de Poll T. Disseminated intravascular coagulation: State of the art. Thromb Haemost 1999; 82: 695-705.
  • 72 Warren BL, Eid A, Singer P. et al. Caring for the critically ill patient. High-dose antithrombin III in severe sepsis: arandomised controlled trial. J Am Med Assoc 2001; 286: 1869-1878.
  • 73 Kienast J, Juers M, Wiedermann CJ. et al Kyber Cept investigators.. Treatment effects of high dose anti-thrombin without concomitant heparin in patients with severe sepsis with our without disseminated intravascular coagulation. J Thromb Haemost 2006; 4: 90-97.
  • 74 Hoffmann JN, Wiedermann CJ, Juers M. et al. Kyber Cept investigators.. Benefit/risk profile of high-dose antithrombin in patients with severe sepsis treated with and without concomitant heparin. Thromb Haemost 2006; 95: 850-856.
  • 75 Jilma B. Antithrombin for severe sepsis? Try it again, but without heparin. Thromb Haemost 2006; 95: 755.
  • 76 Svensson AM, Whiteley GR, Callas PW. et al. SELDI-TOF plasma profiles distinguish individuals in a protein C-deficient family with thrombotic episodes occurring before age 40. Thromb Haemost 2006; 96: 725-730.

Correspondence to:

Ulrich Abildgaard, MD, PhD
Haematological Research Laboratory
Department of Medicine
Aker University Hospital
0514 Oslo, Norway
Phone: +47 22 89 4883   
Fax: +47 22 89 4259   

  • References

  • 1 Morawitz P. Die Chemie der Blutgerinnung. Ergebn. Pysiol 1905; 4: 307-422.
  • 2 Gasser HS. The significance of prothrombin and of free and combined thromb in inblood-serum. Amer J Physiol 1916; 42: 378-394.
  • 3 Marcum JA. William Henry Howell and Jay McLean: The experimental context for the discovery of heparin. Perspectives in biology and medicine. The University of Chicago. 1990; 33: 214-230.
  • 4 Brinkhous KM, Smith HP, Waner ED. et al. The inhibition of blood clotting: an unidentified substance which acts in conjunction with heparin to prevent the conversion of prothrombin into thrombin. Am J Physiol 1939; 125: 683-687.
  • 5 Quick AJ. The normal antithrombin of the blood and its relation to heparin. Amer J Physiol 1938; 123: 712-719.
  • 6 Fell C, Ivanovic S, Johnson A. et al. Differentiation of plasma antithrombin activities. Proc Soc Exp Biol Med 1954; 85: 199-202.
  • 7 Mosesson M. Update on antithrombin I (fibrin). Thromb Haemost 2007; 98: 105-108.
  • 8 Hensen A, Loeliger EA. Antithrombin III. Its metabolism and its function in blood coagulation. Thromb Diat Haemorrh 1963; 9 (Suppl. 01) 1-84.
  • 9 Egeberg O. Inherited antithrombin deficiency causing thrombophilia. Thromb Diath Haemorrh 1965; 13: 516-530.
  • 10 Godal HC, Abildgaard U. Gelation of fibrin in plasma by ethanol. Scand J Haematol 1966; 3: 342-350.
  • 11 Abildgaard U. N-terminal analysis during coagulation of purified human fibrinogen, fraction I, and plasma. Scand J Clin Lab Invest 1965; 17: 529-536.
  • 12 Abildgaard U. Purification of two progressive antithrombins of human plasma. Scand J Clin Lab Invest 1967; 19: 190-195.
  • 13 Abildgaard U. Inhibition of the thrombin-fibrinogen reaction by antithrombin III, studied by N-terminal analysis. Scand J Clin Lab Invest 1967; 20: 207-216.
  • 14 Abildgaard U. Inhibition of the trombin-fibrinogen reaction by heparin and purifiedc of actor. Scand J Haematol 1968; 5: 440-453.
  • 15 Abildgaard U. Highly purified antithrombin III with heparin cofactor activity prepared by disc electro-phoresis. Scand J Clin Lab Invest 1968; 21: 89-91.
  • 16 Heimburger N. On the proteinase inhibitors of human plasma with special reference to antithrombin. First International Symposium on tissue factors in the homeostasis of the coagulation-fibrinolysis system. Florence 1967. Extracts, Behringwerke, Marburg/Lahn 1967 p. 353-362.
  • 17 Abildgaard U. Binding of thrombin to antithrombin III. Scand J Clin Lab Invest 1969; 24: 23-27.
  • 18 Biggs R, Denson KWE, Akman N. et al. Antithrombin III. anti-factor Xa, and heparin. Br J Haematol 1970; 19: 283-305.
  • 19 Abildgaard U, Egeberg O. Thrombin inhibitoryactivity of fractions obtained by gel filtration of antihrombin III deficient plasma. Scand J Haemat 1968; 5: 155-157.
  • 20 Mann Jr LT, Simonsen M, Jensenius JC, Abildgaard U. Antithrombin III: Protection against death after injection of thomboplastin. Science 1969; 166: 517-518.
  • 21 Fagerhol MK, Abildgaard U. Immunological studies on human antithrombin III. Influence of age, sex and use of oral contraceptives on serum concentration. Scand J Haemat 1970; 7: 10-17.
  • 22 Grimmer Ö, Fagerhol MK. Immunoelectrophoretic quantitation of antithrombin III. Electroimmunodiffusion in agarose gels containing heparin. Int J Peptide Protein Res 1977; 9: 85-90.
  • 23 Abildgaard U, Fagerhol MK, Egeberg O. Comparison of progressive antithrombin activity and the concentrations of three thrombin inhibitors in plasma. Scand J Clin Lab Invest 1970; 26: 349-354.
  • 24 Abildgaard U. Antithrombin and related inhibitors of coagulation. In: Recent advances in blood coagulation, number three. Poller L. editor. Chuchill Livingstone; London: 1981. pp. 151-173.
  • 25 Seegers WH, Cole ER, Harrmison CR. et al. Neutralization of autoprothrombin C activity with anti-thrombin. Can J Biochem 1964; 42: 356-364.
  • 26 Yin ET, Wessler S, Stoll PJ. Rabbit plasma inhibitor of the activated species of blood coagulation factor X: purification and some properties. J Biol Chem 1971; 246: 3694-3702.
  • 27 Rosenberg RD, Damus PS. The purification and mechanism of action of human antithrombin-heparin cofactor. J Biol Chem 1973; 248: 6490-6505.
  • 28 Damus PS, Hicks M, Rosenberg RD. Anticoagulant action of heparin. Nature 1973; 246: 355-357.
  • 29 Kurachi K, Kuchikawa K, Scmer G. et al. Inhibition of bovine factor IXa and factor Xa by antihrombin. Biochemistry 1976; 15: 373-377.
  • 30 Godal HC, Rygh M, Laake K. Progressive inactivation of purified factor VII by heparin and antithrombin III. Thromb Res 1974; 5: 773-775.
  • 31 Boyer C, Wolf JM, Lavergne JM. et al. Thrombin generation and formation of thrombin-antithrombin III complexes in congenital antithrombin III deficiency. Thromb Res 1980; 20: 207-218.
  • 32 Ödegaard OR, Lie M. Simultaneous inactivation of thrombin and factor Xa by AT III: influence of heparin. Thromb Res 1978; 12: 697-800.
  • 33 Marciniak E. Factor Xa inactivation by antithrombin III: Evidence for biological stabilization of factor Xa by Factor V-phospholipid complex. Brit J Haematol 1973; 24: 391.
  • 34 Jesty J. The kinetics of inhibition of α-thrombin in human plasma. J Biol Chem 1986; 261: 10313-10318.
  • 35 Björk I, Jackson CM, Jörnvall H. et al. The active site of antithrombin. Release of the same proteolytically cleaved form of the inhibitor from complexes with factor IXa, factor Xa, and thrombin. J Biol Chem 1982; 257: 2406-2411.
  • 36 Marciniak E. Thrombin-induced proteolysis of human antithrombin III: an outstanding contribution of heparin. Brit J Haematol 1981; 48: 325-336.
  • 37 Seegers WH, Yoshinari M, Landaburu RH. Anti-thrombin as the substrate of the enzyme thrombin. Thromb Diath Haemorrh 1960; 4: 293-298.
  • 38 Miller-Andersson M, Borg H, Andersson LO. Purification of antithrombin III by affinity chromatography. Thromb Res 1974; 5: 439-452.
  • 39 Lindahl U. Heparan sulfate-protein interactions -A concept for drug design?. Thromb Haemost 2007; 98: 109-115.
  • 40 Barrowcliffe TW. LMW heparin: Relationship berween antithrombotic and anticoagulant activities. In: Heparin and related polysaccharides. Advances Exp Med Biol 1992; 313: 205-220.
  • 41 Marciniak E, Gockerman JP. Heparin-induced decrease in circulating antithrombin-III. Lancet 1977; II: 581-584.
  • 42 Blomback M, Bremme K, Hellgren M. et al. Thromboprophylaxis with low molecular mass heparin, “Fragmin” (dalteparin), during pregnancy-a longitudinal study. Blood Coagul Fibrinolysis 1998; 9: 1-9.
  • 43 Carlson TH, Simon TL, Atencio AC. Invivodistribution of human radioionidated antithrombin III: distribution among three physiologic pools. Blood 1985; 66: 13-19.
  • 44 Teien AN, Abildgaard U, Höök M. The anticoagulant effect of heparin sulfate and dermatan sulfate. Thromb Res 1976; 8: 859-867.
  • 45 Knot EAR, de Jong E, ten Cate JW. et al. Purified radiolabeled antithrombin III metabolism in three families with hereditary AT III deficiency: application of athree-compartment model. Blood 1986; 67: 93-98.
  • 46 Preissner KT, Jenne D. Structure of vitronectin and its biological role in haemostasis. Thromb Haemost 1991; 66: 123-132.
  • 47 Wells MJ, Blajchman MA. In vivo clearance of ternary complexes of vitronectin-thrombin-antithrombin is mediated by heparin sulfate proteoglycans. J Biol Chem 1998; 273: 23440-23447.
  • 48 Carrell RW, Huntington JA. How serpins change theirfold for better and for worse. Biochem Soc Symp 2003; 70: 163-178.
  • 49 Sas G, Pepper D, Cash JD. Further investigations on antithrombin III in the plasma of the patients with the abnormality of antithrombin III “Budapest”. Thromb Diath Haemorrh 1975; 33: 564-572.
  • 50 Nagy Losonczy H, Szaksz I. et al. An analysis of clinical and laboratory data in patients with congenital antithrombin III (AT III) deficiency. Acta Med Acad Scient Hung 1979; 36: 53-60.
  • 51 Penner JA, Hassouna H, Hunter MJ. et al. A clinically silent antithrombin III defect in an Ann Arbor family. Thromb Haemost 1979; 186: 186 (Abstract).
  • 52 Tait RC, Walker ID, Perry DJ. et al. Prevalence of antithrombin deficiency in the healthy population. Brit J Haematol 1994; 87: 106-112.
  • 53 Bock SC, Wion KL, Vehar GA. et al. Cloning and expression of the cDNA for human antithrombin III. Nucleic Acid Res 1982; 10: 8113-8125.
  • 54 Lane DA, Bayston T, Olds RJ. et al. Antithrombin mutation database. 2nd (1997) update. Thromb Haemost 1997; 77: 197-211.
  • 55 Javelin L. Prophylactic and therapeutic use of anti-thrombin III concentrates. In: The biology of antithrombins. CRC Press Boca Raton; Florida, USA;: 1979. pp. 115-140.
  • 56 Chamontin B, Guittard J, Laroche M. et al. Traitement d’une thrombose veinuse profonde en presence d’un deficit congenial en anithrombin III. A propos de l’utilisation de concentres purifies. Arch Mal Coer 1984; 77: 1064-1067.
  • 57 Abildgaard U. Relative roles of tissue factor path-way inhibitor and antithrombin in the control of thrombogenesis. Blood Coagul Fibrinol 1995; 6 (Suppl. 01) S45-S49.
  • 58 Hellgren M, Tengborn L, Abildgaard U. Pregnancy in women with congenital antithrombin III deficiency: Experience of treatment with heparin and antithrombin. Gynecol Obst Invest 1982; 14: 127-141.
  • 59 Konkle BA, Bauer KA, Weinstein R. et al. Use of recombinant human antithrombin in patients with congenital antithrombin deficiency undergoing surgical procedures. Transfusion1 2003; 43: 390-394.
  • 60 Mosvold J, Abildgaard R, Jenssen H. et al. Low antithrombin III in acute hepatic failure at term. Scand J Haematol 1982; 29: 48-50.
  • 61 Lasch HG, Rodreguez-Ermann F, Schimpf KL. Antithrombin III und Anti-Blutthrombokinase be iexperimenteller Verbruchskoagulopathie. Klin Wchnschr 1961; 39: 645-647.
  • 62 Blauhut B, Kramar H, Vinazzer H. et al. Substitution of antithrombin III in shock and DIC: A randomised study. Thromb Res 1985; 39: 81-89.
  • 63 Fourrier F, Chopin C, Huart JJ. et al. Double-blind, placebo-controlled trial of antithrobin III coentrates in septic shock with disseminated intravascular coagulation. Chest 1993; 104: 882-888.
  • 64 Jochum M. Influence of high-dose antithrombin concentrate therapy on the release of cellular proteinases, cytokines, and soluble adhesion molecules in acute inflammation. Sem Hematol 1995; 32: 19-32.
  • 65 Mesters RM, Manucci PM, Coppola R. et al. Factor VIIa andantithrombin III activity during severe sepsis and shock in neutropenic patients. Blood 1996; 88: 881-886.
  • 66 Sivula M, Tallgren M, Pettilä V. Moified score for the disseminated intravascular coagulation in the critically ill. Int Care Med 2005; 31: 1209-1214.
  • 67 Niedermayr N, Schramm W, Kamolz L. et al. Anti-thrombin deficiency and its relationship to severe burns. Burns 2007; 33: 173-178.
  • 68 Emerson TE, Fournel MA, Redens TB. et al. Efficacy of antithrombin III supplementation in animal models of fulminant E. coli endotoxinemia or bacteremia. Am J Med 1989; 87 3B 27s-33s.
  • 69 Taylor FB, Emerson Jr TE, Jordan R. et al. Anti-thrombin-III prevents the lethal effects of Escherichia coli infusion in baboons. Circul Shock 1988; 26: 227-235.
  • 70 Minnema MC, Chang ACK, Jansen PM. et al. Recombinant human antithrombin III improves survival and attenuates inflammatory responses in baboons lethally charged with Escherichia coli . Blood 2000; 95: 1117-1123.
  • 71 Levi M, ten Cate H, Van de Poll T. Disseminated intravascular coagulation: State of the art. Thromb Haemost 1999; 82: 695-705.
  • 72 Warren BL, Eid A, Singer P. et al. Caring for the critically ill patient. High-dose antithrombin III in severe sepsis: arandomised controlled trial. J Am Med Assoc 2001; 286: 1869-1878.
  • 73 Kienast J, Juers M, Wiedermann CJ. et al Kyber Cept investigators.. Treatment effects of high dose anti-thrombin without concomitant heparin in patients with severe sepsis with our without disseminated intravascular coagulation. J Thromb Haemost 2006; 4: 90-97.
  • 74 Hoffmann JN, Wiedermann CJ, Juers M. et al. Kyber Cept investigators.. Benefit/risk profile of high-dose antithrombin in patients with severe sepsis treated with and without concomitant heparin. Thromb Haemost 2006; 95: 850-856.
  • 75 Jilma B. Antithrombin for severe sepsis? Try it again, but without heparin. Thromb Haemost 2006; 95: 755.
  • 76 Svensson AM, Whiteley GR, Callas PW. et al. SELDI-TOF plasma profiles distinguish individuals in a protein C-deficient family with thrombotic episodes occurring before age 40. Thromb Haemost 2006; 96: 725-730.