Thrombolytic agents - An updated overview

Fibrinolysis and Proteolysis

Volumn 12, Issue SUPPL. 2, 1998, Pages 39-58

  Gulba, D C ^a   Bode, C ^b   Runge, M S ^c   Huber, K ^d  

^a HUMBOLDT UNIVERSITY   (Germany)

^b UNIVERSITY OF HEIDELBERG   (Germany)

^c University of Texas Medical Branch School of Medicine   (United States)

^d UNIVERSITY HOSPITAL INNSBRUCK   (Austria)

Author keywords

[No Author keywords available]

Indexed keywords

ALTEPLASE; ANISTREPLASE; FIBRINOLYTIC AGENT; PLASMINOGEN ACTIVATOR INHIBITOR; RETEPLASE; STAPHYLOKINASE; STREPTOKINASE; TISSUE PLASMINOGEN ACTIVATOR; UROKINASE;

ACUTE HEART INFARCTION; BLOOD CLOT LYSIS; CONFERENCE PAPER; CORONARY ARTERY BLOOD FLOW; DERIVATIZATION; DRUG EFFECT; DRUG POTENCY; ENZYME ACTIVITY; HUMAN; HUMAN CELL; PRIORITY JOURNAL; PROTEIN DEGRADATION; THROMBOEMBOLISM;

EID: 0031734905     PISSN: 13690191     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0268-9499(98)80306-8     Document Type: Conference Paper

References (245)

1. Tillett W S, Sherry S. The effect in patients of streptococcal fibrinolysin (streptokinase) and streptococcal desoxyribonuclease on fibrous, purulent and sanguinous pleural exudations. J Clin Invest 1949; 28: 173-190.
2. DeWood M A, Spores J, Nortske R, Mouser L T, Burroghs R, Golden M S, Lang H T. Prevalence of total coronary occlusion during early hours of transmural myocardial infarction. N Engl J Med 1980; 303: 897-902.
3. Reimer K A, Lowe J E, Rasmussen M M, Jennings R B. The wavefront phenomenon of ischemic cell death. I. myocardial infarct size vs. duration of coronary occlusion in dogs. Circulation 1977; 56: 786-794.
4. Lijnen H R, de Wreede K, Demarsin E, Collen D. Biological and thrombolytic properties of proenzyme and active forms of human urokinase - IV. Variability in fibrinolytic response of plasma of several mammalian species. Thromb Haemost 1984; 52: 31-33.
5. Zamarron C, Lijnen H R, van Hoef B, Collen D. Biological and thrombolytic properties of proenzyme and active forms of human urokinase. I. Fibrinolytic and fibrinogenolytic properties in human plasma in vitro of urokinases obtained from human urine or by recombinant DNA technology. Thromb Haemost 1984; 52: 19-23.
6. Collen D, Stassen J M, Blaber M, Winkler M, Verstraete M. Biological and thrombolytic properties of proenzyme and active forms of human urokinase. III. Thrombolytic properties of natural and recombinant urokinase in rabbits with experimental jugular vein thrombosis. Thromb Haemost 1984; 52: 27-30.
7. Pennica D, Holmes W E, Kohr W, et al. Cloning and expression of human tissue-type plasminogen activator cDNA in E. coli. Nature 1983; 301: 214-221.
8. Brogden R N, Speight T M, Avery G S. Streptokinase: a review of its clinical pharmacology, mechanism of action and therapeutic uses. Drugs 1973; 5: 357-445.
9. de Renzo E C, Siiteri P K, Hutchings B L, Behl P H. Preparations and certain properties of highly purified streptokinase. J Biol Chem 1967; 137: 533-542.
10. Müllertz S, Lasen M. An activator system in blood indispensable for the formation of plasmin by streptokinase. Proc Soc Exper Biol Med 1953; 82: 264-268.
11. McClintock D K, Bell PH. The mechanism of action of human plasminogen by streptokinase. Biochem Biophys Res Commun 1971; 43: 694-702.
12. Cederholm-Williams S A, de Cook F, Lijnen H R, Collen D. Kinetics of the reactions between streptokinase, plasmin and alpha-2-antiplasmin. Eur J Biochem 1979; 100: 125-132.
13. Marder V J, Sherry S. Thrombolytic therapy: current status (first of two parts). N Engl J Med 1988; 318: 1512-1520.
14. Marder V J, Sherry S. Thrombolytic therapy: current status (second of two parts). N Engl J Med 1988; 318: 1585-1595.
15. Barthels M, Gulba D, Engel M J. Systemic fibrinolysis as an effect of intracoronary thrombolysis. In: Davidson J F, Donati M B, Cocchieri S (eds). Progress in Fibrinolysis VII. Edinburgh, Churchill Livingstone, 1985: 49-51.
16. Fletcher A P, Alkjaersig N, Sherry S. The clearance of heterologous protein from the circulation of normal and immunized man. J Clin Invest 1959; 37: 1306-1315.
17. Marder V J. Pharmacology of thrombolytic agents: implications for therapy of coronary artery thrombosis. Circulation 1983; 68 suppl. I: I-2-1-5.
18. Sharma G V R K, Cella G, Parisi A F, Sasahara A A. Thrombolytic therapy. N Engl J Med 1982; 306: 1268-1276.
19. Fletcher A P, Alkjaersig N, Fisher S, Sherry S. The proteolysis of fibrinogen by plasmin: the identification of thrombin-clottable fibrinogen derivatives which polymerize abnormally. J Lab Clin Med 1966; 68: 780-802.
20. Fletcher A P, Alkjaersig N, Sherry S. Pathogenesis of the coagulation defect developing during pathological plasma proteolytic ("fibrinolytic") states. I. The significance of fibrinogen proteolysis and circulating fibrinogen breakdown products. J Clin Invest 1962; 41: 896-916.
21. Anonick P K, Wolf B B, Gonias S L. Regulation of plasmin, miniplasmnin, and streptokinase-plasmin complex by alpha-2-antiplasmin, alpha-2-macroglobulin, and antithrombin III in the presence of heparin. Thromb Res 1990; 59: 449-462.
22. Bachmann F. Fibrinolysis. In: Verstraete M, Vermylen J, Lijnen R, Arnout J (eds). Thrombosis and Haemostasis 1987 Leuven, University Press, 1987: 227-265.
23. Collen D. On the regulation and control of fibrinolysis. Thromb Haemost 1980; 43: 77-89.
24. Wiman B, Collen D. On the role of alpha-2-antiplasmin in the regulation of fibrinolysis. In: Collen D, Wiman B, Verstraete M (eds). The Physiological Inhibitors of Coagulation and Fibrinolysis. North Holland, Elsevier, 1979: 17-185.
25. Harpel P C. Human alpha-2-macroglobulin. Methods Enzymol 1976; 45: 639-652.
26. Râkôczi I, Wiman B, Collen D. On the biological significance of the specific interaction between fibrin, plasminogen and antiplasmin. Biochim Biophys Acta 1978; 540: 295-300.
27. Thorsen S. Differences in the binding to fibrin of native plasminogen and plasminogen modified by proteolytic degradation. Influence of omega-amino-caboxylic acids. Biochim Biophys Acta 1975; 30: 55-65.
28. Thorsen S, Kok P, Astrup T. Reversible and irreversible alterations of human plasminogen indicated by changes in susceptibility to plasminogen activators and in response to epsilon-aminocaproic acid. Thromb Diath Haemorrh 1974; 32: 325-340.
29. Harpel P C, Chang T-S, Verderber E. Tissue-plasminogen activator and urokinase mediate the binding of glu-plasminogen to plasma fibrin. I. Evidence for new binding sites in plasmin-degraded fibrin. J Biol Chem 1985; 260: 4432-4440.
30. Sherry S. Thrombolytic therapy in acute myocardial infarction. A perspective. Drugs 1987; 33 suppl. 3: 1-12.
31. Schröder R, Biamino G, von Leitner E R, Brügemann T, Heitz J, Vöhringer H F, Wegscheider K. Intravenous shortterm infusion of streptokinase in acute myocardial infarction. Circulation 1983; 67: 536-548.
32. Theiss W, Baumann G, Klein G. Fibrinolytische Behandlung der tiefen Venenthrombosen mit Streptokinase in ultrahoher Dosierung. Dtsch Med Wschr 1987; 112: 668-674.
33. Wun T-C, Schleuning W-D, Reich E. Isolation and characterization of urokinase from human plasma. J Biol Chem 1982; 257: 3276-3283.
34. Collen D, de Cook F, Lijnen H R. Biological and thrombolytic properties of proenzyme and active forms of human urokinase. II. Turnover of natural and recombinant urokinase in rabbits and squirrel monkeys. Thromb Haemost 1984; 52: 24-26.
35. Darras V, Thienpont M, Stump D C, Collen D. Measurement of urokinase-type plasminogen activator (u-PA) with an enzyme-linked immunosorbent asay (ELISA) based on three murine monoclonal antibodies. Thromb Haemost 1986; 56: 411-414.
36. Günzler W, Steffens G, Getting F, Buse G, Flohé L. Structural relationship between human high and low molecular weight mass urokinase. Hoppe-Seyler's Z Physiol Chem 1982; 363: 133-141.
37. Straszburger W, Wollmer A, Pits J E, Glover I D, Tickle I J, Blundell T E, Steffens G J, Günzler W A, Oettinger F, Flohé L. Adaption of plasminogen activator sequences to known protease structures. FEBS Lett 1983; 257: 219-223.
38. Wiman B, Collen D. Molecular mechanism of physiological fibrinolysis. Nature 1978; 272: 549-550.
39. Holmes W E, Pennica D, Blaber M, Rey M W, Guenzler W A, Steffens G J, Heyneker H L. Cloning and expression of the gene of pro-urokinase in Escherichia coli. Biotechnology 1985; 3: 923-929.
40. Barlow G H, Lazer L, Rueter A, Tribby I. Production of plasminogen activators by tissue culture techniques. In: Paoletti R, Sherry S (eds). Thrombosis and Urokinase. New York, Academic Press, 1977: 758.
41. Günzler W A, Cramer J, Frankus E, et al. Chemical, enzymological and pharmacological equivalence of urokinase isolated from genetically transformed bacteria and human urine. Arzneim-Forsch 1985; 35: 652-662.
42. Husain S S, Gurewich V, Lipinski B. Purification and partial characterization of a single-chain-high-molecular-weight form of urokinase from human urine. Arch Biochem Biophys 1982; 220: 31-38.
43. Ploug J, Kjeldgaard N O. Urokinase: an activator of plasminogen from human urine. I. Isolation and properties. Biochim Biophys Acta 1957; 24: 278-282.
44. Wallén P. Activation of plasminogen with urokinase and tissue activator. In: Paoletti R, Sherry S (eds). Thrombosis and Urokinase. London, Academic Press, 1977: 91-102.
45. Robbins V C. The plasminogen-plasmin enzyme system. In: Haemostasis and Thrombosis. London, J.B. Lippincott, 1987: 340-357
46. Constantinides P. Plaque fissure in human coronary thrombosis. J Artheroscl Res 1966; 6: 1-17.
47. D'Angelo A, Mannuci P M. Outcome of treatment of deep-vein thrombosis with urokinase: relationship to dosage, duration of therapy, age of the thrombus and laboratory changes. Thromb Haemost 1984; 51: 236-239.
48. Frey D L. Hemodynamic forces in artherogenesis. In: Scheinberg P (ed). Cerebrovascular Disease. Tenth Princeton Conference. New York, Raven Press, 1976: 77-95.
49. Goldhaber S Z, Kessler C M, Heit J, et al. Randomised controlled trial of recombinant tissue plasminogen activator versus urokinase in the treatment of acute pulmonary embolism. Lancet 1988; II: 293-298.
50. Neuhaus K L, Tebbe U, Gottwik M, et al. Intravenous recombinant tissue plasminogen activator (rt-PA) and urokinase in acute myocardial infarction: results of the German activator urokinase study (GAUS).JACC 1988; 12: 581-587
51. van de Loo JCW, Kriessmann A, Trübestein G, et al. Controlled multicenter pilot study of urokinase-heparin and streptokinase in deep vein thrombosis. Thromb Haemost 1983; 50: 660-663.
52. Suenson E, Petersen L C. Fibrin and plasminogen structures essential to stimulation of plasmin formation by tissue-type plasminogen activator. Biochim Biophys Acta 1986; 870: 510-519.
53. Tran-Thang C, Kruithof E K O, Atkinson J, Bachmann F. High-affinity binding sites for human gluplasminogen unveiled by limited plasmic degradation of human fibrin. Eur J Biochem 1986; 160: 599-604.
54. Tran-Thang C, Kruithof E K O, Bachmann F. Tissue-type plasminogen activator increases the binding of Glu-plasminogen to clots. J Clin Invest 1984; 74: 2009-2016.
55. Collen D, Zamarron C, Lijnen H R, Hoylaerts M. Activation of plasminogen by pro-urokinase. II. Kinetics. J Biol Chem 1986; 261: 1259-1266.
56. Stump D C, Thienpont M, Collen D. Urokinase-related proteins in human urine. Isolation and characterization of single-chain urokinase (pro-urokinase) and urokinase-inhibitor complex. J Biol Chem 1986; 261: 1267-1273.
57. Fletcher A P, Alkjaersig N, Sherry S, Genton E, Hirsh J, Bachmann F. The development of urokinase as a thrombolytic agent: maintenance of a sustained thrombolytic state in man by its intravenous infusion. J Lab Clin Med 1965; 65: 713-731.
58. Köhler M, Sen S, Hermes R, et al. Pharmacokinetics of single-chain urokinase-type plasminogen activator (scu-PA) and two-chain urokinase-type plasminogen activator (tcu-PA) in patients with acute myocardial infarction. Ann Haematol 1991; 62 suppl. A: A75(Abstract).
59. Gulba D C, Lichtlen P R. Urokinasetherapie bei thromboembolischen Erkrankungen. In: Kirchhof B, Kienast J (eds). Thrombolysetherapie. Daten und Argumente für verschiedene Verfahren und Substanzen. Emmendingen, Kesselring, 1988: 45-72.
60. UPET-Study Group: Urokinase pulmonary embolism trial: phase I: a cooperative study (UPET). J Am Med Assoc 1970; 214: 2163-2168.
61. The Urokinase-Streptokinase Pulmonary Embolism Trial Study Group. The Urokinase-Streptokinase Pulmonary Embolism Trial. Phase 2 results. A cooperative study. J Am Med Assoc 1974; 229: 1606-1613.
62. Goldhaber S Z, Kessler C M, Heit J A, et al. t-PA vs. urokinase in acute pulmonary embolism: a randomized controlled trial. Circulation 1991; 84, suppl. II: 357.
63. Smith RAG, Dupe R J, English P D, Green J. Fibrinolysis with acyl-enzymes: new approach to thrombolytic therapy. Nature 1981; 290: 505-508.
64. Bode C, Matsueda G, Hui K Y, Haber E. Antibody directed urokinase - a fibrin specific agent. Science 1985; 230: 765-767.
65. Renkin J, Col-de Beys C, Lavenne-Pardonge E, Pintens H, Col J. analysis of coagulation and fibrinolysis after intravenous anisoylated plasminogen streptokinase activator complex or heparin in patients with acute myocardial infarction. A Belgian multicenter study. Drugs 1987; 33: 253-260.
66. Wiman B, Wallén P. Structural relationship between "glutamic acid" and "lysine" forms of human plasminogen and their interaction with the NH2- terminal activation peptide as studied by affinity chromatography. Eur J Biochem 1975; 50: 489-494.
67. Wallén P, Wiman B. Characterization of human plasminogen. I. On the relationship between different molecular forms of plasminogen demonstrated in plasma and found in purified preparations. Biochim Biophys Acta 1970; 221: 20-30.
68. Wallén P, Wiman B. Characterization of human plasminogen. II. Separation and partial characterization of different molecular forms of human plasminogen. Biochem Biophys Acta 1972; 257: 122-134.
69. Smith RAG, Dupe R J, English P D, Green J. Acyl-enzymes as thrombolytic agents in a rabbit model of venous thrombosis. Thromb Haemost 1982; 47: 269-274.
70. Stainforth D H, Smith RAG, Hibbs M. Streptokinase and anisoylated streptokinase plasminogen complex. Their action on haemostasis in human volunteers. Eur J Pharmacol 1983; 24:751-756.
71. Staniforth D H, Smith RAG, Hibbs M. Streptokinase and anisoylated streptokinase plasminogen complex: their action on hemostasis in human volunteers. Eur J Clin Pharmacol 1983; 24: 751-756.
72. Kasper W, Meinertz T, Wollschläger H, et al. Coronary thrombolysis during acute myocardial infarction by intravenous B R L 26921, a new anisoylated plasminogen-streptokinase activator complex. Am J Cardiol 1986; 58: 418-421.
73. Matsuo O, Rijken D C, Collen D. Comparison of the relative fibrinogenolytic, fibrinolytic and thrombolytic properties of tissue plasminogen activator and urokinase in vitro. Thromb Haemost 1981; 45: 225-229.
74. Fears R, Green J, Smith RAG, Walker P. Induction of a sustained fibrinolytic response by B R L 26921 in vitro. Thromb Res 1985; 38: 251-260.
75. Dupe R J, Green J, Smith RAG. Acylated derivatives of streptokinase-plasminogen activator complex as thrombolytic agents in a dog model of aged venous thrombosis. Thromb Haemost 1985; 53: 56-59.
76. Brochier M L, Quillet L, Kulbertus H, Materne P, Letac B, Cribier A, Monas J P, Sacrez A, Favier J P. Intravenous anisoylated plasminogen streptokinase activator complex versus intravenous streptokinase in evolving myocardial infarction. Primary data from a randomized multicentre study. Drugs 1987; 33 (suppl. 3): 140-145.
77. Brügemann J, van der Meer J, Takens B H, Hillege H, Lie K I. A systemic non-lytic state and local thrombolytic failure of antistreplase (anisoylated plasminogen streptokinase activator complex, APSAC) in acute myocardial infarction. Br Heart J 1990; 64: 355-358.
78. ISIS-3 (Third International Study of Infarct Survival) Collaborative Group: ISIS-3: a randomised comparison of streptokinase vs tissue plasminogen activator vs anistreplase and of aspirin plus heparin vs aspirin alone among 41299 cases of suspected acute infarction. Lancet 1993; 339: 753-770.
79. Karsch K R, Hofmann M, Rentrop K P, Schaper W. Thrombolysis in acute experimental myocardial infarction. JACC 1983; 1:427-435.
80. Bigger jr. J T. Risk stratification after myocardial infarction. Z Kardiol 1985; 74 suppl. 6: 147-157.
81. AIMS Trial Study Group. Effect of intravenous APSAC on mortality after acute myocardial infarction: Preliminary report of a placebo-controlled trial. Lancet 1988; 1: 545-549.
82. Neuberger M S, Williams G T, Fox R O. Recombinant antibodies posessing novel effector functions. Nature 1984; 312: 604-608.
83. Williams G T, Neuberger M S. Production of antibody-tagged enzymes by melanoma cells: application to DNA polymerase I Klenow fragment. Gene 1986; 43: 319-324.
84. Bode C, Kübler W. Antikörper vermittelte Thrombolyse. Klin Wschr 1989; 67: 651-658.
85. Love T W, Runge M S, Haber E. Recombinant antibodies posessing novel effector functions. Methods Enzymol 1989; 178: 515-527.
86. Bode C, Meinhardt G, Runge M S, Nordt T, Freitag M, Arens M, Kûbler W, Haber E. Platelet-targetet fibrinolysis enhances clot lysis and inhibits platelet aggregation. Circulation 1991; 84: 805-813.
87. Haber E. New fibrinolytic agents - future developments. Fibrinolysis 1995; 9 suppl. 1: 100-103.
88. Rijken D C, Collen D. Purification and characterization of the plasminogen activator secreted by human melanoma cells in culture. J Biol Chem 1981; 256: 7035-7041.
89. Ny T, Elgh F, Lund B. The structure of human tissue-type plasminogen activator gene: correlation of intron and exon structures to functional and structural domains. Proc Natl Acad Sci USA 1984; 81: 5355-5359.
90. Brone M J, Dodd I, Carey J E, Chapman C G, Robinson J H. Increased yield of human tissue-type plasminogen activator obtained by means of recombinant DNA technology. Thromb Haemost 1985; 54: 422-424.
91. Rijken D C, Hoylaerts M, Collen D. Fibrinolytic properties of one-chain and two-chain human extrinsic (tissue-type) plasminogen activator. J Biol Chem 1982; 257: 2920-2925.
92. Kok P, Astrup T. Isolation and purification of a tissue plasminogen activator and its comparison with urokinase. Biochemistry 1969; 8: 79-86.
93. Aoki N, von Kaulla K N. The extraction of vascular plasminogen activator from human cadavers and description of some of its properties. Am J Clin Pathol 1971; 55: 171-179.
94. Cole E R, Bachmann F W. Purification and properties of a plasminogen activator from pig heart. J Biol Chem 1977; 252: 3729-3737
95. Collen D, Rijken D C, van Damme J, Billiau A. 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 1982; 48: 294-296.
96. Radcliffe R, Heinze T. Isolation of plasminogen activator from human plasma by chromatography on lysine-Sepharose. Arch Biochem Biophys 1978; 189: 185-194.
97. Wallén P, Kok P, Ranby M. The tissue activator of plasminogen. In: Magnusson S, Ottesen M, Foltman B, Dano K, Neurath H (eds). Regulatory Enzymes and Their Control. Oxford, Pergamon Press, 1978: 127-135.
98. Martin U, Fischer S, Kohnert U, Rudolph R, Sponer G, Stern A, Strein K: Coronary thrombolytic properties of a novel recombinant plasminogen activator (BM 06.022) in a canine model. J Cardiovasc Pharmacol 1991; 18, No 1: 111-119.
99. Christophodoulides M, Boucher D W. The potency of tissue-type plasminogen activator (TPA) determined with chromogen and clot lysis assay. Biologicals 1990; 18: 103-111.
100. Hoylaerts M, Rijken D C, Lijnen H R, Collen D. Kinetics of the activation of plasminogen by human tissue plasminogen activator. Role of fibrin. J Biol Chem 1982; 257: 2912-2919.
101. Norrman B, Wallén P, Ranby M. Fibrinolysis mediated by tissue plasminogen activator. Disclosure of a kinetic transition. Eur J Biochem 1985; 149: 193-200.
102. Kohnert U, Rudolph R, Verheijen J H, et al. Biochemical properties of the kringle 2 and protease domains are maintained in the refolded t-PA deletion variant BM 06.022. Protein Engineering 1992; 5: 93-100.
103. Paoni N F, Keyt B A, Refino C J, et al. A slow clearing, fibrin-specific, PAI resistant variant of t-PA (T103N, KHRR 296-299 AAAA). Thromb Haemost 1993; 70: 307-312.
104. Zamarron C, Lijnen H R, Collen D. Kinetics of the activation of plasminogen by natural and recombinant tissue-type plasminogen activator. J Biol Chem 1983; 259: 2080-2083.
105. Bringmann P, Gruber D, Liese A, Toschi L, Krätzschmar J, Schleuning W-D, Donner P. Structural features mediating fibrin selectivity of vampir bat plasminogen activator. J Biol Chem 1995; 270: 25596-25603.
106. Kingston I B, Castro M J M, Andersonb S. In vitro stimulation of tissue-type plasminogen activator by Alzheimer amyloid b-peptide analogues. Nature Med 1995; 1: 138-142.
107. Sobel B A, Nachowiak D A, Fry E T A, Bergmann S R, Torr S R. Paradoxical attenuation of fibrinolysis attributable to "plasminogen steal" an its implication for coronary thrombolysis. Coron Artery Dis 1990; 1: 111-119.
108. Verstraete M, Bounameaux H, de Cock F, van de Werf F, Collen D. Pharmakokinetics and systemic fibrinogenolytic effects of recombinant human tissue-type plasminogen activator (rt-PA) in humans. J Pharmacol Exp Ther 1985; 235: 506-512.
109. Verstraete M, Su C A P F, Tanswell P, Feuerer W, Collen D. Pharamcokinetics and effects on fibrinolytic and coagulation parameters of two doses of recombinant tissue-type plasminogen activator (rt-PA) in healthy volunteers. Thromb Haemost 1986; 56: 1-5.
110. Tanswell P, Tebbe U, Neuhaus K L, Gläsle-Schwarz L, Wojcik J, Seifried E. Pharmacokinetics and fibrin specificity of alteplase during accelerated infusions in acute myocardial infarction. J Am Coll Cardiol 1992; 19: 1071-1075.
111. Lijnen H R, Marafino B J, Collen D. In vitro flbrinolytic activity of recombinant tissue-type plasminogen activator in the plasma of various primate species. Thromb Haemost 1984; 52: 308-310.
112. Matsuo O, Bando H, Okada K, Tanaka K, Tsukada M, Iga Y, Arimura H. Thrombolytic effect of single-chain pro-urokinase in a rabbit jugular vein thrombosis model. Thromb Res 1986; 42: 187-194.
113. Matsuo O, Rijken D C, Collen D. Thrombolysis by human tissue plasminogen activator and urokinase in rabbits with experimental pulmonary embolus. Nature 1981; 291: 590-591.
114. Korninger G, Matsuo O, Suy R, Stassen J M, Collen D. Thrombolysis with human extrinsic (tissue-type) plasminogen activator in dogs with femoral thrombosis. J Clin Invest 1982; 69: 573-580.
115. Collen D, Stassen J M, Verstraete M. Thrombolysis with human extrinsic (tissue-type) plasminogen activator in rabbits with experimental jugular vein thrombosis. Effect of molecular form and dose of activator, age of the thrombus, and route of administration. J Clin Invest 1982; 71: 368-376.
116. Bergmann S R, Fox A A, Ter-Pogossian M M, Sobel B E, Collen D. Clot-selective coronary thrombolysis with tissue-type plasminogen activator Science 1983; 220: 1181-1183.
117. Neuhaus K-L, von Essen R, Tebbe U, et al. Improved thrombolysis in acute myocardial infarction with front-loaded administration of alteplase: results of the rt-PA-APSAC patency study (TAPS). JACC 1991; 19:885-891.
118. Neuhaus K-L, Feuerer W, Jeep-Tebbe S, Niederer W, Vogt A, Tebbe U. Improved thrombolysis with a modified dose regimen of recombinant tissue-type plasminogen activator. JACC 1989; 14: 1566-1569.
119. The GUSTO Angiographic Investigators. The effect of tissue plasminogen activator, streptokinase, or both on coronary-artery patency, ventricular function, and survival after acute myocardial infarction. N Engl J Med 1993; 329: 1615-1622.
120. The GUSTO Investigators. An International randomized trial comparing four thrombolytic strategies for acute myocardial infarction. N Engl J Med 1993; 329: 673-682.
121. Bode C, Schönermark S, Schuler G, Zimmermann R, Schwarz F, Kübler W. Efficacy of intravenous pro-urokinase and a combination of pro-urokinae and urokinase in acute myocardial infarction. Am J Cardiol 1988; 61: 971-974.
122. Rijken D C, Wijngaards G, Collen D. Tissue-type plasminogen activator from human tissue and cell cultures and its occurance in plasma. In: Collen D, Lijnen H R, Verstraete M (eds). Thrombolysis, Biological and Therapeutic Properties of New Thrombolytic Agents. Edinburgh, Churchill Livingstone, 1985: 15-30.
123. Purvis J A, McNeill A J, Siddiqui R A, et al. Efficacy of 100 mg of double-bolus alteplase in achieving complete perfusion in the treatment of acute myocardial infarction. J Am Coll Cardiol 1994; 23: 6-10.
124. Tranchesi B, Chamone D F, Cobbaert C, van de Werf F, Vanhove P, Verstraete M. Coronary recanalization rate after intravenous bolus of alteplase in acute myocardial infarction. Am J Cardiol 1991; 68: 161-165.
125. Tebbe U, Tanswell P, Seifried E, Feuerer W, Scholz K H, Herrmann K S. Single-bolus injection of recombinant tissue-type plasminogen activator in acute myocardial infarction. Am J Cardiol 1989; 64: 448-453.
126. Tranchesi B, Verstraete M, Vanhove P, van de Werf F, Chamone D F, Belotti G, Pileggi F. Intravenous bolus administration of recombinant tissue plasminogen activator to patients with acute myocardial infarction. Coron Artery Dis 1990; 1: 83-86.
127. Gulba D C, Tanswell P, Dechend R, et al. Sixty minutes alteplase protocol: a new accelerated recombinant tissue-type plasminogen activator regimen for thrombolysis in acute myocardial infarction. J Am Coll Cardiol 1997; 30: 1611-1617.
128. Bleich S D, Adgey A A J, Pickering E, et al. An angiographic assessment of the efficacy and safety of front-loaded and bolus regimens of activase (alteplase, recombinant). The double-bolus lytic efficacy trial (the DOUBLE trial). Circulation 1995; 92 suppl.: 1-415 (Abstract)
129. The Continuous Infusion versus Double-Bolus Administration of Alteplase (COBALT) Investigators. A comparison of continuous infusion of alteplase with double-bolus administration for acute myocardial infarction. N Engl J Med 1997; 337: 1124-1130.
130. Goldhaber S Z, Haire W D, Feldstein M L, et al. Alteplase versus heparin in acute pulmonary embolism: randomised trial assessing right-ventricular function and pulmonary perfusion. The Lancet 1993; 341: 507-511.
131. Goldhaber S Z, Elliot C G, Heiselman W R, Parker J A, Feldstein M L, Sharma G V R K, Nage J S. Recombinant tissue-type plasminogen activator versus a novel dosing regimen of urokinase in acute pulmonary embolism: a randomized controlled multicenter trial. JACC 1992; 20: 24-30.
132. Meyer G, Sors H, Charbonnier B, et al. Effects of intravenous urokinase versus alteplase on total pulmonary resistance in acute massive pulmonary embolism. A European multicenter double-blind trial. JACC 1992; 19: 239-245.
133. Verstraete M, Miller G A H, Bounameaux H, et al. Intravenous and intrapulmonary recombinant tisue-type plasminogen activator in the treatment of acute massive pulmonary embolism. Circulation 1988; 77: 353-360.
134. Gulba D C, Schmid C, Borst H-G, Lichtlen P, Dietz R, Luft F C. Medical compared with surgical treatment for massive pulmonary embolism. Lancet 1994; 343: 576-577.
135. Konstantinides S, Geibel A, Olschewski M, et al. Association between thrombolytic treatment and the prognosis of hemodynamically stable patients with major pulmonary embolism: results of a multicenter registry. Circulation 1997; 96: 882-888.
136. Topol E J, Califf R M, George B S, et al. Coronary arterial thrombolysis with combined infusion of recombinant tissue-type plasminogen activator and urokinase in patients with acute myocardial infarction. Circulation 1988; 77: 1100-1107.
137. Baron A, Loirand G, Pacaud P, Mironneau C, Mironneau J. Dual effect of thrombin on voltage-dependent Ca 2+ channels of portal vein smooth muscle cells. Circ Res 1993; 72: 1317-1325.
138. Eisenberg P R, Sobel B E, Jaffe A S. Characterization in vivo of the fibrin specificity of activators of the fibrinolytic system. Circulation 1988; 78: 592-597.
139. Smalling R W, Schumacher R, Morris D, et al. Improved infarct-related arterial patency after high dose, weight adjusted, rapid infusion of tissue-type plasminogen activator in myocardial infarction: results of a multicenter randomized trial of two dosage regimens. J Am Coll Cardiol 1990; 15: 915-921.
140. Topol E J, George B S, Kereiakes D J, et al. Comparison of two dose regimens of intravenous tissue plasminogen activator for acute myocardial infarction. Am J Cardiol 1988; 61: 723-728.
141. Schmitt M, Jänicke F, Graeff H. Tumor-associated proteases. Fibrinolysis 1992; 6 suppl. 4: 3-26.
142. Moscatelli D M, Rifkin D B. Membrane and matrix localization of proteases: a common theme in tumor invasion and angiogenesis. Biochim Biophys Acta 1988; 948: 67-85.
143. Saskela O, Montesano R. Cell-associated plasminogen activation: regulation and physiological functions. Ann Rev Cell Biol 1988; 4: 93-126.
144. Pepper M S, Montesano R. Proteolytic balance and capillary morphogenesis. Cell Diff Dev 1991; 32: 319-328.
145. Dano K, Andraesen P A, Grondal-Hansen J, Kristensen P, Nielsen L S, Skriver L. Plasminogen activators, tissue degradation and cancer. Adv Cane Res 1985; 44: 139-239.
146. Wun T-C, Ossowski L, Reich E. A proenzyme form of human urokinase. J Biol Chem 1982; 257: 7262-7268.
147. Flohé L, Steffens G J, Günzler W A, et al. Insight into biosynthesis of human urokinase forms. In: Davidson J F, Donati M B, Cocchieri S (eds). Progress in Fibrinolysis VII. Edinburgh, Churchill Livingstone, 1985: 213-216.
148. Steffens G J, Günzler W A, Hennies H-H, et al. Molecular characterization of human low molecular mass urokinase obtained from recombinant E. coli bacteria. In: Davidson J F, Donati M B, Cocchieri S (eds). Progress in Fibrinolysis VII. Edinburgh, Churchill Livingstone, 1985: 217-220.
149. Binnema D J, Dooijewaard G, Turion P N C. An analysis of the activators of single-chain urokinase-type plasminogen activator (scu-PA) in the dextran sulphate euglobulin fraction of normal plasma and of plasmas deficient in factor XII and prekallikrein. Thromb Haemost 1991; 65: 144-148.
150. Gurewich V, Pannell R, Louie S, Kelley P, Suddith R L, Greenlee R. Effective and fibrin-specific clot lysis by a zymogen precursor form of urokinase (pro-urokinase). A study in vitro and in two animal species. J Clin Invest 1984; 73: 1731-1739.
151. Lijnen H R, Collen D. Stimulation by heparin of the plasmin mediated conversion of single-chain to two-chain urokinase type plasminogen activator. Thromb Res 1986; 43: 687-690.
152. Ichinose A, Fujikawa K, Suyama T. The activation of prourokinase by plasma kallikrein and its inactivation by thrombin. J Biol Chem 1986; 261: 3486-3489.
153. Gurewich V, Pannell R. Inactivation of single-chain urokinase (pro-urokinase) by thrombin and thrombin-like enzymes: relevance of the findings to the interpretation of fibrin-binding experiments. Blood 1987; 67: 769-772.
154. Lijnen H R, van Hoef B, Collen D. Activation by plasmin of two-chain urokinase-type plasminogen activator derived from single-chain urokinase-type plasminogen activator by treatment with thrombin. Eur J Biol Chem 1987; 169: 359-364.
155. Schmitt M, Kanayama N, Henschen A, et al. Elastase released from human granulocytes stimulated with N-formyl-chemotactic peptide prevents activation of tumor cell prourokinase (pro-uPA). FEBS Lett 1989; 255: 83-88.
156. Lijnen H R, van Hoef B, Collen D. Comperative kinetic analysis of the activation of human plasminogen by natural and recombinant single-chain urokinase-type plasminogen activator. Biochim Biophys Acta 1986; 884: 402-408.
157. Stump D C, Stassen J M, Demarsin E, Collen D. Comperative thrombolytic properties of single-chain forms of urokinase-type plasminogen activator. Blood 1987; 69: 592-596.
158. van de Werf F, Jang I K, Collen D. Thrombolysis with recombinant human single-chain urokinase-type plasminogen activator (rscu-PA): dose-response in dogs with coronary thrombosis. J Cardiovasc Pharmacol 1987; 9: 91-93.
159. Pannell R, Gurewich V. Pro-urokinase: a study of its stability in plasma and of a mechanism of selective fibrinolytic effect. Blood 1986; 67: 1215-1223.
160. Gulba D C, Fischer K, Barthels M, et al. Low dose urokinase preactivated natural pro-urokinase for thrombolysis in acute myocardial infarction. Am J Cardiol 1989; 63: 1025-1031.
161. Gurewich V, Pannell R. A comperative study of the efficacy and specificity of tisue plasminogen activator and prourokinase: demonstration of synergism and of different thresholds of non-selectivity. Thromb Res 1986; 44: 217-228.
162. Gurewich V, Pannell R, Louie S, Kelley P. Fibrin-specific lysis of pulmonary emboli by prourokinase (pro-UK) in rabbits and dogs. In: Davidson J F, Donati M B, Cocchieri S (eds). Progress in Fibrinolysis VII. Edinburgh, Churchill Livingstone, 1985: 59-62.
163. van de Werf F, Vanhaecke J, de Geest H, Verstraete M, Collen D. Coronary thrombolysis with recombinant single-chain urokinase-type plasminogen activator in patients with acute myocardial infarction. Circulation 1986; 74: 1066-1070.
164. Bode C, Schuler G, Nordt T, et al. Intravenous thrombolytic therapy with a combination of single-chain urokinase-type plasminogen activator in acute myocardial infarction. Circulation 1990; 81: 907-913.
165. PRIMI Trial Study Group. Randomised double-blind trial of recombinant pro-urokinase against streptokinase in acute myocardial infarction. Lancet 1989; I: 863-868.
166. Diefenbach C, Erbel R, Pop T, et al. Recombinant single-chain urokinase-type plasminogen activator during acute myocardial infarction. Am J Cardiol 1988; 61: 966-970.
167. Gulba D C, Bode C, Sen S, et al. Multicenter dose-finding trial for thrombolysis with urokinase preactivated Pro-urokinase (TCL 598) in acute myocardial infarction. Cath Cardiovasc Diagn 1992; 26: 177-184.
168. Zarich S W, Kowalchuk G J, Weaver W D, et al. Sequential combination thrombolytic therapy for acute myocardial infarction: results of the Pro-urokinase and t-PA enhancement of thrombolysis (PATENT) trial. J Am Coll Cardiol 1995; 26: 374-379.
169. Loscalzo J, Wharton T, Kirshenbaum J M, et al. Clot-selective coronary thrombolysis with pro-urokinase. Circulation 1989; 79: 776-782.
170. Gulba D C, Fischer K, Barthels M, et al. Potentiative effect of heparin in thrombolytic therapy of evolving myocardial infarction with natural pro-urokinase. Fibrinolysis 1989; 3: 165-173.
171. Gulba D C, Bode C, Sen S, Topp J, Fischer K, Daniel W G. Coronary thrombolysis with urokinase preactivated intravenous pro-urokinase. JACC 1989; 13: 193A(Abstract).
172. Tebbe U, Windeler J, Boesel I, et al. Thrombolysis with recombinant unglycosylated single-chain urokinase-type plasminogen activator (Saruplase) in acute myocardial infarction: influence of heparin on early patency rate (LIMITS Study). J Am Coll Cardiol 1995; 26: 365-373.
173. Michels R, Hoffmann H, Windeler J, Barth H, Hopkins G, on behalf of the SUTAMI Investigators: A double-blind multicenter comparison of the efficacy and safety of Saruplase and Urokinase in the treatment of acute myocardial infarction: report of the SUTAMI Study Group. J Thrombos Thrombolys 1995; 2: 117-124.
174. Bär F W, Meyer J, Vermeer F, et al. Comparison of Saruplase and Alteplase in acute myocardial infarction. Am J Cardiol 1997; 79: 727-732.
175. Tebbe U, Michels R, Adgey J, et al. Randomized, double-blind study comparing Saruplase with Streptokinase therapy in acute myocardial infarction: the COMPASS equivalence trial. J Am Coll Cardiol 1998; 31: 487-493.
176. Gulba D C L, Gaffney P, Creighton L, Gallimore M J, Rees W, Lichtlen P R. The fate of single chain urokinase (SCUPA) during its use for the treatment of myocardiol infrarction (AMI). Thromb Haemost 1989; 62: 230(Abstract).
177. Gulba D C. Biochemische, pharmakologische und klinische Eigenschaften neuer Thrombolytika. Internist 1996; 37: 552-566.
178. Grines C L, Browne K F, Rothbaum D, et al. A comparison of immediate angioplasty with thrombolytic therapy for acute myocardial infarction. N Engl J Med 1993; 328: 673-679.
179. Zijlstra F, de Boer M J, Hoorntje J C A, Reiffers S, Reiber J H C, Suryapranata H. A comparison of immediate coronary angioplasty with intravenous streptokinase in acute myocardial infarction. N Engl J Med 1993; 328: 680-684.
180. Gibbons R J, Holmes D R, Reeder G S, Bailey K R, Hopfenspirger M R, Gersh B J, for the Mayo Coronary Care Unit and Catheterization Laboratory Groups: Immediate angioplasty compared with the administration of a thrombolytic agent followed by conservative treatment for myocardial infarction. N Engl J Med 1993; 328: 685-691.
181. Ribeiro E E, Silva L A, Carneiro R, et al. Randomized trial of direct coronary angioplasty versus intravenous streptokinase in acute myocardial infarction. J Am Coll Cardiol 1993; 22: 376-380.
182. Martin U, Bader R, Böhm E, Kohnert U, von Möllendorf E, Fischer S, Sponer G. BM O6.022: a novel recombinant plasminogen activator. Cardiovasc Drug Rev 1993; 11: 299-311.
183. Martin U, von Möllendorf E, Akpan W, Kientsch-Engel R, Kaufmann B, Neugebauer G. Pharmacokinetic and hemostatic properties of the recombinant plasminogen activator BM 06.022 in healthy volunteers. Thromb Haemostas 1991; 66: 569-574.
184. Seifried E, Müller M M, Martin U, König R, Hombach V. Bolus application of a novel recombinant plasminogen activator in acute myocardial infarction patients: pharmacokinetics and effects on the hemostatic system. Ann N Y AcadSci 1991; 667: 417-420.
185. Martin U, Sponer G, Strein K. Differential fibrinolytic properties of the recombinant plasminogen activator BM 06.022 in human plasma and blood clot systems in vitro. Blood Coag Fibrino 1992; 4: 235-242.
186. Kohnert U, Rudolph R, Verheijen J H, et al. Biochemical properties of the kringle 2 and protease domains maintained in the refolded t-PA deletion variant DM 06.022. Protein Engineering 1992; 5: 93-100.
187. Martin U, Sponer G, Strein K. Influence of hepatic and renal failure on pharmacokinetic properties of the novel recombinant plasminogen activator BM 06.022 in rats. Drug Metab Disposition 1993; 21: 236-241.
188. Martin U, Köhler J, Sponer G, Strein K. Pharmacokinetics of the novel recombinant plasminogen activator BM 06.022 in rats, dogs, and non-human primates. Fibrinolysis 1992; 6: 39-43.
189. Martin U, Fischer S, Sponer G. Influence of heparin and systemic lysis on coronary blood flow after reperfusion induced by the novel recombinant plasminogen activator BM 06.022 in a canine model of coronary thrombosis. J Am Coll Cardiol 1993; 22: 914-920.
190. Martin U, Sponer G, Strein K. Hirudin and solutroban improve coronary blood flow after reperfusion induced by the novel recombinant plasminogen activator BM 06.022 in a canine model of coronary artery thrombosis. Int J Hematol 1992; 56: 143-153.
191. Barbash G I, Reiner J, White H D, et al. Evaluation of paradoxic beneficial effects of smoking in patients receiving thrombolytic therapy for acute myocardial infarction: mechanism of the "smoker's paradox" from the GUSTO-I trial, with angiographic insights. JACC 1995; 26, No. 5: 1222-1229.
192. von Essen R, Neuhaus K-L, Markreiter M, et al. Double bolus of r-PA in the dosefinding. Results of the GRECO II study. JACC 1992; 19: 274A(Abstract).
193. Tebbe U, von Essen R, Smolarz A, et al. Open, noncontrolled dose-finding study with a novel recombinant plasminogen activator (BM 06.022) given as a double bolus in patients with acute myocardial infarction. Am J Cardiol 1993; 72: 518-524.
194. Smalling R W, Bode C, Kalbfleisch J, et al. More rapid, complete, and stable coronary thrombolysis with bolus administration of reteplase compared with alteplase infusion in acute myocardial infarction. Circulation 1995; 91: 2725-2732.
195. Bode C, Smalling R W, Berg G, et al. Randomized comparison of coronary thrombolysis achieved with double-bolus reteplase (recombinant plasminogen activator) and front-loaded, accelerated alteplase (recombinant tissue plasminogen activator) in patients with acute myocardial infarction. Circulation 1996; 94: 891-898.
196. International Joint Efficacy Comparison of Thrombolytics: Randomised, double-blind comparison of reteplase double-bolus administration with streptokinase in acute myocardial infarction (INJECT): trial to investigate equivalence. Lancet 1995; 346: 329-336.
197. The Global Use of Strategies to Open Occluded Coronary Arteries (GUSTO III) Investigators: A comparison of reteplase with alteplase for acute myocardial infarction. N Engl J Med 1997; 337: 1118-1123.
198. Hotchkiss A, Refino C J, Leonard C K, et al. The influence of carbohydrate structure on the clearance of recombinant tissue-type plasminogen activator. Thromb Haemost 1988; 60: 255-261.
199. Bennett W F, Paoni N F, Keyt B A, et al. High resolution analysis of functional determinants on human tissue-type plasminogen activator. J Biol Chem 1991; 266: 5191-5201.
200. Madison E L, Goldsmith E J, Gerard R D, Gething M J H, Sambrook J F, Basel-Duby R S. Amino acid residues that affect interaction of tissue type plasminogen activator with plasminogen activator inhibitor 1. Proc Natl AcadSci USA 1990; 87: 3530-3533.
201. Madison E L, Goldsmith E J, Gerard R D, Gething M J H, Sembrook J F. Serpin-resistant mutants of human tissue-type plasminogen activator. Nature 1989; 339: 721-724.
202. Vlasuk G P, Ramjit D, Fujita T, et al. Comparison of the in vivo anticoagulant properties of standard Heparin and the highly selctive factor Xa inhibitors Antistasin and tick anticoagulant peptide (TAP) in a rabbit model of venous thrombosis. Thromb Haemost 1991; 65: 257-262.
203. Garabedian H D, Svizzero T A, Guerrero J L, Pena L C, Love T W, Leinbach R C, Gold H K A. new dosing strategy for TNK variant of tissue plasminogen activator eliminates heparin and reduces bleeding without loss of thrombolytic efficacy. Circulation 1995; 92 suppl.: I-740(Abstract).
204. Cannon C P, Love T W, McCabe C H, et al. TNK-tissue plasminogen activator in myocardial infarction (TIMI) 10: results of the initial patients in the TIMI 10 pilot - a phase 1, pharmacokinetics trial. Circulation 1995; 92 suppl.: 1-415(Abstract).
205. Cannon C P, McCabe C H, Gibson M, et al. TNK-tissue plasminogen activator in acute myocardial infarction. Results of the Thrombolysis in Myocardial Infarction (TIMI) 10 A dose-ranging trial. Circulation 1997; 95: 351-356.
206. Lijnen H R, Collen D. Strategies for the improvement of thrombolytic agents. Thromb Haemost 1991; 66(1): 88-110.
207. Lijnen H R, van Hoef B, Vandenbossche L, Collen D. Biochemical properties of natural and recombinant staphylokinase. Fibrinolysis 1992; 6: 214-225.
208. Krätzschmar J, Haendler B, Langner G, et al. The plasminogen activator family from salivary gland of the vampire bat Desmodus rotundus: cloning and expression. Gene 1991; 105: 229-237
209. Lack C H. Staphylokinase: an activator of plasma protease. Nature 1948; 161: 559-560.
210. Collen D, Silence K, Demarsin E, De Mol M, Lijnen H R. Isolation and characterisation of natural and recombinant staphylokinase. Fibrinolysis 1992; 6: 203-213.
211. Lijnen H R, van Hoef B, de Cock F, Okada K, Ueshima S, Matsuo O, Collen D. On the mechanism of fibrin-specific plasminogen activation by staphylokinase. J Biol Chem 1991; 266: 11826-11832.
212. Collen D, van de Werf F. Coronary thrombolysis with recombinant staphylokinase in patients with evolving myocardial infarction. Circulation 1993; 87: 1850-1853.
213. Collen D, de Cook F, Vanlinthout I, Declerck P J, Lijnen H R, Stassen J M. Comparative thrombolytic and immunogenic properties of staphylokinase and streptokinase. Fibrinolysis 1992; 6: 232-242.
214. Collen D, de Cock F, Stassen J M. Comperative immunogenicity and thrombolytic properties toward arterial and venous thrombi of streptokinase and recombinant staphylokinase in baboon. Circulation 1993; 87: 996-1006.
215. Collen D, Lijnen H. Staphylokinase, a fibrin specific plasminogen activator with therapeutic potential. Blood 1994; 84: 680-686.
216. Vanderschueren S, Lijnen H R, Collen D. Properties of staphylokinase and its potential as a thrombolytic agent. Fibrinolysis 1995; 9 suppl. 1: 87-90(Abstract).
217. Vanderschueren S, Barrios L, Kerdsinachai P, et al. A randomized trail of recombinant staphylokinase versus alteplase for coronary artery patency in acute myocardial infarction. Circulation 1995; 92: 2044-2049.
218. Okada K, Lijnen H R, Moreau H, Vanderschueren S, Collen D. Procoagulant properties of intravenous staphylokinase versus tissue-type plasminogen activator. Thromb Haemost 1996; 76: 857-859.
219. Collen D, de Cock F, Demarsin E, et al. Recombinant staphylokinase variants with altered immunoreactivity. III: Species variability of antibody binding patterns. Circulation 1997; 95: 455-462.
220. Collen D, Stockx L, Lacroix H, Suy R, Vanderschueren S. Recombinant staphylokinase variants with altered immunoreactivity. IV: Identification of variants with reduced antibody induction but intact potency. Circulation 1997; 95: 463-472.
221. Gulba D C, Praus M, Witt W. DSPA alpha - properties of the plasminogen activator of the vampire bat desmodus rotundus. Fibrinolysis 1995; 9 suppl. I: 91-96.
222. Bergum P W, Gardell S J. Vampire bat salivary plasminogen activator exhibits a strict and fastidious requirement for polymeric fibrin as its cofactor, unlike human tissue-type plasminogen activator. JBC 1994; 267: 17726-17731.
223. Schleuning W-D, Alagon A, Boidol W, et al. Plasminogen Activation in Fibrinolysis, on Tissue Remodeling and in Development, Vol. 667. New York, The New York Academy of Science 1992; 395-403.
224. Hare T R, Gardell S J. Vampire bat salivary plasminogen activator promotes robust lysis of plasma clots in a plasma millieu without causing fluid phase plasminogen activation. Thromb Haemost 1992; 68: 165-169.
225. Praus M, Scheu P, Schleuning W-D, Witt W. Effects of pressure gradients on in vitro blood clot lysis induced by the bat plasminogen activator DSPA-Alpha 1 and t-PA. Ann Haematol 1993; 66 (Suppl. I): A43(Abstract).
226. Witt W, Baldus B, Bringmann P, Cashion L, Donner P, Schleuning W-D. Thrombolytic properties of desmodus rotundus (vampire bat) salivary plasminogen activator in experimental pulmonary embolism in rats. Blood 1992; 79, NO 5: 1213-1217.
227. Witt W, Maass B, Baldus B, Hildebrand M, Donner P, Schleuning W-D. Coronary thrombolysis with desmodus salibary plasminogen activator in dogs - fast and persistent recanalization by intravenous bolus administration. Circulation 1994; 90: 421-426.
228. Gardell S J, Ramjit D R, Stabilito I I, et al. Effective thrombolysis without marked plasminemia after bolus intravenous administration of a vampire bat salivary plasminogen activator in rabbits. Circulation 1991; 84: 244-253.
229. Mellott M J, Stabilito I I, Holahan M A, Cuca G C, Wang S, Li P, Gardell S J. Vampire bat salivary plasminogen activator promotes rapid and sustained reperfusion without concomitant. Arterioscl Thromb 1992; 12: 212-221.
230. Muschick P, Zeggert D, Donner P, Witt W. Thrombolytic Properties of Desmodus (Vampire Bat) Saivary Plasminogen Activator DSPA-Alpha-1, Alteplase and Streptokinase Following Intravenous Bolus Injectioon in a Rabbit Model of Carotid Artery Thrombosis. Fibrinolysis 1993; 7: 284-290.
231. Burton G, Graichen G, Witt W. Effect of the novel thrombolytic DSPA alpha 1 on venipuncture bleeding time in the rat: Comparison to Anistreplase and t-PA. Thromb Haemost 1993; 69(6): 842.
232. Gulba D C, Praus M, Dechend R, et al. Update on the toxicology and pharmacology of rDSPA alpha 1 (Bat-PA) in animals and humans. Fibrinolysis & Proteolysis 1997; 11 suppl. 2: 55-62.
233. Witt W, Kirchhoff D, Woy P, Zierz R, Bhargava A S. Antibody formation and effects onendogenous fibrinolysis after repeated administration of DSPA alpha 1 in rats. Fibrinolysis 1994; 8 Suppl. 1: 66.
234. Gulba D C, Barthels M, Westhoff-Bleck M, et al. Increased thrombin levels during thrombolytic therapy in acute myocardial infarction. Relevance for the success of therapy. Circulation 1991; 83: 937-944.
235. Gulba D, Barthels M, Reil G-H, Lichtlen P. Thrombin-antithrombin-III-complex level as early predictor of reocclusion after successful thrombolysis. Lancet 1988; 2: 97
236. Eisenberg P R, Sherman L A, Jaffe A S. Paradoxic elevation of fibrinopeptide A after streptokinase: evidence for continued thrombosis despite intensive fibrinolysis. JACC 1987; 10: 527-529.
237. Ewald G A, Eisenberg P R. Increased procoagulant activity in response to fibrinolytic agents due to plasmin-mediated activation of the contact system. Thromb Haemost 1993; 69: 823(Abstract).
238. Rapold H J, Kuemmerli H, Weiss M, Baur H, Haeberli A. Monitoring of fibrin generation during thrombolytic therapy of acute myocardial infarction with recombinant tissue-type plasminogen activator. Circulation 1989; 79: 980-989.
239. Herrick J B. Clinical features of sudden obstruction of the coronary arteries. J Am Med Ass 1912; 59: 2015-2020.
240. Markwardt F. Hirudin and derivatives as anticoagulant agents. Thromb Haemost 1991; 66: 141-152.
241. Markwardt F. Hirudin: the promising antithrombotic. Cardiovasc Drug Rev 1992; 10: 211-232.
242. Mellott M J, Stranieri M T, Sitko G R, Stabilito I I, Lynch J J, Vlasuk G P. Enhancement of recombinant tissue plasminogen activator-induced reperfusion by recombinant tick anticoagulant peptide, a selective factor Xa inhibitor, in a canine model of femoral arterial thrombosis. Fibrinolysis 1993; 7: 195-202.
243. King S B, Lembo N J, Weintraub W S, et al. A randomized trial comparing coronary angioplasty with coronary bypass surgery. N Engl J Med 1994; 331: 1044-1050.
244. Bode C, Gulba D, Huber K, Runge M S. New approaches in plasminogen activator therapy. Am Hematol 1996; 73 (suppl 1): S1-S8.
245. Bode C, Noroff T K, Kohler B, Weaver W D, Smalling R W. Novel tissue plasminogen activators: reteplase. Ini Becker R C (ed.). Textbook of Coronary Thrombosis and Thrombolysis. Boston: Kluwer Academic, 1997: 263-268.