Semin Thromb Hemost 2001; 27(5): 543-550
DOI: 10.1055/s-2001-17965
Copyright © 2001 by Thieme Medical Publishers, Inc., 333 Seventh Avenue, New York, NY 10001, USA. Tel.: +1(212) 584-4662

Hirudins for Prophylaxis and Treatment of Venous Thromboembolism

Domenico Prisco, Michela Falciani, Emilia Antonucci, Gian Franco Gensini
  • University of Florence, Florence, Italy
Further Information

Publication History

Publication Date:
22 October 2001 (online)

ABSTRACT

At present, unfractionated heparin (UFH) and low molecular weight heparins (LMWHs) are used extensively for the prophylaxis and treatment of venous thromboembolism (VTE) and in most cases represent the agents of choice for these indications. However, both UFH and LMWHs have biophysical limitations. Over the past years, the progress in molecular biology and biotechnology has stimulated growing interest in hirudin, the most potent known natural inhibitor of thrombin. The biological properties of hirudin combined with its ready availability as recombinant forms make this drug well-suited for use as an anticoagulant agent. Available studies indicate that hirudin is significantly more effective for prophylaxis of VTE after total hip replacement than is either UFH or enoxaparin. Only limited data are available on its efficacy in the treatment of deep vein thrombosis. Moreover, hirudin is effective in the management of patients with heparin-induced thrombocytopenia (HIT) who require further anticoagulation. In conclusion, hirudin is an antithrombotic drug of high quality and may represent an attractive alternative to UFH and LMWHs in the management of VTE, and it is among the agents of choice in patients with contraindications to heparin therapy (such as HIT patients).

REFERENCES

  • 1 Hirsh J, Warkentin T E, Raschke R. Heparin and low-molecular-weight heparin: mechanisms of action, pharmacokinetics, dosing considerations, monitoring, efficacy and safety.  Chest . 1998;  114 489S-510S
  • 2 Markwardt F. The development of hirudin as an antithrombotic drug. In: Pifarré R, ed. New Anticoagulants for the Cardiovascular Patient Philadelphia: Hanley & Belfus 1997: 145-160
  • 3 Agnelli G, Sonaglia F. Clinical status of direct thrombin inhibitors.  Crit Rev Oncol Hematol . 1999;  31 97-117
  • 4 Fareed J, Walenga J M, Iyer L, Hoppensteadt D, Pifarré R. An objective perspective on recombinant hirudin: a new anticoagulant and antithrombotic agent.  Blood Coagul Fibrinolysis . 1991;  2 135-147
  • 5 Haycraft J B. On the action of secretion obtained from the medicinal leech on the coagulation of the blood.  Proc R Soc Lond . 1884;  36 478-487
  • 6 Callas D D, Hoppensteadt D, Fareed J. Comparative studies on the anticoagulant and protease generation inhibitory actions of newly developed site-directed thrombin inhibitory drugs: efegatran, argatroban, hirulog, and hirudin.  Semin Thromb Hemost . 1995;  21 177-183
  • 7 Markwardt F, Kaiser B, Nowak G. Studies on antithrombotic effects of recombinant hirudin.  Thromb Res . 1989;  54 377-388
  • 8 Agnelli G, Pascucci C, Cosmi B, Nenci G G. The comparative effects of recombinant hirudin (CGP 39393) and standard heparin on thrombus growth in rabbits.  Thromb Haemost . 1990;  63 204-207
  • 9 Heras M, Chesebro J H, Webster M W. Hirudin, heparin and placebo during deep arterial injury in the pig. The in vivo role of thrombin in platelet-mediated thrombosis.  Circulation . 1990;  82 1476-1484
  • 10 Kaiser B, Simon A, Markwardt F. Antithrombotic effects of recombinant hirudin in experimental angioplasty and intravascular thrombolysis.  Thromb Haemost . 1990;  63 44-47
  • 11 Agnelli G, Renga C, Weitz J I, Nenci G G, Hirsh J. Sustained antithrombotic activity of hirudin after its plasma clearance: comparison with heparin.  Blood . 1992;  80 960-965
  • 12 Freund M, Cazenave J P, Courtney M. Inhibition by recombinant hirudins of experimental venous thrombosis and disseminated intravascular coagulation induced by tissue factor in rats.  Thromb Haemost . 1990;  63 187-192
  • 13 Gray E, Watton J, Cesmeli S, Barrowcliffe T W, Thomas D P. Experimental studies on a recombinant hirudin, CGP 39393.  Thromb Haemost . 1991;  65 355-359
  • 14 Talbot M. Biology of recombinant hirudin (CGP 39393): a new prospect in the treatment of thrombosis.  Semin Thromb Hemost . 1989;  15 293-301
  • 15 Verstraete M, Nurmohamed M, Kienast J. Biologic effects of recombinant hirudin (CGP 39393) in human volunteers. European Hirudin in Thrombosis Group.  J Am Coll Cardiol . 1993;  22 1080-1088
  • 16 Rao A K, Sun L, Chesebro J H. Distinct effects of recombinant desulfatohirudin (Revasc) and heparin on plasma levels of fibrinopeptide A and prothrombin fragment F1.2 in unstable angina: a multicenter trial.  Circulation . 1996;  94 2389-2395
  • 17 Cofrancesco E, Cortellaro M, Leonardi P. Markers of hemostatic system activation during thromboprophylaxis with recombinant hirudin in total hip replacement.  Thromb Haemost . 1996;  75 407-411
  • 18 Topol E J, Fuster V, Harrington R A. Recombinant hirudin for unstable angina pectoris: a multicenter, randomized angiographic trial.  Circulation . 1994;  89 1557-1566
  • 19 Marbet G A, Verstraete M, Kienast J. Clinical pharmacology of intravenously administered desulfatohirudin (CGP 39393) in healthy volunteers.  J Cardiovasc Pharmacol . 1993;  22 364-372
  • 20 Nowak G, Bucha E. A new method for therapeutical monitoring of hirudin.  Thromb Haemost . 1993;  69 1306(Abst)
  • 21 Clagett G P, Anderson Jr A F, Geerts W. Prevention of VTE.  Chest . 1998;  114(Suppl 5) 531S-560S
  • 22 Eriksson B I, Kalebo P, Ekman S. Direct thrombin inhibition with rec-hirudin CGP 39393 as prophylaxis of thromboembolic complications after total hip replacement.  Thromb Haemost . 1994;  72 227-231
  • 23 Eriksson B I, Ekman S, Kalebo P. Prevention of deep-vein thrombosis after total hip replacement: direct thrombin inhibition with recombinant hirudin, CGP 39393.  Lancet . 1996;  347 635-639
  • 24 Eriksson B I, Ekman S, Lindbratt S. Prevention of thromboembolism with use of recombinant hirudin. Results of a double-blind, multicenter trial comparing the efficacy of desirudin (Revasc) with that of unfractionated heparin in patients having a total hip replacement.  J Bone Joint Surg Am . 1997;  79 326-333
  • 25 Eriksson B I, Wille-Jorgensen P, Kalebo P. A comparison of recombinant hirudin with a low-molecular-weight heparin to prevent thromboembolic complications after total hip replacement.  N Engl J Med . 1997;  337 1329-1335
  • 26 Levin L A, Horst M, Bergqvist D. Economic evaluation of desirudin vs heparin in deep vein thrombosis prevention after hip replacement surgery.  Pharmacoeconomics . 1998;  13 111-118
  • 27 Zeymer U. Recombinant hirudins: an overview of recent developments.  Biodrugs . 1998;  10 425-436
  • 28 Adkins J C, Wilde M I. Lepirudin: a review of its potential place in the management of thrombotic disorders.  Biodrugs . 1998;  10 227-255
  • 29 Ginsberg J S, Nurmohamed M T, Gent M. Use of hirulog in the prevention of venous thrombosis after major hip or knee surgery.  Circulation . 1994;  90 2385-2389
  • 30 Parent F, Bridey F, Dreyfus M. Treatment of severe venous thromboembolism with intravenous hirudin (HBW 023): an open pilot study.  Thromb Haemost . 1993;  70 386-388
  • 31 Schiele F, Vuillemenot A, Kramarz P H. A pilot study of subcutaneous recombinant hirudin (HBW 023) in the treatment of deep vein thrombosis.  Thromb Haemost . 1994;  71 558-562
  • 32 Ginsberg J S, Nurmohamed M T, Gent M. Effects on thrombin generation of single injections of hirulogTM in patients with calf vein thrombosis.  Thromb Haemost . 1994;  72 523-525
  • 33 Schiele F, Lindgaerde F, Eriksson H. Subcutaneous recombinant hirudin (HBW 023) versus intravenous sodium heparin in treatment of established acute deep vein thrombosis of the legs: a multicenter prospective dose-ranging randomized trial.  Thromb Haemost . 1997;  77 834-838
  • 34 Warkentin T E, Levine M N, Hirsh J. Heparin-induced thrombocytopenia in patients treated with low-molecular-weight heparin or unfractionated heparin.  N Engl J Med . 1995;  332 1330-1335
  • 35 Schmitt B P, Adelman B. Heparin-associated thrombocytopenia: a critical review and a pooled analysis.  Am J Med Sci . 1993;  305 208-215
  • 36 Warkentin T E, Chong B E, Greinacher A. Heparin-induced thrombocytopenia: towards consensus.  Thromb Haemost . 1998;  79 1-7
  • 37 Chong B H. Heparin-induced thrombocytopenia.  Br J Haematol . 1995;  89 431-439
  • 38 Slaughter T F, Greenberg C S. Heparin-associated thrombocytopenia and thrombosis: implications for perioperative management.  Anesthesiology . 1997;  87 667-675
  • 39 Schiele F, Vuillemenot A, Kramarz P. Use of recombinant hirudin as antithrombotic treatment in patients with heparin-induced thrombocytopenia.  Am J Hematol . 1995;  50 20-25
  • 40 Greinacher A, Volpel H, Pötzsch B. Recombinant hirudin in the treatment of patients with heparin-induced thrombocytopenia.  Blood . 1996;  88(Suppl 1) 281(Abst)
  • 41 Greinacher A, Eichler P, Lubenow N, Kwasny H, Luz M. Heparin-induced thrombocytopenia with thromboembolic complications: meta-analysis of 2 prospective trials to assess the value of parenteral treatment with lepirudin and its therapeutic aPTT range.  Blood . 2000;  96 846-851
  • 42 Huhle G, Hoffmann U, Hoffmann I. A new therapeutic option by subcutaneous recombinant hirudin in patients with heparin-induced thrombocytopenia type II: a pilot study.  Thromb Res . 2000;  99 325-334