Advertisement

Low molecular weight heparins — Pharmacological principles and indications in clinical practice

  • J. Harenberg
Chapter
  • 87 Downloads

Summary

The pharmacological effects of low molecular weight heparins are characterized by an increased inhibition of factor Xa and decreased inhibition of thrombin of the coagulation cascade in comparison to unfractionated heparins. After administration into the circulation blood, levels are sustained twice as long as for unfractionated heparin on factor Xa inhibition leading to a biological half-life of 2 h after intravenous administration and of 4 h after subcutaneous administration. The clearance of LMW heparins is decreased and the area under the activity time curve is increased more than 2-fold compared to unfractionated heparin. The effects on bleeding time and hemorrhage are decreased in animal models.

In postoperative medicine LMW heparins once daily (o. d.) have a higher efficacy as low dose unfractionated heparin three times daily (t. e. d.). In medical bedridden hospitalized patients LMW heparin o. d. is as effective and probably safer than unfractionated heparin t. e. d. Heparin-induced thrombocytopenia type II occurs less frequently. Treatment of recent deep venous thrombosis is performed more effectively and safely using low molecular weight heparins. So far, there is no sufficient evidence for different efficacies of LMW heparins in these indications. The efficacy and safety of low molecular weight heparins is currently proven in patients with cerebral ischaemia and unstable angina.

Key words

Low molecular weight heparin prophylaxis of thromboembolism heparin-induced thrombocytopenia cerebral ischaemia unstable angina 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Bergmann JF, Neuhart E (1996) A multicentric randomized double-blind study of enoxaparin compared with unfractionated heparin in the prevention of venous thromboembolism disease in elderly in-patients bedridden for an acute medical illness. Thromb Haemostas 76: 529–534Google Scholar
  2. 2.
    Bergqvist D, Benoni G, Björgell O, Fredin H, Hedlundi U, Nicolas S, Nilsson P, Nylander G (1996) Low-molecular-weight heparin (Enoxaparin) as prophylaxis against venous thromboembolism after total hip replacement. N Engl J Med 335:696–700PubMedCrossRefGoogle Scholar
  3. 3.
    Dahl OE, Andreasson G, Aspelin T, Müller C, Mathiesen P, Nyhus S, Abdelnoor M, Solhaug JH, Arnesen H (1997) Prolonged thromboprophylaxis following hip replacement surgery — Results of a double-blind, prospective, randomised, placebo-controlled study with Dalteparin (Fragmin®). Thromb Haemostas 77: 26–31Google Scholar
  4. 4.
    Fiessinger JN, Charbonnier BA, Sixma JJ, Wenzel E (1997) Comparison of once daily with a twice daily subcutaneous nadroparin calcium regimen in the treatment of deep vein thrombosis. The FRAXODY study. Thromb Haemost suppl: 1582, AbstrGoogle Scholar
  5. 5.
    Harenberg J, Huhle G, Piazolo L, Giese CH, Heene DL (1997) Long-term anticoagulation of outpatients with adverse events to oral anticoagulants using low-molecular-weight heparin. Semin Thromb Hemost 23: 167–172PubMedCrossRefGoogle Scholar
  6. 6.
    Harenberg J, Roebruck P, Heene DL on behalf of the Heparin Study in Internal Medicine Group (1996) Subcutaneous low-molecular-weight heparin versus standard heparin and the prevention of thromboembolism in medical inpatients. Haemostasis 26:127–139PubMedGoogle Scholar
  7. 7.
    Harenberg J, Schmitz-Huebner U (1997) Therapie der Beinvenenthrombose mit niedermolekularen Heparinen. Dtsch Ärztebl 94: 2257–2260Google Scholar
  8. 8.
    Harenberg J, Schmitz-Huebner U, Breddin K, Haas S, Heinrich F, Heinrichs CH, Kienast J, Roebruck P, Theiss W, Wenzel E (1997) Treatment of deep vein thrombosis with low-molecularweight heparins: A consensus statement of the Gesellschaft für Thrombose-und Hämostaseforschung (GTH). Semin Thromb Hemost 23: 91–96PubMedCrossRefGoogle Scholar
  9. 9.
    Harenberg J, Siegele M, Dempfle CE, Stehle G, Heene DL (1993) Protamine neutralization of the release of tissue factor pathway inhibitor activity by heparins. Thromb Haemostas 70: 942–943Google Scholar
  10. 10.
    Harenberg J, Stehle G, Augustin J, Zimmermann R (1989) Comparative human pharmacology of low molecular weight heparins. Semin Thromb Hemost 15:414–423PubMedCrossRefGoogle Scholar
  11. 11.
    Kay R, Wons SW, Yu YL, Chan YW, Tsoi TH, Ahuja AT, Chan FL, Fong KY, Law CB, Wong A, Woo J (1995) Low-molecular-weight heparin for the treatment of acute ischaemic stroke. N Engl J Med 333:1588–1593PubMedCrossRefGoogle Scholar
  12. 12.
    Kock HJ, Schmit-Neuerburg KP, Hanke J, Rudofsky G, Hirche H (1995) Thromboprophylaxis with low-molecular-weight heparin in outpatients with plaster-cast immobilization of the leg. Lancet 346:459–461PubMedCrossRefGoogle Scholar
  13. 13.
    Koopman MMW, Prandoni P, Piovella F, Ockfort PA, Brandjes DP, Van der Meer J, Gallus AS, Simonneau G, Chesterman CH, Prins MH et al. (1996) Treatment of patients with proximalvein thrombosis with intravenous unfractionated heparin in hospital compared with subcutaneous low-molecular-weight heparin out of hospital or with early discharge. N Engl J Med 334: 682–687PubMedCrossRefGoogle Scholar
  14. 14.
    Kujath P, Spannagel U, Habscheid W, Schindler G, Weckbach A (1992) Thrombosis prevention in outpatients with lower limb injuries. Dtsch Med Wochenschr 117:6–10PubMedCrossRefGoogle Scholar
  15. 15.
    Lechler E, Schramm W, Flosbach CW (1996) The venous thrombotic profile of a low-molecular-weight heparin (enoxaparin). The Prime Study Group. Haemostasis 26(suppl. 2): 49–56PubMedGoogle Scholar
  16. 16.
    Levine M, Gent M, Hirsh J, Leclerc J, Anderson D, Weitz J, Ginsberg JS, Turpie AG, Demers C, Kovacs M (1996) A comparison of low-molecular-weight heparin administered primarily at home with unfractionated heparin administered in the hospital for proximal deepvein-thrombosis. N Engl J Med 334:677–681PubMedCrossRefGoogle Scholar
  17. 17.
    Monreal M, Lafoz E, Olive S, del Rio L, Vedia C (1994) Comparison of subcutaneous unfractionated heparin with a low molecular weight heparin (Fragmin) in patients with venous thromboembolism and contraindications to coumarin. Thromb Haemostas 71: 7–11Google Scholar
  18. 18.
    Nurmohamed MT, Rosendaal FR, Büller HR, Dekker E, Hommes DW, Vanderbroucke JP, Briet (1992) Low molecular weight heparin versus standard heparin in general and orthopaedic surgery: a meta-analysis. Lancet 340:152–156PubMedCrossRefGoogle Scholar
  19. 19.
    Pini M, Manotti C, Pattacini C, Quintavalla R, Poli T, Tagliaferri A, Dettori AG (1994) Low molecular weight heparin versus warfarin in the prevention of recurrences after deep vein thrombosis. Thromb Haemostas 72:191–197Google Scholar
  20. 20.
    Planes A, Vochelle N, Darmon Y, Fagola M, Bellaud M, Huet Y (1996) Risk of deep-venous thrombosis after hospital discharge in patients having undergone total hip replacement: Double-blind randomised comparison of enoxaparin versus placebo. Lancet 348:224–228.PubMedCrossRefGoogle Scholar
  21. 21.
    Racanelli A, Fareed J (1992) Ex vivo activity of heparin is not predictive of blood loss after neutralization by protamine. Thromb Res 67:263–273PubMedCrossRefGoogle Scholar
  22. 22.
    Reilmann H, Weinberg AM, Forster EE, Happe B (1993) Thromboseprophylaxe bei ambulanten Patienten. Orthopäde 22:117–120PubMedGoogle Scholar
  23. 23.
    Spiro TE (1997) A multicenter clinical trial comparing once and twice-daily subcutaneous enoxaparin and intravenous heparin in the treatment of acute deep vein thrombosis. Thromb Haemost 1997; suppl: 1527, Abstr.Google Scholar
  24. 24.
    Charbonnier BA, Fiessinger JN, Banga JD, Wenzel E, d’Azemar P, Sagnard L. Thromb Haemost (1998) Comparison of a once daily with a twice daily subcutaneous how molecular weight heparin regimen in the treatment of deep vein therombosis 79:897–901PubMedGoogle Scholar
  25. 25.
    Warkentin TH, Levine MN, Hirsh J, Horsewood P, Roberts RS, Gent M, Kelton JG (1995) Heparin-induced thrombocytopenia in patients treated with low molecular weight heparin or unfractionated heparin. N Engl J Med 332:1330–1335PubMedCrossRefGoogle Scholar
  26. 26.
    Zagrodnick J, Kaufner HK (1990) Ambulante Thromboembolie-prophylaxe in der Traumatologie durch Selbstinjektion von Heparin. Unfallchirurg 93:331–333.PubMedGoogle Scholar

Copyright information

© Dr. Dietrich Steinkopff Verlag GmbH & Co. KG, Darmstadt 2000

Authors and Affiliations

  • J. Harenberg
    • 1
  1. 1.I. Dept. of Medicine, Faculty of Clinical Medicine MannheimUniversity of HeidelbergMannheimGermany

Personalised recommendations