Advertisement

Regulation and Control of the Fibrinolytic System

  • H. Roger Lijnen
  • Désiré Collen
Part of the NATO ASI Series book series (NSSA, volume 191)

Abstract

Mammalian blood contains an enzymatic system, called the fibrinolytic system, that is capable of dissolving blood clots. This system comprises an inactive proenzyme, plasminogen, which can be converted to the active enzyme plasmin, that will degrade fibrin into soluble fibrin degradation products. Two immunologically distinct types of physiological plasminogen activators have been identified: the tissue-type plasminogen activator (t-PA) and the urokinase-type plasminogen activator (u-PA). Inhibition of the fibrinolytic system may occur either at the level of the plasminogen activators, by plasminogen activator inhibitors (PAI-1 and PAI-2), or at the level of plasmin, mainly by α2-antiplasmin. Plasminogen activation may also be induced by an “intrinsic” pathway involving several proteins such as Factor XII, high molecular weight kininogen (HMWK) and prekallikrein.

Keywords

Plasminogen Activator Deep Vein Thrombosis Plasminogen Activator Inhibitor Fibrinolytic System Plasminogen Activation 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    L. Sottrup-Jensen, T.E. Petersen, and S. Magnusson, in: “Atlas of protein sequence and structure”, vol. 5, Suppl. 3, M.O. Dayhoff, ed. National Biomedical Research Foundation, Washington DC, 91 (1978).Google Scholar
  2. 2.
    D. Collen, and H.R. Lijnen, The fibrinolytic system in man. CRC Crit. Rev. Hemat. Onc. 4: 249 (1986).CrossRefGoogle Scholar
  3. 3.
    M. Forsgren, B. Raden, M. Israelsson, et al., Molecular cloning and characterization of a full-length cDNA clone for human plasminogen. FEBS Lett. 213: 254 (1987).CrossRefPubMedGoogle Scholar
  4. 4.
    J.C. Murray, K.H. Buetow, M. Donovan, et al., Linkage disequilibrium of plasminogen polymorphisms and assignment of the gene to human chromosome 6q26–6q27. Am. J. Hum. Genet. 40: 338 (1987).Google Scholar
  5. 5.
    K.C. Robbins, L. Summaria, B. Hsieh, and R.J. Shah, The peptide chains of human plasmin. Mechanism of activation of human plasminogen to plasmin. J. Biol. Chem. 242: 2333 (1967).Google Scholar
  6. 6.
    P. Holvoet, H.R. Lijnen, and D. Collen, A monoclonal antibody specific for Lys-plasminogen. Application to the study of the activation pathways of plasminogen in vivo. J. Biol. Chem. 260: 12106 (1985).Google Scholar
  7. 7.
    D. Collen, On the regulation and control of fibrinolysis. Thromb. Haemost. 43: 77 (1980).Google Scholar
  8. 8.
    B. Wiman, and D. Collen, Molecular mechanism of physiological fibrinolysis. Nature (London) 272: 549 (1978).CrossRefGoogle Scholar
  9. 9.
    E.G. Levine, and D.J. Loskutoff, Cultured bovine endothelial cells produce both urokinase and tissue-type plasminogen activators. J. Cell Biol. 94: 631 (1982).Google Scholar
  10. 10.
    D.C. Rijken, I. Juhan-Vague, F. De Cock, and D. Collen, Measurement of human tissue-type plasminogen activator by a two-site immunoradiometric assay. J. Lab. Clin. Med. 101: 274 (1983).Google Scholar
  11. 11.
    D. Collen, D.C. Rijken, J. Van Damme, and A. Billiau, Purification of human tissue-type plasminogen activator in centigram quantities from human melanoma cell culture fluid and its conditioning for use in vivo. Thromb. Haemost. 48: 294 (1982).PubMedGoogle Scholar
  12. 12.
    D. Pennica, W.E. Holmes, W.J. Kohr, et al., Cloning and expression of human tissue-type plasminogen activator cDNA in E. coll. Nature 301: 214 (1983).CrossRefPubMedGoogle Scholar
  13. 13.
    L. Banyai, A. Varadi, and L. Patthy, Common evolutionary origin of the fibrin-binding structures of fibronectin and tissue-type plasminogen activator. FEBS Lett. 163: 37 (1983).CrossRefPubMedGoogle Scholar
  14. 14.
    A.J. van Zonneveld, H. Veerman, and H. Pannekoek, Autonomous functions of structural domains on human tissue-type plasminogen activator. Proc. Natl. Acad. Sci. USA 83: 4670 (1986).CrossRefPubMedGoogle Scholar
  15. 15.
    J.H. Verheijen, M.P.M. Caspers; G.T.G. Chang, et al., Involvement of forger domain and kringle 2 domain of tissue-type plasminogen activator in fibrin binding and stimulation of activity by fibrin. EMBO J. 5: 3525 (1986).PubMedGoogle Scholar
  16. 16.
    A.J. van Zonneveld, H. Veerman, and H. Pannekoek, On the interaction of the finger and kringle-2 domain of tissue-type plasminogen activator with fibrin. J. Biol. Chem. 261: 14214 (1986).Google Scholar
  17. 17.
    M. Hoylaerts, D.C. Rijken, H.R. Lijnen, and D. Collen, Kinetics of the activation of plasminogen by human tissue plasminogen activator. Role of fibrin. J. Biol. Chem. 257: 2912 (1982).Google Scholar
  18. 18.
    W. Nieuwenhuizen, M. Voskuilen, A. Vermond, et al., The influence of fibrin(ogen) fragments on the kinetic parameters of the tissue-type plasminogen-activator-mediated activation of different forms of plasminogen. Fur. J. Biochem. 174: 163 (1988).Google Scholar
  19. 19.
    M. Rânby, N. Bergsdorf, B. Norrman, et al., Tissue plasminogen activator kinetics, in: “Progress in Fibrinolysis”, vol. 6, Davidson, Bachmann, Bouvier and Kruithof, eds., Churchill Livingstone, Edinburgh, 182 (1983).Google Scholar
  20. 20.
    D.C. Rijken, M. Hoylaerts, and D. Collen, Fibrinolytic properties of one-chain and two-chain human extrinsic (tissue-type) plasminogen activator. J. Biol. Chem. 257: 2920 (1982).Google Scholar
  21. 21.
    G.R. Larsen, K. Henson, and Y. Blue, Variants of human tissue-type plasminogen activator. Fibrin binding, fibrinolytic, and fibrinogenolytic characterization of genetic variants lacking the fibronectin finger-like and/or the epidermal growth factor domains. J. Biol. Chem. 263: 1023 (1988).PubMedGoogle Scholar
  22. 22.
    M.-J. Gething, B. Adler, J.-A. Boose, et al., Variants of human tissue-type plasminogen activator that lack specific structural domains of the heavy chain. EMBO J. 7: 2731 (1988).Google Scholar
  23. 23.
    B. Rajput, S.F. Degen, E. Reich, et al., Chromosomal locations of human tissue plasminogen activator and urokinase genes. Science 230: 672 (1985).CrossRefPubMedGoogle Scholar
  24. 24.
    M.J. Browne, A.W.R. Tyrrell, C.G. Chapman, et al., Isolation of a human tissue-type plasminogen activator genomic DNA clone and its expression in mouse L cells. Gene 33: 279 (1985).CrossRefPubMedGoogle Scholar
  25. 25.
    S.J.F. Degen, B. Rajput, and E. Reich, The human tissue plasminogen activator gene. J. Biol. Chem. 261: 6972 (1986).Google Scholar
  26. 26.
    T. Ny, F. Elgh, and B. Lund, The structure of the human tissue-type plasminogen activator gene: correlation of intron and exon structures to functional and structural domains. Proc. Natl. Acad. Sci. USA 81: 5355 (1984).Google Scholar
  27. 27.
    L. Patthy, Evolution of the proteases of blood coagulation and fibrinolysis by assembly from modules. Cell 41: 657 (1985).CrossRefPubMedGoogle Scholar
  28. 28.
    H. Pannekoek, C. de Vries, and A.J. van Zonneveld, Mutants of human tissue-type plasminogen activator (t-PA): structural aspects and functional properties. Fibrinolysis 2: 123 (1988).Google Scholar
  29. 29.
    H.R. Lijnen, D.C. Stump, and D. Collen, Single-chain urokinase-type plasminogen activator: mechanism of action and thrombolytic properties. Sem. Thromb. Hemost. 13: 152 (1987).Google Scholar
  30. 30.
    W.E. Holmes, D. Pennica, M. Blaber, et al., Cloning and expression of the gene for pro-urokinase in Escherichia coll. Biotechnology 3: 923 (1985).CrossRefGoogle Scholar
  31. 31.
    G.J. Steffens, W. Günzler, F. Ötting, et al., The complete amino acid sequence of low molecular mass urokinse from human urine. Hoppe-Seyler’Z. Physiol. Chem. 363: 1043 (1982).Google Scholar
  32. 32.
    A. Riccio, G. Grimaldi, P. Verde, et al., The human urokinase-plasminogen activator gene and its promoter. Nucleic Acids Res. 13: 2759 (1985).CrossRefPubMedGoogle Scholar
  33. 33.
    H.R. Lijnen, B. Van Hoef, F. De Cock, and D. Collen, On the mechanisms of plasminogen activation and fibrin dissolution by single chain urokinase-type plasminogen activator (scu-PA) in a plasma milieu in vitro. Blood 73: 1864 (1989).PubMedGoogle Scholar
  34. 34.
    V. Ellis, M.F. Scully, and V V Kakkar, Plasminogen activation by single-chain urokinase in functional isolation. A kinetic study. J. Biol. Chem. 262: 14998 (1987).Google Scholar
  35. 35.
    L.C. Petersen, L.R. Lund, L.S. Nielsen, et al., One-chain urokinase-type plasminogen activator from human sarcoma cells is a proenzyme with little or no intrinsic activity. J. Biol. Chem. 263: 11189 (1988).PubMedGoogle Scholar
  36. 36.
    W.E. Holmes, L. Nelles, H.R. Lijnen, and D. Collen, Primary structure of human a2-antiplasmin, a serine protease inhibitor (serpin). J. Biol. Chem. 262: 1659 (1987).PubMedGoogle Scholar
  37. 37.
    H.R. Lijnen, W.E. Holmes, B. Van Hoef, et al., Amino-acid sequence of human a2-antiplasmin. Eur. J. Biochem. 166: 565 (1987).Google Scholar
  38. 38.
    H.R. Lijnen, B. Wiman, and D. Collen, Partial primary structure of human a2-antiplasmin. Homology with other plasma protease inhibitors. Thromb. Haemost. 48: 311 (1982).Google Scholar
  39. 39.
    B. Wiman, and D. Collen, Purification and characterization of human antiplasmin, the fast-acting plasmin inhibitor in plasma. Eur. J. Biochem. 78: 19 (1977).Google Scholar
  40. 40.
    B. Wiman, and D. Collen, On the kinetics of the reaction between human antiplasmin and plasmin. Eur. J. Biochem. 84: 573 (1978).Google Scholar
  41. 41.
    E.K.O. Kruithof, Plasminogen activator inhibitors. A review. Enzyme 40: 113 (1988).Google Scholar
  42. 42.
    T. Ny, M. Sawdey, D.A. Lawrence, et al., Cloning and sequence of a cDNA coding for the human J9-migrating endothelial cell-type plasminogen activator inhibitor. Proc. Natl. Acad. Sci. USA 83: 6776 (1986).Google Scholar
  43. 43.
    H. Pannekoek, H. Veerman, H. Lambers, et al., Endothelial plasminogen activator inhibitor (PAI): a new member of the serpin gene family. EMBO J. 5: 2539 (1986).PubMedGoogle Scholar
  44. 44.
    K.W. Klinger, R. Winqvist, A. Riccio, et al., Plasminogen activator inhibitor type 1 gene is located at region q21.3-q22 of chromosome 7 and genetically linked with cystic fibrosis. Proc. Natl. Acad. Sci. USA 84: 8548 (1987).Google Scholar
  45. 45.
    E.K.O. Kruithof, A. Gudinchet, and F. Bachmann, Plasminogen activator inhibitor 1 and plasminogen activator inhibitor 2 in various disease states. Thromb. Haemost. 59: 7 (1988).Google Scholar
  46. 46.
    M. Colucci, JA. Paramo, and D. Collen, Generation in plasma of a fast-acting inhibitor of plasminogen activator in response to endotoxin stimulation. J. Clin. Invest. 75: 818 (1985).Google Scholar
  47. 47.
    P.J. Declerck, M. De Mol, M.C. Alessi, et al., Purification and characterization of a plasminogen activator inhibitor-1 binding protein from human plasma. Identification as a multimeric form of S protein (Vitronectin). J. Biol. Chem. 263: 15454 (1988).PubMedGoogle Scholar
  48. 48.
    E.K.O. Kruithof, C. Tran-Thang, A. Ransijn, and F. Bachmann, Demonstration of a fast-acting inhibitor of plasminogen activators in human plasma. Blood 64: 907 (1984).PubMedGoogle Scholar
  49. 49.
    E.K.O. Kruithof, G. Nicoloso, and F. Bachmann, Measurement of plasminogen activator inhibitor 1: development of a radioimmunoassay and observations on its plasma concentration during venous occlusion and after platelet aggregation. Blood 70: 1645 (1987).PubMedGoogle Scholar
  50. 50.
    C.M. Hekman, and D. Loskutoff, Endothelial cells produce a latent inhibitor of plasminogen activators that can be activated by denaturants. J. Biol. Chem. 260: 11581 (1985).Google Scholar
  51. 51.
    B. Wiman, and P. Wallen, The specific interaction between plasminogen and fibrin. A physiological role of the lysine binding site in plasminogen. Thromb. Res. 10: 213 (1977).Google Scholar
  52. 52.
    C. Tran-Thang, P. Wyss, E.K.O. Kruithof, et al., Tissue-type plasminogen activator increases the binding of plasminogen to clots. Haemostasis 14: 17 (Abstract) (1984).Google Scholar
  53. 53.
    H.R. Lijnen, C. Zamarron, M. Blaber, et al., Activation of plasminogen by pro-urokinase. I. Mechanism. J. Biol. Chem. 261: 1253 (1986).Google Scholar
  54. 54.
    B. Wiman, H.R. Lijnen, and D. Collen, On the specific interaction between the lysine-binding sites in plasmin and complementary sites in a2-antiplasmin and in fibrinogen. Biochim. Biophys. Acta 579: 142 (1979).Google Scholar
  55. 55.
    A. Ichinose, T. Tamaki, and N. N. Aoki, Factor XIII-mediated cross-linking of N}{2-terminal peptide of a2-plasmin inhibitor to fibrin. FEBS Lett. 153: 369 (1983).CrossRefPubMedGoogle Scholar
  56. 56.
    D.L. Higgins, and GA. Vehar, Interaction of one-chain and two-chain tissue plasminogen activator with intact and plasmin-degraded fibrin. Biochemistry 26: 7786 (1987).CrossRefPubMedGoogle Scholar
  57. 57.
    R. Pannell, J. Black, and V. Gurewich, Complementary modes of action of tissue-type plasminogen activator and pro-urokinase by which their synergistic effect on clot lysis may be explained. J. Clin. Invest. 81: 853 (1988).Google Scholar
  58. 58.
    N. Aoki, H. Saito, T. Kamiya, et al., Congenital deficiency of a2-plasmin inhibitor associated with severe hemorrhagic tendency. J. Clin. Invest. 63: 877 (1979).Google Scholar
  59. 59.
    C. Kluft, E. Vellenga, E.J.P. Brommer, and G. Wijngaards, A familial hemorrhagic diathesis in a Dutch family: an inherited deficiency of a2-antiplasmin. Blood 59: 1169 (1982).PubMedGoogle Scholar
  60. 60.
    C. Kluft, E. Vellenga, and E.J.P. Brommer, Homozygous a2-antiplasmin deficiency. Lancet 2: 206 (1979).CrossRefPubMedGoogle Scholar
  61. 61.
    K. Koie, K. Ogata, T. Kamiya, et al., 112-plasmin inhibitor deficiency (Miyasato disease). Lancet 2: 1334 (1978).CrossRefPubMedGoogle Scholar
  62. 62.
    H. Stormorken, G.O. Gogstad, and F. Brosstad, Hereditary a2-antiplasmin deficiency. Thromb. Res. 31: 647 (1983).Google Scholar
  63. 63.
    A. Yoshioka, H. Kamitsuji, T. Takase, et al., Congenital deficiency of a2-plasmin inhibitor in three sisters. Haemostasis 11: 176 (1982).PubMedGoogle Scholar
  64. 64.
    LA. Miles, E.F. Plow, K.J. Donnelly, et al., A bleeding disorder due to deficiency of a2-antiplasmin. Blood 59: 1246 (1982).PubMedGoogle Scholar
  65. 65.
    D. Collen, H. Bounameaux, F. De Cock, et al., Analysis of coagulation and fibrinolysis during intravenous infusion of recombinant human tissue-type plasminogen activator in patients with acute myocardial infarction. Circulation 73: 511 (1986).CrossRefPubMedGoogle Scholar
  66. 66.
    H.K. Nieuwenhuis, C. Kluft, G. Wijngaards, et aL, a2-Antiplasmin Enschede: an autosomal recessive hemorrhagic disorder caused by a dysfunctional a2-antiplasmin molecule. Thromb. Haemost. 50: 170 (abstract 528 ) (1983).Google Scholar
  67. 67.
    W.E. Holmes, H.R. Lijnen, L. Nelles, et al., a2-Antiplasmin Enschede• alanine insertion and abolition of plasmin inhibitory activity. Science 238: 209 (1987).CrossRefPubMedGoogle Scholar
  68. 68.
    NA. Booth, B. Bennett; G. Wijngaards, and J.H.K. Grieve, A new life-long hemorrhagic disorder due to excess plasminogen activator. Blood 61: 267 (1983).PubMedGoogle Scholar
  69. 69.
    J. Aznar, A. Estellés, V. Villa, et al., Inherited fibrinolytic disorder due to an enhanced plasminogen activator level. Thromb. Haemost. 52: 196 (1984).Google Scholar
  70. 70.
    J. Mehta, P. Mehta, D. Lawson, and T. Saldeen, Plasma tissue plasminogen activator inhibitor levels in coronary artery disease: correlation with age and serum triglyceride concentrations. J. Am. Coll. Cardiol. 9: 263 (1987).Google Scholar
  71. 71.
    JA. Pâramo, M. Colucci, and D. Collen, Plasminogen activator inhibitor in the blood of patients with coronary artery disease. Br. Med. J. 291: 573 (1985).Google Scholar
  72. 72.
    L.-0. Ahnér, and H. Ohlin, Elevated levels of the rapid inhibitor of plasminogen activator in acute myocardial infarction. Thromb. Res. 47: 335 (1987).CrossRefGoogle Scholar
  73. 73.
    F.WA. Verheugt, J.W. ten Cate, A. Sturk, et al., Tissue plasminogen activator activity and inhibition in acute myocardial infarction and angiographically normal coronary arteries. Am. J. Cardiol. 59: 1075 (1987).Google Scholar
  74. 74.
    A. Hamsten, M. Blombäck, B. Wiman, et al., Haemostatic function in myocardial infarction. Br. Heart J. 55: 58 (1986).Google Scholar
  75. 75.
    A. Hamsten, B. Wiman, U. De Faire, and M. Blombäck, Increased plasma levels of a rapid inhibitor of tissue plasminogen activator in young survivors of myocardial infarction. N. Engl. J. Med. 213: 1557 (1985).Google Scholar
  76. 76.
    A. Hamsten, U. De Faire, G. Walldius, et al., Plasminogen activator inhibitor in plasma; risk factor for recurrent myocardial infarction. Lancet ii: 3 (1987).Google Scholar
  77. 77.
    I. Juhan-Vague, B. Moerman, F. De Cock, et al., Plasma levels of a specific inhibitor of tissue-type plasminogen activator (and urokinase) in normal and pathological conditions. Thromb. Res. 33: 523 (1984).Google Scholar
  78. 78.
    B. Wiman, and J. Chmielewska, A novel fast inhibitor to tissue plasminogen activator in plasma, which may be of great pathophysiological significance. Scand. J. Clin. Lab. Invest. 45 (Suppl 177): 43 (1985).Google Scholar
  79. 79.
    C. Kluft, A.F.H. Jie, G.D.O. Lowe, et al., Association between postoperative hyper-response in t-PA inhibition and deep vein thrombosis. Thromb. Haemost. 56: 107 (1986).Google Scholar
  80. 80.
    G. Mellbring, S. Dahlgren, B. Wiman, and O. Sunnegâardh, Relationship between preoperative status of the fibrinolytic system and occurrence of deep vein thrombosis after major abdominal surgery. Thromb. Res. 39: 157 (1985).Google Scholar
  81. 81.
    JA. Pâramo, M.J. Alfaro, and E. Rocha, Postoperative changes in the plasmatic levels of tissue-type plasminogen activator and its fast-acting inhibitors. Relationship to deep vein thrombosis and influence of prophylaxis. Thromb. Haemost. 54: 713 (1985).Google Scholar
  82. 82.
    G. Mellbring, S. Dahlgren, and B. Wiman, Plasma fibrinolytic activity in patients undergoing major abdominal surgery. Acta Chir. Scand. 151: 109 (1985).Google Scholar
  83. 83.
    M. Jorgensen, and V. Bonnevie-Nielsen, Increased concentration of the fast-acting plasminogen activator inhibitor in plasma associated with familial venous thrombosis. Br. J. Haemat. 65: 175 (1987).Google Scholar
  84. 84.
    I. Juhan-Vague, J. Valadier, M.C. Alessi, et al., Deficient t-PA release and elevated PA inhibitor levels in patients with spontaneous or recurrent deep vein thrombosis. Thromb. Haemost. 57: 67 (1987).Google Scholar
  85. 85.
    M. Stalder, J. Hauert, E.K.O. Kruithof, and F. Bachmann, Release of vascular plasminogen activator (v-PA) after venous stasis: electrophoretic-zymographic analysis of free and complexed v-PA. Br. J. Haemat. 61: 169 (1985).Google Scholar
  86. 86.
    G. Mellbring, S. Dahlgren, S. Reiz, and B. Wiman, Fibrinolytic activity in plasma and deep vein thrombosis after major abdominal surgery. Thromb. Res. 32: 575 (1983).Google Scholar
  87. 87.
    A. Girolami, F. Marafioti, M. Rubertelli, and M.G. Cappellato, Congenital heterozygous plasminogen deficiency associated with a severe thrombotic tendency. Acta Haemat. 75: 54 (1986).CrossRefPubMedGoogle Scholar
  88. 88.
    D.K. Hasegawa, B.J. Tyler, and J.R. Edson, Thrombotic disease in three families with inherited plasminogen deficiency. Blood 60: 213 (1982).Google Scholar
  89. 89.
    R. Lottenberg, F.R. Dolly, and C.S. Kitchens, Recurring thromboembolic disease and pulmonary hypertension associated with severe hypoplasminogenemia. Am. J. Hematol. 19: 181 (1985).Google Scholar
  90. 90.
    P.M. Mannucci, C. Kluft, D.W. Traas, et al., Congenital plasminogen deficiency associated with venous thromboembolism: therapeutic trial with stanozolol. Br. J. Haemat. 63: 753 (1986).Google Scholar
  91. 91.
    J.W. ten Cate, M. Peters, and H. Buller, Isolated plasminogen deficiency in a patient with recurrent thromboembolic complications. Thromb. Haemost. 50: 59 (Abstract) (1983).Google Scholar
  92. 92.
    R.D. Davis, and R.C. Picoff, Low plasminogen levels and liver disease. Am. J. Clin. Path. 59: 175 (1969).Google Scholar
  93. 93.
    L.C. Kordich, V.P. Porterie, O. Lago, et al., Mini-plasminogen like molecule in septic patients. Thromb. Res. 47: 553 (1987).Google Scholar
  94. 94.
    M. Verstraete, J. Vermylen, and D. Collen, Intravascular coagulation in liver disease. Ann. Rev. Med. 25: 447 (1974).Google Scholar
  95. 95.
    M. Kazama, C. Tahara, Z. Suzuki, et al., Abnormal plasminogen, a case of recurrent thrombosis. Thromb. Res. 21: 517 (1981).Google Scholar
  96. 96.
    T. Miyata, S. Iwanaga, Y. Sakata, et al., Plasminogens Tochigi II and Nagoya: two additional molecular defects with Ala60° Thr replacement found in plasmin light chain variants. J. Biochem. 96: 277 (1984).Google Scholar
  97. 97.
    T. Miyata, S. Iwanaga, Y. Sakata, and N. Aoki, Plasminogen Tochigi: inactive plasmin resulting from replacement of alanine-600 by threonine in the active site. Proc. Natl. Acad. Sci. USA 79: 6132 (1982).Google Scholar
  98. 98.
    J. Soria, C. Soria, O. Bertrand, et al., Plasminogen Paris I: congenital abnormal plasminogen and its incidence in thrombosis. Thromb. Res. 32: 229 (1983).Google Scholar
  99. 99.
    R.C. Wohl, L. Summaria, J. Chediak, et al., Human plasminogen variant Chicago III. Thromb. Haemost. 48: 146 (1982).Google Scholar
  100. 100.
    R.C. Wohl, L. Summaria, and K.C. Robbins, Physiological activation of the human fibrinolytic system. Isolation and characterization of human plasminogen variants, Chicago I and Chicago H. J. Biol. Chem. 254: 9063 (1979).Google Scholar
  101. 101.
    S. Isacson, and I.M. Nilsson, Defective fibrinolysis in blood and vein walls in recurrent “idiopathic” venous thrombosis. Acta Chir. Scand. 138: 313 (1972).Google Scholar
  102. 102.
    C. Korninger, K. Lechner, H. Niessner, et al., Impaired fibrinolytic capacity predisposes for recurrence of venous thrombosis. Thromb. Haemost. 52: 127 (1984).Google Scholar
  103. 103.
    I.M. Nilsson, H. Ljungner, and L. Tengborn, Two different mechanisms in patients with venous thrombosis and defective fibrinolysis: low concentration of plasminogen activator or increased concentration of plasminogen activator inhibitor. Br. Med. J. 290: 1453 (1985).PubMedGoogle Scholar

Copyright information

© Plenum Press, New York 1990

Authors and Affiliations

  • H. Roger Lijnen
    • 1
  • Désiré Collen
    • 1
  1. 1.Center for Thrombosis and Vascular ResearchCampus Gasthuisberg, O & NLeuvenBelgium

Personalised recommendations