Semin Respir Crit Care Med 2000; 21(6): 533-540
DOI: 10.1055/s-2000-13191
Copyright © 2000 by Thieme Medical Publishers, Inc., 333 Seventh Avenue, New York, NY 10001, USA. Tel.: +1(212) 584-4662

Treatment of Acute Deep Venous Thrombosis and Pulmonary Embolism: Use of Low Molecular Weight Heparin

Victor F. Tapson
  • Division of Pulmonary and Critical Care Medicine, Duke University Medical Center, Durham, North Carolina
Further Information

Publication History

Publication Date:
31 December 2000 (online)

ABSTRACT

Over the past decade, the use of low molecular weight heparin (LMWH) preparations has revolutionized the approach to preventing and treating venous thromboembolism. For established deep venous thrombosis, numerous prospective clinical trials have indicated that these drugs are at least as safe and as effective as standard, unfractionated heparin (UFH) and perhaps even more effective at preventing recurrences. Advantages of low molecular weight heparin include superior bioavailability compared with standard heparin, once- or twice-daily subcutaneous delivery, and the lack of need to monitor in most clinical circumstances. Because of these advantages, increasing numbers of stable, compliant patients with deep venous thrombosis are being treated as outpatients. This approach requires an organized team effort with comprehensive patient education and carefully planned follow-up. Cost-benefit analyses have unequivocally proved that when treatment with low molecular weight heparin is utilized in the outpatient setting, there are substantial cost savings.

REFERENCES

  • 1 Hyers T M, Agnelli G, Hull R D. Antithrombotic therapy for venous thromboembolic disease. Fifth American College of Chest Physicians Consensus Conference.  Chest . 1998;  114 561S-578S
  • 2 Hirsh J, Dalen J E, Deykin D, Poller L. Heparin: mechanism of action, pharmacokinetics, dosing considerations, monitoring, efficacy and safety.  Chest . 1992;  102(Suppl) 337-351
  • 3 Lagerstedt C I, Olsson C-G, Fagher B O, Oqvist B W. Need for long-term anticoagulant treatment in symptomatic calf-vein thrombosis.  Lancet . 1985;  2 515-518
  • 4 Moser K M, LeMoine J R. Is embolic risk conditioned by location of deep venous thrombosis?.  Ann Intern Med . 1981;  94 439-444
  • 5 Raschke R A, Reilly B M, Guidry J R. The weight-based heparin dosing nomogram compared with a ``standard care'' nomogram.  Ann Intern Med . 1993;  199 874
  • 6 Hull R D, Raskob G E, Hirsh J. Continuous intravenous heparin compared with intermittent subcutaneous heparin in the initial treatment of proximal vein thrombosis.  N Engl J Med . 1986;  315 1109-1114
  • 7 Hull R, Raskob G, Rosenbloom D. Optimal therapeutic level of heparin therapy in patients with venous thrombosis.  Arch Intern Med . 1992;  152 1589-1595
  • 8 Sanson B J, Lensing A W, Prins M H. Safety of low-molecular-weight heparin in pregnancy: a systematic review.  Thromb Haemost . 1999;  81 668-672
  • 9 Linhardt R J, Gunay N S. Production and chemical processing of low molecular weight heparins.  Semin Thromb Hemost . 1999;  25 5-16
  • 10 Nader H B, Walenga J M, Berkowitz S D. Preclinical differentiation of low molecular weight heparins.  Semin Thromb Hemost . 1999;  25 63-72
  • 11 A Collaborative European Multicentre Study. A randomized trial of subcutaneous low molecular weight heparin (CY 216) compared with intravenous unfractionated heparin in the treatment of deep vein thrombosis.  Thromb Haemost . 1991;  65 251-256
  • 12 Albada J, Nieuwenhuis H K, Sixma J J. Treatment of acute venous thromboembolism with low molecular weight heparin (Fragmin): results of a double-blind randomized study.  Circulation . 1989;  80 935-940
  • 13 Bratt G, Aberg W, Johansson M. Two daily subcutaneous injections of Fragmin as compared with intravenous standard heparin in the treatment of deep venous thrombosis (DVT).  Thromb Haemost . 1990;  64 506-510
  • 14 Bratt G, Tornebohm E, Granqvist S. A comparison between low molecular weight heparin (KABI 2165) and standard heparin in the intravenous treatment of deep venous thrombosis.  Thromb Haemost . 1985;  54 813-817
  • 15 Holm H A, Ly B, Handeland G F. Subcutaneous heparin treatment of deep venous thrombosis: a comparison of unfractionated and low molecular weight heparin.  Haemostasis . 1986;  16 30-37
  • 16 Prandoni P, Vigo M, Cattelan A M. Treatment of deep venous thrombosis by fixed doses of a low-molecular-weight heparin (CY216).  Haemostasis . 1990;  20(Suppl 1) 220-330
  • 17 Simonneau G, Charbonnier B, Decousus H. Subcutaneous low molecular weight heparin compared with continuous intravenous unfractionated heparin in the treatment of proximal deep vein thrombosis.  Arch Intern Med . 1993;  153 1541-1546
  • 18 Handeland G F, Abildgaard U, Holm H A. Dose adjusted heparin treatment of deep venous thrombosis: a comparison of unfractionated and low molecular weight heparin.  Eur J Clin Pharmacol . 1990;  39 107-112
  • 19 Harenberg J, Huck K, Bratsch H. Therapeutic application of subcutaneous low-molecular-weight heparin in acute venous thrombosis.  Haemostasis . 1990;  20(Suppl 1) 205-219
  • 20 Huet Y, Janvier G, Bendriss P H. Treatment of established venous thromboembolism with enoxaparin: preliminary report.  Acta Chir Scand . 1990;  556(Suppl) 116-120
  • 21 Prandoni P, Lensing A WA, Buller H R. Comparison of subcutaneous low molecular weight heparin with intravenous standard heparin in proximal vein thrombosis.  Lancet . 1992;  339 441-445
  • 22 Hull R D, Raskob G E, Pineo G F. Subcutaneous low-molecular-weight heparin compared with continuous intravenous heparin in the initial treatment of proximal-vein thrombosis.  N Engl J Med . 1992;  326 975-982
  • 23 Lopaciuk S, Meissner A J, Filipecki S. Subcutaneous low molecular weight versus subcutaneous unfractionated heparin in the treatment of deep vein thrombosis: a Polish multicenter trial.  Throm Haemost . 1992;  68 14-18
  • 24 Lindmarker P, Holmstrom M, Granqvist S. Comparison of once-daily subcutaneous Fragmin with continuous intravenous unfractionated heparin in the treatment of deep vein thrombosis.  Thromb Haemost . 1994;  72 186-190
  • 25 Fiessinger J N, Lopez-Fernandez M, Gatterer E. Once-daily subcutaneous dalteparin, a low molecular weight heparin, for the initial treatment of acute deep vein thrombosis.  Thromb Haemost . 1996;  76 195-199
  • 26 Luomanmaki K, Granqvist S, Hallert C. A multicentre comparison of once-daily subcutaneous dalteparin (low molecular weight heparin) and continuous intravenous heparin in the treatment of deep vein thrombosis.  J Intern Med . 1996;  240 85-92
  • 27 Kirrchmaier C M, Wolf H, Scheafer H. Efficacy of a low molecular weight heparin administered intravenously or subcutaneously in comparison with intravenous unfractionated heparin in the treatment of deep venous thrombosis. Certoparin Study Group.  Int Angiol . 1998;  17 135-145
  • 28 Siragusa S, Cosmi B, Piovella F, Hirsh J, Ginsberg J S. Low-molecular-weight heparins and unfractionated heparin in the treatment of patients with acute venous thromboembolism: results of a meta-analysis.  Am J Med . 1996;  100 269-277
  • 29 Lensing A WA, Prins M H, Davidson B L, Hirsh J. Treatment of deep venous thrombosis with low-molecular-weight heparins: a meta-analysis.  Arch Intern Med . 1995;  155 601-607
  • 30 Leizorovicz A, Simonneau G, Decousus H, Boissel J P. Comparison of efficacy and safety of low molecular weight heparins and unfractionated heparin in initial treatment of deep venous thrombosis.  BMJ . 1994;  309 299-304
  • 31 Gould M K, Dembitzer A D, Doyle R L. Low-molecular-weight heparins compared with unfractionated heparin for treatment of acute deep venous thrombosis. A meta-analysis of randomized, controlled trials.  Ann Intern Med . 1999;  130 800-809
  • 32 Dolovich L R, Ginsberg J S, Douketis J D. A meta-analysis comparing low-molecular-weight heparins with unfractionated heparin in the treatment of venous thromboembolism: examining some unanswered questions regarding location of treatment, product type, and dosing frequency.  Arch Intern Med . 2000;  160 181-188
  • 33 Simonneau G, Sors H, Charbonnier B. A comparison of low-molecular-weight heparin with unfractionated heparin for acute pulmonary embolism. The THESEE Study Group.  N Engl J Med . 1997;  337 663-669
  • 34 The Columbus Investigators. Low molecular-weight heparin in the treatment of patients with venous thromboembolism.  N Engl J Med . 1997;  337 657-662
  • 35 Meyer G, Brenot F, Pacouret G. Subcutaneous low-molecular-weight heparin Fragmin versus intravenous unfractionated heparin in the treatment of acute non massive pulmonary embolism: an open randomized pilot study.  Thromb Haemost . 1995;  74 1432-1435
  • 36 Kovacs M J, Anderson D, Morrow B. Outpatient treatment of PE with dalteparin.  Thromb Haemost . 2000;  83 209-211
  • 37 Levine M, Gent M, Hirsh J. A comparison of low molecular-weight-heparin administered primarily at home with unfractionated heparin administered in the hospital for proximal deep vein thrombosis.  N Engl J Med . 1996;  334 677-681
  • 38 Koopman M M, Prandoni P, Piovella F. Low molecular-weight-heparin versus heparin for proximal deep vein thrombosis.  N Engl J Med . 1996;  334 682-687
  • 39 O'Brien B, Levine M, Willan A. Economic evaluation of outpatient treatment with low-molecular-weight heparin for proximal vein thrombosis.  Arch Intern Med . 1999;  159 2298-2304
  • 40 Gould M K, Dembitzer A D, Sanders G D. Low-molecular-weight heparin compared with unfactionated heparin for treatment of acute DVT: a cost-effectiveness analysis.  Ann Intern Med . 1999;  130 789-799
  • 41 Hull R D, Raskob G E, Rosenbloom D. Treatment of proximal vein thrombosis with subcutaneous low-molecular weight heparin vs. intravenous heparin: an economic perspective.  Arch Intern Med . 1997;  157 289-294
  • 42 Kearon C, Gent M, Hirsh J. A comparison of three months of anticoagulation with extended anticoagulation for a first episode of idiopathic venous thromboembolism.  N Engl J Med . 1999;  340 901-907
  • 43 Hettiarachchi R J, Prins M H, Lensing A W. Low molecular weight heparin versus unfractionated heparin in the initial treatment of venous thromboembolism.  Curr Opin Pulm Med . 1998;  4 220-225
  • 44 Hettiarachchi R J, Smorenburg S M, Ginsberg J. Do heparins do more than just treat thrombosis?.  <~>The influence of heparins on cancer spread. Thromb Haemost . 1999;  82 947-952
  • 45 Kakkar A K, Williamson R C. Prevention of venous thromboembolism in cancer patients.  Semin Thromb Hemost . 1999;  25 239-243
  • 46 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
  • 47 Tapson V F, Hull R. Management of venous thromboembolic disease: the impact of low-molecular-weight heparin.  Clin Chest Med . 1995;  16 281-294