Download PDF
Thromb Haemost 1995; 74(01): 565-571
DOI: 10.1055/s-0038-1642739
Symposium
Plenary Lecture
Schattauer GmbH Stuttgart

Advances in Antithrombotic Therapy: Novel Agents

Alexander G G Turpie
McMaster University and Hamilton Civic Hospitals Research Centre, Hamilton, Ontario, Canada
,
Jeffrey I Weitz
McMaster University and Hamilton Civic Hospitals Research Centre, Hamilton, Ontario, Canada
,
Jack Hirsh
McMaster University and Hamilton Civic Hospitals Research Centre, Hamilton, Ontario, Canada
› Author Affiliations
Further Information

Publication History

Publication Date:
09 July 2018 (online)

  PDF Download  Permissions and Reprints
 

  • References

  • 1 Rosenberg RD. The heparin-antithrombin system: a natural anticoagulant mechanism. In: Colman RW, Hirsh J, Marder VJ, Salzman EW. (eds) Hemostasis and Thrombosis: Basic Principles and Clinical Practice. 3rd. ed. JB Lippincott; Philadelphia: 1994. pp 837-860
    Google Scholar
  • 2 Weitz JI, Hirsh J. New anticoagulant strategies. J Lab Clin Med 1993; 122: 364-373
    PubMedGoogle Scholar
  • 3 Hirsh J, Salzman EW, Marder VJ, Colman RW. Therapeutic agents and their practical use in thrombotic disorders: Approach to the thrombophilic patient for hemostasis and thrombosis. In: Colman RW, Hirsh J, Marder VJ, Salzman EW. (eds) Hemostasis and Thrombosis: Basic Principles and Clinical Practice. 3rd. ed. JB Lippincott; Philadelphia: 1994
    Google Scholar
  • 4 Harker LA, Gent M. Pathogenesis of arterial thrombosis. In Colman RW, Hirsh J, Marder VJ, Salzman EW. (eds) Hemostasis and Thrombosis: Basic Principles and Clinical Practice. 3rd. ed. JB Lippincott; Philadelphia: 1994
    Google Scholar
  • 5 Hirsh J. Heparin. N Engl J Med 1991; 324: 1565-1574
    CrossrefPubMedGoogle Scholar
  • 6 Hirsh J. Oral anticoagulant drugs. N Engl J Med 1991; 324: 1865-1875
    CrossrefPubMedGoogle Scholar
  • 7 Harker LA, Maraganore JM, Hirsh J. Novel antithrombotic agents. In: Colman RW, Hirsh J, Marder VJ, Salzman EW. (eds) Hemostasis and Thrombosis: Basic Principles and Clinical Practice. 3rd. ed. JB Lippincott; Philadelphia: 1994
    Google Scholar
  • 8 Levine M, Hirsh J, Gent M, Turpie AG G, Cruickshank M, Weitz J, Anderson D, Johnson M. A randomized trial comparing active thromboplastin time with heparin assay in patients with acute venous thromboembolism requiring large daily doses of heparin. Arch Int Med 1994; 154: 49-56
    CrossrefPubMedGoogle Scholar
  • 9 Hirsh J, Levine MN. Low molecular weight heparin. Blood 1992; 79: 1-17
    PubMedGoogle Scholar
  • 10 Weitz JI, Hudoba M, Massel D, Maraganore J, Hirsh J. Clot-bound thrombin is protected from inhibition by heparin-antithrombin III but is susceptible to inactivation by antithrombin Ill-independent inhibitors. J Clin Invest 1990; 86: 385-391
    CrossrefPubMedGoogle Scholar
  • 11 Markwardt F. Hirudin and derivatives as anticoagulant agents. Thromb Haemostas 1991; 66: 141-152
    PubMedGoogle Scholar
  • 12 Rydel TJ, Ravichandran KG, Tulinsky A. et al. The structure of a complex of recombinant hirudin and human α-thrombin. Science 1990; 249: 277-180
    CrossrefPubMedGoogle Scholar
  • 13 Maraganore JM, Chao B, Joseph ML, Jablonski J, Ramachandron KL. Anticoagulant activity of synthetic hirudin fragments. J Biol Chem 1989; 264: 8692-8698
    PubMedGoogle Scholar
  • 14 Maraganore JM, Bourdon P, Jablonski J, Ramachandron KL, Fenton II JW. Design and characterization of hirulogs: a novel class of bivalent peptide inhibitors of thrombin. Biochemistry 1990; 29: 7095-7801
    CrossrefPubMedGoogle Scholar
  • 15 Haskel EJ, Prager NA, Sobel BE, Abendschein DR. Relative efficacy of antithrombin compared with antiplatelet agents in accelerating coronary thrombolysis and preventing early reocclusion. Circulation 1991; 83: 1048-1056
    CrossrefPubMedGoogle Scholar
  • 16 Heras M, Chesebro JH, Penny WJ, Bailey KR, Badimon L, Fuster V. 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 1989; 79: 657-665
    CrossrefPubMedGoogle Scholar
  • 17 Klement P, Borm A, Hirsh J, Maraganore J, Wilson G, Weitz JI. The effect of thrombin inhibitors on tissue plasminogen activator induced thrombolysis in a rat model. Thromb Haemost 1992; 68: 64-68
    Article in Thieme ConnectPubMedGoogle Scholar
  • 18 Sitko GR, Ramjit DR, Stabilito II, Lehman D, Lynch JJ, Vlasuk GP. Conjunctive enhancement of enzymatic thrombolysis and prevention of thrombotic reocclusion with the selective Factor Xa inhibitor, tick anticoagulant peptide: comparison to hirudin and heparin in an animal model of acute coronary artery thrombosis. Circulation 1992; 85: 805-815
    CrossrefPubMedGoogle Scholar
  • 19 Agnelli G, Pascucci C, Cosmi B, Nenci GG. The comparative effects of recombinant hirudin (CGP 39393) and standard heparin on thrombus growth in rabbits. Thromb Haemost 1990; 63: 204-207
    Article in Thieme ConnectPubMedGoogle Scholar
  • 20 Agnelli G, Renga C, Weitz JI, Nenci GG, Hirsh J. Sustained antithrombotic activity of hirudin after its plasma clearance: Comparison with heparin. Blood 1992; 80: 960-965
    PubMedGoogle Scholar
  • 21 Kikumoto R, Tamao Y, Tesuka T, Tonomura S, Hara H, Ninomiya K, Hijikata A, Okamoto S. Selective inhibition of thrombin by (2R,4R)-4-methyl-1 [N2-[(3-methy 1-1,2,3,4-tetrahydro-8-quinoliny 1) sulfonyl]-L-arginyl)]-2-piperidinecarboxylic acid. Biochemistry 1984; 23: 85-90
    CrossrefPubMedGoogle Scholar
  • 22 Kettner C, Shaw E. D-Phe-Pro-ArgCH2Cl. A selective affinity label for thrombin. Thromb Res 1979; 14: 969-973
    CrossrefPubMedGoogle Scholar
  • 23 Bagdy D, Barabas E, Szabo G, Bajusz S, Szell E. In vivo anticoagulant and antiplatelet effect of D-Phe-Pro-Arg-H and D-MePhe-Pro-Arg-H. Thromb Haemost 1992; 67: 357-365
    Article in Thieme ConnectPubMedGoogle Scholar
  • 24 Krupski WC, Bass A, Kelly AB. et al. Heparin-resistant thrombus formation by endovascular stents in baboons: Interruption by a synthetic antithrombin. Circulation 1990; 82: 570
    CrossrefPubMedGoogle Scholar
  • 25 Kettner C, Mersinger L, Knabb R. The selective inhibition of thrombin by peptides of boroarginine. J Biol Chem 1990; 265: 18289
    PubMedGoogle Scholar
  • 26 Kotze H, Lumsden A, Harker LA. et al. In vivo antithrombotic effects of local vs systemic therapy with potent antithrombins (Abstract). Circulation 1990; 82 Suppl (Suppl. 03) 111-659
    PubMedGoogle Scholar
  • 27 Hanson SR, Harker LA. Interruption of acute platelet-dependent thrombosis by the synthetic antithrombin D-phenylalanyl-L-propyl-arginyl chloromethyl ketone. Proc Natl Acad Sci USA 1988; 85: 3184-3188
    CrossrefPubMedGoogle Scholar
  • 28 Lumsden AB, Kelly AB, Schneider PA. et al. Lasting safe interruption of endarterectomy thrombosis by transiently infused antithrombin peptide D-Phe-Pro-argCH2C 1 in baboons. Blood 1993; 81: 7
    PubMedGoogle Scholar
  • 29 Bagdy D, Barabas E, Szabo G. et al. In vivo anticoagulant and antiplatelet effect of D-Phe-Pro-Arg-H and D-MePhe-Pro-Arg-H. Thromb Haemost 1992; 67: 357
    Article in Thieme ConnectPubMedGoogle Scholar
  • 30 Markwardt F. Pharmacological approaches to thrombin regulation. Ann N Y Acad Sci 1986; 485: 204
    CrossrefPubMedGoogle Scholar
  • 31 Waxman L, Smith DE, Arcuri KE, Vlasuk GP. Tick anticoagulant peptide (TAP) is a novel inhibitor of blood coagulation factor Xa. Science 1990; 248: 593-596
    CrossrefPubMedGoogle Scholar
  • 32 Neeper MP, Waxman L, Smith DE, Schulman CA, Sardina M, Ellis RW, Schaffer LW, Siegl PK S, Vlasuk GP. Characterization of recombinant tick anticoagulant peptide. J Biol Chem 1990; 265: 17746-17752
    PubMedGoogle Scholar
  • 33 Dunwiddie CT, Thornberry N, Bull H, Sardana M, Friedman P, Jacobs J, Simpson E. Antistasin, a leech-derived inhibitor of factor Xa: Kinetic analysis of enzyme inhibition and identification of the reactive site. J Biol Chem 1989; 264: 16694-16699
    PubMedGoogle Scholar
  • 34 Nutt EM, Gasic T, Rodkey J, Gasic G, Jacobs J, Friedman P, Simpson E. The amino acid sequence of antistasin. J Biol Chem 1988; 263: 10162-10167
    PubMedGoogle Scholar
  • 35 Nutt EM, Jain D, Lenny A, Schaffer L, Siegl P, Dunwiddie CT. Purification and characterization of recombinant antistasin: A leech-derived inhibitor of coagulation factor Xa. Arch Biochem Biophy 1991; 285: 37-44
    CrossrefPubMedGoogle Scholar
  • 36 Tuszynski G, Gasic T, Gasic G. Isolation and characterization of antistasin. J Biol Chem 1987; 262: 9718-9723
    PubMedGoogle Scholar
  • 37 Dunwiddie CT, Nutt EM, Vlasuk GP, Siegel PK S, Schaffer LW. Anticoagulant efficacy and immunogenicity of the selective factor Xa inhibitor antistasin following subcutaneous administration in the Rhesus monkey. Thromb Haemost 1992; 67: 371-376
    Article in Thieme ConnectPubMedGoogle Scholar
  • 38 Vlasuk GP, Ramjit D, Fijita T, Dunwiddie CT, Nutt EM, Smith DE, Shebuski RJ. Comparison of the in vivo anticoagulant properties of standard heparin and the highly selective factor Xa inhibitors antistasin and tick anticoagulant peptide (TAP) in a rabbit model of venous thrombosis. Thromb Haemost 1991; 65: 257-262
    Article in Thieme ConnectPubMedGoogle Scholar
  • 39 Esmon CT. The roles of protein C and thrombomodulin in the regulation of blood coagulation. J Biol Chem 1989; 264: 4723
    PubMedGoogle Scholar
  • 40 Gruber A, Griffin JH, Harker LA, Hanson SR. Inhibition of platelet dependent thrombus formation by human activated protein C in a primate model. Blood 1989; 73: 639-642
    PubMedGoogle Scholar
  • 41 Gruber A, Hanson SR, Kelly AB, Yan BS, Bang N, Griffin JH, Harker LA. Inhibition of thrombus formation by activated recombinant protein C in a primate model of arterial thrombosis. Circulation 1990; 82: 578-585
    CrossrefPubMedGoogle Scholar
  • 42 Gruber A, Harker LA, Hanson SR, Kelly AB, Griffin JH. Anti-thrombotic effects of combining activated protein C and urokinase in nonhuman primates. Circulation 1991; 84: 2454-2464
    CrossrefPubMedGoogle Scholar
  • 43 Hanson SR, Kelly AB, Gruber A. et al. Antithrombotic efficacy and hemostatic safety of activated protein C in vivo. Advances Appl Biotech 1990; 11: 187
    PubMedGoogle Scholar
  • 44 Grinnell BW, Berg DT, Walls J, Yan SB. Trans-activated expression of fully gamma-carboxylated recombinant human protein C, an antithrombotic factor. Biotech 1987; 5: 1189-1192
    CrossrefPubMedGoogle Scholar
  • 45 Wu Q, Sheehan JP, Tsiang M. et al. Single amino acid substitutions dissociate fibrinogen-clotting and thrombomodulin-binding activities of human thrombin. Proc Nati Acad Sci USA 1991; 88: 6775
    CrossrefPubMedGoogle Scholar
  • 46 Weiss HJ, Turitto VT, Baumgartner HR, Nemerson Y, Hoffman T. Evidence for the presence of tissue factor activity on subendothelium. Blood 1989; 73: 968-975
    PubMedGoogle Scholar
  • 47 Wilcox JN, Smith KM, Schwartz SM, Gordon D. Localization of tissue factor in the normal vessel wall and in the atherosclerotic plaque. Proc Natl Acad Sci USA 1989; 86: 2839-2843
    CrossrefPubMedGoogle Scholar
  • 48 Zeldis SM, Nemerson Y, Pitlick FA, Lentz TL. Tissue factor (thromboplastin): Localization to plasma membranes by peroxidase-conjugated antibodies. Science 1972; 175: 766-768
    CrossrefPubMedGoogle Scholar
  • 49 Broze GJ, Warren LA, Novotny WF, Higuchi DA, Girard JJ, Miletich JP. The lipoprotein-associated coagulation inhibitor that inhibits the factor Vll-tissue factor complex also inhibits factor Xa: Insight into its possible mechanism of action. Blood 1988; 71: 335-343
    PubMedGoogle Scholar
  • 50 Rapaport SI. Inhibition of factor Vila/tissue factor-induced blood coagulation: With particular emphasis upon a factor Xa-dependent inhibitory mechanism. Blood 1989; 73: 359-365
    PubMedGoogle Scholar
  • 51 Haskel EJ, Torr SR, Day KC, Palmier MO, Wun T-C, Sobel BE, Abendschein DR. Prevention of arterial reocclusion after thrombolysis with recombinant lipoprotein-associated coagulation inhibitor. Circulation 1991; 84: 821-827
    CrossrefPubMedGoogle Scholar
  • 52 Cannon CP, McCabe CH, Henry TD, Rogers WJ, Schweiger M, Gibson RS, Anderson JL, Williams DO. Braunwald E for the TIMI 5 investigators: 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. JACC 1994; 23: 993-1003
    CrossrefPubMedGoogle Scholar
  • 53 The global use of strategies to open occluded coronary arteries (GUSTO) Ha investigators: Randomized trial of intravenous heparin versus recombinant Hirudin for acute coronary syndromes. Circulation 1994; 90: 1631-1637
    CrossrefPubMed
  • 54 Antman EM for the TIMI 9A investigators: Hirudin in acute myocardial infarction: a safety report from the thrombolysis and thrombin inhibition of in myocardial infarction (TIMI) 9A trial. Circulation 1994; 90: 1624-1630
    CrossrefPubMed
  • 55 Neuhaus KL, Essen Rv, Tebbe U, Jessel A, Heinrichs H. et al. Safety observations from the pilot phase of the randomized r-Hirudin for improvement of thrombolysis (HIT-HI) Study. Circulation 1994; 90: 1638-1642
    CrossrefPubMedGoogle Scholar
  • 56 Lidon RM, Theroux P, Lesperance J. et al. A pilot angiographic patency study using a direct thrombin inhibitor as adjunctive therapy to streptokinase in acute myocardial infarction. Circulation 1994; 89: 1567-1572
    CrossrefPubMedGoogle Scholar
  • 57 Topol AJ, Fuster V. et al. Recombinant hirudin for unstable angina: A multicenter, randomized angiographic trial subtitle. Circulation 1994; 89: 1-10
    CrossrefPubMedGoogle Scholar
  • 58 Gold HK, Torres FW, Garabedian HD, Werner W, Jang IK, Khan A, Hagstrom JN, Yasuda T, Leinbach RC, Newwell JB, Bovill EG, Stump DC, Collen D. Evidence for a rebound coagulation phenomenon after cessation of a 4-hour infusion of a specific thrombin inhibitor in patients with unstable angina pectoris. J Am Coll Cardiol 1993; 21: 1039-1047
    CrossrefPubMedGoogle Scholar
  • 59 Lidon RM, Theroux P, Juneau M, Adelman B, Maraganore J. Initial experience with a direct antithrombin, hirulog, in unstable angina: anticoagulant antithrombotic and clinical effects. Circulation 1993; 88: 1495-1501
    CrossrefPubMedGoogle Scholar
  • 60 Fuchs J, McCabe CH, Antman EM, Borzak S, Palisaitis D, Herson S. et al. Hirulog in the treatment of unstable angina: Results of the TIMI 7 trial. Circulation. 1995 in press
    PubMedGoogle Scholar
  • 61 Topol EJ, Bonan R, Jewitt D, Sigwart U, Kakkar VV, Rothman M. et al. Use of a direct antithrombin, hirulog, in place of heparin during coronary angioplasty. Circulation 1993; 87: 1622-1629
    CrossrefPubMedGoogle Scholar
  • 62 Eriksson BI, Kalebo P, Ekman S, Kerry R, Baur M, Bach D, Close P. Effective prevention of thromboembolic complications after total hip replacement with three different doses of recombinant hirudin, CGP 39393 (Revas-®), Ciba, compared to unfractionated heparin. Circulation 1994; 94: #3066
    PubMedGoogle Scholar
  • 63 Ginsberg J, Nurmohamed MT, Gent M, MacKinnon B, Sicurella J, Brill-Edwards P, Levine MN, Panju AA, Powers P, Stevens P, Turpie AG G. et al Use of hirulog in the prevention of venous thrombosis after major hip or knee surgery. Circulation 1994; 90: 2385-2389
    CrossrefPubMedGoogle Scholar