Hirudins: From leeches to man

Seminars in Thrombosis and Hemostasis

Volumn 22, Issue 2, 1996, Pages 185-196

  Wallis, Robert B ^a  

^a Biopharm UK Ltd   (United Kingdom)

Author keywords

Acute coronary syndrome; Hirudin; Myocardial infarction; Thrombin; Venous thrombosis

Indexed keywords

HIRUDIN; THROMBIN;

ANTICOAGULATION; CONFERENCE PAPER; DRUG ISOLATION; DRUG POTENCY; DRUG PROTEIN BINDING; FIBRIN CLOT; HUMAN; LEECH; PRIORITY JOURNAL; THROMBOSIS;

EID: 0030015015     PISSN: 00946176     EISSN: None     Source Type: Journal    
DOI: 10.1055/s-2007-999007     Document Type: Conference Paper

References (95)

1. Haycraft JB: Über die Einwirkung eines Sekretes des offiziellen Blutegels auf die Gerinnbarkeit des Blutes. Arch Exp Pathol Pharmakol 18:209-217, 1884.
2. Bodong A: Über Hirudin. Arch Exp Pathol Pharmakol 52:242-261, 1905.
3. Tripier D: Hirudin: A family of iso-proteins. Isolation and sequence determination of new hirudins. Folia Haematol 115:30-35, 1988.
4. Scharf M, J Engels, D Tripier: Primary structures of new 'iso-hirudins'. FEBS Lett 255:105-110, 1989.
5. Johnson P, P Sze, R Winant, PW Payne, JB Lazar: Biochemistry and genetic engineering of hirudin. Semin Thromb Hemostas 15: 302-315, 1989.
6. Peterson TE, HR Roberts, L Sottrup-Jensen, S Magnussen: Primary structure of hirudin, a specific thrombin inhibitor. In: Peters H (Ed): Protides of the Biological Fluids. Pergamon Press, Oxford, UK, 1976, pp 145-149.
7. Dodt J, H-P Mueller, U Seemueller, J-Y Chang: The complete amino acid sequence of hirudin, a thrombin specific inhibitor. Application of colour carboxymethylation. FEBS Lett 165:180-184, 1984.
8. Harvey RP, E Degryse, L Stefani, F Schamber, J-P Cazenave, M Courtney, P Tolstoyev, J-P Lecocq: Cloning and expression of cDNA coding for the anticoagulant hirudin from the bloodsucking leech, Hirudo medicinalis. Proc Nat Acad Sci USA 83: 1084-1088, 1986.
9. Dodt J, W Machleidt, U Seemüller, R Maschler, H Fritz: Isolation and characterization of hirudin isoinhibitors and sequence analysis of hirudin PA. Biol Chem Hoppe Seyler 367:803-811, 1986.
10. Maerki WE, H Grossenbacher, MG Gruetter, MH Liersch, B Meyhack, J Heim: Recombinant hirudin: Genetic engineering and structure analysis. Semin Thromb Haemostas 17:88-93, 1991.
11. Komatsu Y, S Misawa, A Sukusada, Y Ohba, H Hayashi: CX-397, a novel recombinant hirudin analog having a hybrid sequence of hirudin variants -1 and -2. Biochem Biophys Res Commun 196: 773-779, 1993.
12. Haruyama H, K Wuthrich: Conformation of recombinant desulfatohirudin in aqueous solution determined by nuclear magnetic resonance. Biochemistry 28:4301-4312, 1989.
13. Gruetter MG, JP Priestle, J Rahuel, H Grossenbacher, W Bode, J Hofsteenge, SR Stone: Crystal structure of the thrombin-hirudin complex: A novel mode of serine protease inhibition. EMBO J 9:2361-2365, 1990.
14. Rydel TJ, KG Ravichandran, A Tulinsky, W Bode, R Huber, C Roitsch. JW Fenton: The structure of a complex of recombinant hirudin and human alpha-thrombin. Science 249:277-280, 1990.
15. Stone SR, J Hofsteenge: Kinetics of the inhibition of thrombin by hirudin. Biochemistry 25:4622-4628, 1986.
16. Braun PJ, S Dennis, J Hofsteenge, SR Stone: Use of site-directed mutagenesis to investigate the basis for the specificity of hirudin. Biochemistry 27:6517-6522, 1988.
17. Dennis S, A Wallace, J Hofsteenge, SR Stone: Use of fragments of hirudin to investigate thrombin-hirudin interaction. Eur J Biochem 188:61-66, 1990.
18. Jackman MP, MAA Parry, J Hofsteenge, SR Stone: Intrinsic fluorescence changes and rapid kinetics of the reaction of thrombin with hirudin. J Biol Chem 267:15375-15383, 1992.
19. Talbot M: Biology of recombinant hirudin (CGP 39393): A new prospect in the treatment of thrombosis. Semin Thromb Hemostas 15:293-301, 1989.
20. Pizzo SV, RC Friedberg, P Sze, R Winant, D Hudson, JM Lazaar, PH Johnson: Recombinant hirudin displaces human factor Xa from its endothelial binding sites. Thromb Res 57:803-806, 1990.
21. Marbet GA, M Verstraete, J Kienast, P Graf, B Hoet, DA Tsakaris, G Silling-Engelhardt, P Close: Clinical pharmacology of intravenously administered recombinant desulfatohirudin (CGP 39393) in healthy volunteers. J Cardiovasc Pharmacol 22:364-372, 1993.
22. Bichler J, B Fichtl, M Siebeck, H Fritz: Pharmacokinetics and pharmacodynamics of hirudin in man after single subcutaneous and intravenous bolus administration. Drug Res 38:704-711, 1988.
23. Lindhout T, R Blezer, HC Hemker: The anticoagulant mechanism of action of recombinant hirudin (CGP 39393) in plasma. Thromb Haemostas 64:464-468, 1990.
24. Garcia JGN, JL Aschner, AB Malik: Regulation of thrombin-induced endothelial cell barrier dysfunction and prostaglandin synthesis. In: Berliner LJ (ed): Thrombin Structure and Function. Plenum Press, New York, 1992, pp 397-430.
25. Suidan HS, SR Stone, BA Hemmings, D Monard: Thrombin causes neurite retraction in neuronal cells through activation of cell surface receptors. Neuron 8:363-375, 1972.
26. Bar-Shavit R, M Benezra, V Sabbah, E Dejana, I Vlodavsky, GD Wilner: Functional domains in thrombin outside the catalytic site: Cellular interactions. In: Berliner LJ (Ed): Thrombin Structure and Function. Plenum Press, New York, 1992, pp 315-350.
27. Greco NJ: Effect of chemical modification of α-thrombin on its reaction with platelets and nucleated cells. In: Berliner LJ (Ed): Thrombin Structure and Function. Plenum Press, New York, 1992, pp 275-314.
28. Koike K, H Holmsen: Requirement for thrombin receptor occupancy during secretion under aggregating and non-aggregating conditions. Thromb Haemostas 58:1053-1059, 1987.
29. Lages B, H Weiss: Dependance of human platelet functional responses on divalent cations: Aggregation and secretion in heparin and hirudin anticoagulated platelet-rich plasma and the effects of chelating agents. Thromb Haemostas 45:173-179, 1981.
30. Glusa E, F Markwardt: Platelet functions in recombinant hirudin-anticoagulated blood. Haemostasis 20:112-118, 1990.
31. Mustard F: Factors responsible for ADP-induced release reaction of human platelets. Am J Physiol 228:1757-1765, 1975.
32. Badimon L, JJ Badimon, R Lassila, M Heras, JH Chesebro, V Fuster: Thrombin regulation of platelet interaction with damaged vessel wall and isolated collagen type 1 at arterial flow conditions in a porcine model: Effects of hirudins, heparin, and calcium chelation. Blood 78:423-434, 1991.
33. Markwardt F, G Fink, B Kaiser, H-P Kloecking, G Nowak, M Richter, J Stuerzebecher: Pharmacological survey of recombinant hirudin. Pharmazie 43:202-207, 1988.
34. Markwardt F, B Kaiser, G Nowak: Studies on antithrombotic effects of recombinant hirudin. Thromb Res 54:377-388, 1989.
35. Gerna M, A Molinari, F La Tour, G Nitti, J Lansen: Pharmacokinetics and pharmacodynamics of recombinant hirudin in cynomolgus monkeys. Thromb Res 65(Suppl 1):S157, 1992.
36. Grötsch H, M Hropot, G Berscheid, P Crause, V Malerczyk, G Adipoulos, G Haun, B Husak: Pharmacokinetic investigations of the α-human thrombin-hirudin complex in rhesus monkeys. Thromb Res 66:271-275, 1992.
37. Meyer BH, HG Luus, FO Müller, PN Badenhorst, H-J Roethig: The pharmacology of recombinant hirudin, a new anticoagulant. South Afr J Med 78:268-270, 1990.
38. Nowak G: Pharmacokinetics of hirudin. Semin Thromb Hemostas 17:145-149, 1991.
39. Nowak G, E Bucha, T Gööck, H Thieler, F Markwardt: Pharmacology of r-hirudin in renal impairment. Thromb Res 66:707-715, 1992.
40. Maack T, CH Park, MJF Camargo: Renal filtration, transport and metabolism of proteins. In: Seldin DW, G Giebisch (Eds): The Kidney: Physiology and Pathophysiology. 2nd ed. Raven Press, New York, 1992, pp 3005-3028.
41. Bichler J, B Fichtl, M Siebeck, H Fritz: Pharmacokinetics and pharmacodynamics of hirudin in man after single subcutaneous and intravenous bolus administration. Drug Res 38:704-711, 1988.
42. Markwardt F, G Nowak, J Stuerzebecher, G Vogel: Clinicopharmacological studies with recombinant hirudin. Thromb Res 52:393-400, 1988.
43. Marbet GA, M Verstraete, J Kienast, P Graf, B Hoet, DA Tsakaris, G Silling-Engelhardt, P Close: Clinical pharmacology of intravenously administered recombinant desulfatohirudin (CGP 39393) in healthy volunteers. J Cardiovasc Pharmacol 22:364-372, 1993.
44. Bara L, MF Bloch, MM Samama: A comparative study of recombinant hirudin and standard heparin in the Wessler model. Thromb Res 68:167-174, 1992.
45. Talbot MD, J Ambler, KD Butler, VS Findlay, KA Mitchell, RF Peters, MF Tweed, RB Wallis: Recombinant desulphatohirudin (CGP 39393) anticoagulant and antithrombotic properties in vivo. Thromb Haemostas 61:77-80, 1989.
46. Freund M, JP Cazenave, M Courtney, E Degryse, C Roitsch, A Bernat, D Delebassee, G Defreyn, J-P Maffrand: Inhibition by recombinant hirudins of experimental venous thrombosis and disseminated intravascular coagulation induced by tissue factor in rats. Thromb Haemostas 63:187-192, 1992.
47. Wessler S, SM Reimer, MC Sheps: Biologic assay of a thrombosis-inducing activity in human serum. J Appl Physiol 14:943-946, 1959.
48. Hladovec J: A sensitive model of venous thrombosis in rats. Thromb Res 43:539-544, 1986.
49. Monreal M: Comparative study on the antithrombotic efficacy of hirudin, heparin and a low molecular weight heparin in preventing experimentally induced venous thrombosis. Haemostasis 23:179-183, 1993.
50. Eriksson BI, P Kälebo, S Ekman, S Lindbratt, R Kerry, P Close: Direct thrombin inhibition with rec-hirudin CGP 39393 as prophylaxis of thromboembolic complications after total hip replacement. Thromb Haemostas 72:227-231, 1994.
51. Parent F, F Bridey, M Dreyfus, D Musset, G Grimon, P Duroux, D Meyer, G Simmonneau: Treatment of severe venous thromboembolism with intravenous hirudin (HBW 023): An open pilot study. Thromb Haemostas 70:386-388, 1993.
52. Agnelli G, C Pascucci, B Cosmi, GG Nenci: The comparative effects of recombinant hirudin (CGP 39393) and standard heparin on thrombus growth in rabbits. Thromb Haemostas 63:204-207, 1990.
53. Biemond BJ, M Levi, MT Nurmohamed, HR Büller, J ten Cate: Additive effect of the combined administration of low molecular weight heparin and recombinant hirudin on thrombus growth in a rabbit jugular vein thrombosis model. Thromb Haemostas 72: 377-380, 1994.
54. Agnelli G: Sustained antithrombotic activity of hirudin after its plasma clearance: Comparison with heparin. Blood 80:960-965, 1992.
55. Naski MC, JA Shafer: Alpha-thrombin within fibrin clots: Inactivation of thrombin by antithrombin-III. Thromb Res 69:453-465, 1993.
56. Liu CY, HL Nossel, KL Kaplan: The binding of thrombin by fibrin. J Biol Chem 254:10421-10425, 1979.
57. Kaminski M, J McDonagh: Studies on the mechanism of thrombin: Interaction with fibrin. J Biol Chem 258:10530-10535, 1983.
58. Wilner GD, MP Danitz, MS Mudd, KH Hsieh, JW Fenton: Selective immobilisation of α-thrombin by surface-bound fibrin. J Lab Clin Med 97:403-411, 1981.
59. Kaczmarck E, J McDonagh: Thrombin binding to the Aα-, Bβ-and γ-chains of fibrinogen and to their remnants containing fragment E. J Biol Chem 263:13896-13900, 1988.
60. Berliner LJ, Y Sugawara, JW Fenton II: Human α-thrombin binding to non polymerised fibrin-sepharose: Evidence for an anionic binding region. Biochemistry 24:7005-7009, 1985.
61. Rubens FD, JI Weitz, JL Brash, RL Kinlough-Rathbone: The effect of antithrombin III-independent thrombin inhibitors and heparin on fibrin accretion onto fibrin-coated polyethylene. Thromb Haemostas 69:130-134, 1993.
62. Weitz JI, M Hudoba, D Massel, J Maraganore, J Hirsh: Clot-bound thrombin is protected from inhibition by heparin-antithrombin III but is susceptible to inactivation by antithrombin III-independent inhibitors. J Clin Invest 86:385-391, 1990.
63. Mirshahi M, J Soria, C Soria, R Faivre, H Lu, M Courtney, C Roitsch, D Tripier, JP Caen: Evaluation of the inhibition by heparin and hirudin of coagulation activation during r-tPA-induced thrombolysis. Blood 74:1025-1030, 1989.
64. Electricwala A, T Atkinson: Effect of hirudin on tissue plasminogen activator induced clot lysis. Blood Coag Fibrinolysis 1: 267-272, 1990.
65. Kerins DM, L Roy, GA FitzGerald, DJ Fitzgerald: Platelet and vascular function during coronary thrombolysis with tissue type plasminogen activator. Circulation 80:1718-1725, 1989.
66. Fitzgerald DJ, F Catella, L Roy, GA FitzGerald: Marked platelet activation in vivo after intravenous streptokinase in patients with acute myocardial infarction. Circulation 77:132-150, 1988.
67. Gulba DC, M Barthels, G-H Reil, PR Lichtlen: Thrombin/anti-thrombin-III complex level as early predictor of reocclusion after successful thrombolysis. Lancet ii:97, 1988.
68. Gulba DC, M Barthels, M Westhoff-Bleck, S Jost, W Rafflenbeul, WG Daniel, H Hecker, PR Lichtlen: Increased thrombin levels during thrombolytic therapy in acute myocardial infarction. Relevance for the success of therapy. Circulation 83:937-944, 1991.
69. Gulba DC, WG Daniel, R Simon, S Jost, M Barthels, I Amende, W Rafflenbeul, PR Lichtlen: Role of thrombolysis and thrombin in patients with acute coronary occlusion during percutaneous transluminal coronary angioplasty. J Am Coll Cardiol 16:563-568, 1990.
70. Eisenberg PR, BE Sobel, AS Jaffe: Activation of prothrombin accompanying thrombolysis with recombinant tissue-type plasminogen activator. J Am Coll Cardiol 19:1065-1069, 1992.
71. Haskel EJ, NA Prager, BE Sobel, DR Abendschein: Relative efficacy of antithrombin compared with antiplatelet agents in accelerating coronary thrombolysis and preventing early reocclusion. Circulation 83:1048-1056, 1991.
72. Rigel DF, RW Olson, RW Lappe: Comparison of hirudin and heparin as adjuncts to streptokinase thrombolysis in a canine model of coronary thrombosis. Circ Res 72:1091-1102, 1993.
73. Mruk JS, JH Chesebro, MWI Webster, M Heras, DE Grill, V Fuster: Hirudin markedly enhances thrombolysis with rt-PA. Circulation 82(Suppl III):135, 1990.
74. Cannon CP, CH McAbe, TD Henry, MJ Schweiger, RS Gibson, HS Mueller, RC Becker, NS Kleiman, M Haugland, JL Anderson, BL Sharaf, SJ Edwards, WJ Rogers, DO Williams, E Braunwald: A pilot trial of recombinant desulfatohirudin compared with heparin in conjunction with tissue-type plasminogen activator and aspirin for acute myocardial infarction: Results of the thrombolysis in myocardial infarction (TIMI) 5 trial. J Am Coll Cardiol 223:993-1003, 1994.
75. Homeister JW, JK Mickelson, PT Hoff, BR Lucchesi: Recombinant hirudin reduces the incidence of thrombotic occlusion in a canine model of coronary artery injury. Coronary Artery Dis 2:237-246, 1991.
76. 2 and thrombin. Thromb Haemostas 71:366-374, 1994.
77. Butler KD, J Ambler, S Dolan, J Giddings, MD Talbot, RB Wallis: A non-occlusive model of arterial thrombus formation in the rat and its modification by inhibitors of platelet function, or thrombin activity. Blood Coag Fibrinolysis 3:155-165, 1992.
78. Heras M, JH Chesebro, MWI Webster, JF Mruk, DB Grill, WJ Penny, EJW Bowie, L Badimon, V Fuster: Hirudin, heparin, and placebo during deep arterial injury in the pig. The in vivo role of thrombin in platelet-mediated thrombosis. Circulation 82:1476-1484, 1990.
79. Heras M, JH Chesebro, WJ Penny, KR Bailey, L Badimon, V Fuster: Effects of thrombin inhibition on the development of acute platelet-thrombus deposition during angioplasty in pigs. Heparin versus recombinant hirudin, a specific thrombin inhibitor. Circulation 79:657-665, 1989.
80. van den Bos AA, JW Deckers, GR Heyndrickx, G-J Laarman, H Suryapranata, F Zijlstra, P Close, JJMM Rijnierse, HR Büller, PW Serruys: Safety and efficacy of recombinant hirudin (CGP 39393) versus heparin in patients with unstable angina undergoing coronary angioplasty. Circulation 88:2058-2066, 1993.
81. Buchwald AB, D Sandrock, C Unterberg, M Ebbecke, K Nebendahl, S Luders, DL Munz, V Wiegand: Platelet and fibrin deposition on coronary stems in minipigs: Effect of hirudin versus heparin. J Am Coll Cardiol 21:249-254, 1993.
82. Falk E: Plaque rupture with severe pre-existing stenosis precipitating coronary thrombosis: Characteristics of coronary atherosclerotic plaques underlying fatal occlusive thrombi. Br Heart J 50: 127-134, 1983.
83. Davies MJ, AC Thomas: Plaque fissuring - the cause of acute myocardial infarction, sudden ischaemic death and crescendo angina. Br Heart J 53:363, 1985.
84. Fuster V, B Stein, JA Ambrose, L Badimon, JJ Badimon, JH Chesebro: Atherosclerotic plaque rupture and thrombosis: Evolving concepts. Circulation 82(Suppl II):47-59, 1990.
85. Topol EJ, V Fuster, RA Harrington, RM Califf, NS Klieman, DJ Kereiakes, M Cohen, A Chapekis, HK Gold, MA Tannenbaum, AK Rao, D Debowey, D Schwartz, M Henis, JH Chesebro: Recombinant hirudin for unstable angina pectoris. A multicentre, randomised angiographic trial. Circulation 89:1557-1566, 1994.
86. Walenga JM, MJ Koza, SJ Park, MR Terrell, R Piffare: Evaluation of CGP 39393 as the anticoagulant in cardiopulmonary bypass operation in a dog model. Ann Thorac Surg 58:1685-1689, 1994.
87. Dascombe WH, C Hong, KO Garrett, JG White, VA Lyle, JL Miller, PC Johnson: Artificial microvascular graft thrombosis: The consequences of platelet membrane glycoprotein 1b inhibition and thrombin inhibition. Blood 82:126-134, 1993.
88. GUSTO IIa Investigators: Randomised trial of intravenous heparin versus recombinant hirudin for acute coronary syndromes. Circulation 90:1631-1637, 1994.
89. Neuhaus K-L, R von Essen, U Tebbe, A Jessel, H Heinrichs, W Maurer, W Doring, D Harmjanz, V Kotter, E Kalhammer, H Simon, T Horacek: Safety observations from the pilot phase of a randomised trial: r-Hirudin for the improvement of thrombolysis (HIT III) study. Circulation 90:1638-1642, 1994.
90. Meyer BH, HG Luus, FO Muller, PN Badenhorst, MG Lotter, HJ Rothig, H Grotsch, B Rosenkranz: Recombinant hirudin, a new anticoagulant, has no effect on faecal blood loss. Br J Clin Pharmacol 33:524-526, 1992.
91. Verstraete M, M Nurmohamed, J Kienast, M Siebeck, G Silling-Engelhardt, H Büller, B Hoet, J Bichler, P Close: Biologic effects of recombinant hirudin (CGP 39393) in human volunteers. J Am Coll Cardiol 22:1080-1088, 1993.
92. Close P, J Bichler, R Kerry, S Ekman, HR Bueller, J Kienast, GA Marbet, W Schramm, MD Verstraete: Weak allergenicity of recombinant hirudin, CGP 39393 (™Revasc) in immunocompetent volunteers. Coronary Artery Dis 5:943-949, 1994.
93. Sarembock IJ, SD Gertz, LW Gimple, SD Owen, LW Powers, WC Roberts: Effectiveness of recombinant desulphatohirudin in reducing restenosis after balloon angioplasty of atherosclerotic femoral arteries in rabbits. Circulation 84:232-243, 1991.
94. Webster MWI, JH Chesebro, DE Grill, JJ Badimon, L Badimon, V Fuster: The thrombotic and proliferative response to angioplasty in pigs after deep arterial injury: Effect of intravenous thrombin inhibition with hirudin. Circulation 84(Suppl II):580, 1991.
95. Serruys PW, J-P Herrman, R Simon, W Rutsch, C Bode, G-J Laarman, R van Dijk, AA van den Bos, VAWM Umans, KAA Fox, P Close, JW Deckers for the HELVETICA Investigators: A comparison of hirudin with heparin in the prevention of restenosis after coronary angioplasty. N Engl J Med 333:757-763, 1995.