Interní Med. 2004; 6(9): 442-449

Nízkomolekulární hepariny

prof. MUDr. Jaroslav Malý CSc
I. interní klinika Fakultní nemocnice v Hradci Králové

Keywords: low molecular weight heparin, vein and arterial thrombosis.

Published: December 31, 2004  Show citation

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Malý J. Nízkomolekulární hepariny. Interní Med. 2004;6(9):442-449.

Antitrombotická aktivita nízkomolekulárních heparinů (LMWH) v podkožním podání vytváří antitrombotické prostředí více mechanizmy:

a) významně se váže na antitrombin a tím selektivněji inhibuje faktor Xa

b) zvyšuje fibrinolýzu

c) snižuje inhibitor aktivátoru plazminogenu (PAI)

d) zvyšuje inhibitor tkáňového faktoru a tím inhibuje tkáňový faktor a zevní koagulační systém.

LMWH jsou standardizovány podle inhibiční aktivity k faktoru Xa. Preparáty s vyšší aktivitou anti Xa však nemají prokazatelně větší antitrombotický efekt. LMWH se používá v mnoha odvětvích medicíny. Oproti nefrakcionovanému heparinu jej lze s výhodou použít v transplantologii, v léčbě a prevenci cévních uzávěrů u nádorových chorob, u nemocných s tromboembolismy v cerebrální oblasti, v profylaxi a léčbě hlubokých žilních trombóz u nemocných s ischemickou chorobou srdeční. LMWH specificky blokuje receptor hladkých svalových vláken (SMC receptor) a tím brání jejich proliferaci, čehož se využívá u nemocných po koronárních angioplastikách.

Low molecular weight heparins

Antithrombotic activity of low molecular weight heparins (LMWH) in subcutaneous application creates antithrombotic environment by several mechanisms:

a) binds significantly to antithrombin, thus inhibits factor Xa more selectively

b) increases fibrinolysis

c) decreases a plasminogen activator inhibitor (PAI)

d) increases tissue factor inhibitor, thus inhibits tissue factor and extrinsic coagulation system.

LMWH are standardized according to the inhibition activity of factor Xa. However, preparations with higher anti Xa activity don-t have demonstrably greater antithrombotic effect. LMWH is used in many branches of medicine. In comparison to an unfractionated heparin it is used with an advantage in transplant medicine, in a treatment and prevention of vascular occlusions in tumours, in patients with thromboembolisms in cerebral area, in a prophylaxis and treatment of deep vein thrombosis in patients with ischaemic heart disease. LMWH expressly blocks a receptor of smooth muscle fibres (SMC receptor) thus interferes with their proliferation, which is used in patients following coronary angioplasty.

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    References

    1. Agnelli G, Sonaglia F. Prevention of venous thrombosis.,Thrombosis Res 2000; 97: V49-62. Go to original source... Go to PubMed...
    2. American College of Chest Physicians. Sixth ACCP Consensus Conference on Antithrombotic Therapy. Chest 2001; 119, Suppl.: 1-48.
    3. Andrew M, Brooker LA, Ginsberg JS, Kelton JG. Clinical problems in anticoagulation therapy. Hematology, Education program. Am Soc Hematol 1997; 8-28.
    4. Beer HJ, Burger M, Gretener S, et al. Outpatient treatment of pulmonary embolism is feasible and safe in a substantial proportion of patients. J Thromb Haemost 2003; 1: 186-187. Go to original source... Go to PubMed...
    5. Bates SM, Ginsberg JS. Thrombosis in pregnancy. Current Opinion in Hematology 1997; 4: 335-343. Go to original source... Go to PubMed...
    6. Bates SM, Hirsh J. Treatment of venous thromboembolism. Thromb Haemostas 1999; 82: 870-877. Go to original source... Go to PubMed...
    7. Bergquist D, Benmoni G, Björgell O, et al. LMWH (enoxaparin) as prophylaxis against venous thromboembolism after total hip replacement. N Engl J Med 1996; 335: 696-700. Go to original source... Go to PubMed...
    8. Bijsterveld NR, Peters RJ, Murphy SA, Bernink PJ, Tijssen JG, Cohen M. Recurrent cardiac ischemic events early after discontinuation of short-term heparin treatment in acute coronary syndromes: results from the Thrombolysis in Myocardial Infarction (TIMI) 11B and Efficacy and Safety of Subcutaneous Enoxaparin in Non-Q-Wave Coronary Events (ESSENCE) studies.J Am Coll Cardiol. 2003,42(12):2083-2089. Go to original source... Go to PubMed...
    9. Breddin HK, Hach-Wunderle V, Nakov R, Kakkar VV, for the CORTES Investigators. Effects of a low molecular weight heparin on thrombus regression and recurrent thromboembolism in patients with deep vein thrombosis. N Engl J Med 2001; 344: 626-631. Go to original source... Go to PubMed...
    10. Brill-Edwards P, Ginsberg JS, Git M, et al. for the Recurrence of Clot in this Pregnancy Study Group.: Safety of withholding heparin in pregnant women with a history of venous thromboembolism. N Engl J Med 2000; 343: 1439-1444. Go to original source... Go to PubMed...
    11. Büller H, TenCate JW. Primary venous thromboembolism and cancer screening. Editorial. N Engl J Med 1998; 338: 1221-1222. Go to original source... Go to PubMed...
    12. Cohen M, Antman EM, Gurfinkel EP, Radley D. ESSENCE (Efficacy and Safety of Subcutaneous Enoxaparin in Non-Q-wave Coronary Events) and TIMI (Thrombolysis in Myocardial Infarction) 11B Investigators. Enoxaparin in unstable angina/non-ST-segment elevation myocardial infarction: treatment benefits in prespecified subgroups. J Thromb Thrombolysis. 2001 Dec; 12(3): 199-206. Go to original source... Go to PubMed...
    13. Collins R, Scrimgeour A, Yusuf S, Peto R. Reduction of fatal pulmonary embolism and venous thrombosis by perioperative administration of subcutaneous heparin. Overview of results and randomized trials in general, orthopaedic and urologic surgery. N Engl J Med 1988; 318: 1162-1173. Go to original source... Go to PubMed...
    14. Dahl OE, Andreassen G, Aspelin T, et al. Prolonged thromboprophylaxis following hip replacement surgery. Results of a double blind, prospective, randomised, placebo-controlled study with dalteparin (Fragmin). Thromb Haemostat 1997; 77: 26-31. Go to original source... Go to PubMed...
    15. Dolovich LR, Ginsberg JS, Douketis JD, et al. A meta-analysis comparing low-molecular-weight heparins with unfractionated heparin in the treatment of venous thromboembolism. Examining some unaswered questions regarding location of treatment, product type, and dosing frequency. Arch Intern Med 2000; 160: 181-188. Go to original source... Go to PubMed...
    16. Durica SS. Venous thromboembolism in cancer patient. Current Opinion in Hematology 1997; 4: 306-311. Go to original source... Go to PubMed...
    17. Fareed J, Hoppensteadt D, Walenga JM, et al. A perspective of low molecular weight heparins in the management of thrombosis, Hamostaseologie 1993; 13: S5-S11. Go to original source...
    18. Fraisse F, Holzapfel I, Coulaud JM, et al. Nadroparin in the prevention of deep vein thrombosis in acute decompensated COPD. Am J Respir Crit Care Med 2000; 161: 1109-1114. Go to original source... Go to PubMed...
    19. Ginsberg JS, Greer I, Hirsh J.Use of antithrombotic agents during pregnancy. Chest 2001; 119: 122S-131S. Go to original source... Go to PubMed...
    20. Gould MK, Dembitzer AD, Doyle RL, et al. 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. Go to original source... Go to PubMed...
    21. Heit JA, Berkowitz SD, Bona R, et al. Efficacy and safety of low molecular weight heparin (ardeparin sodium) compared to warfarin for prevention of venous thromboembolism following total knee replacement. A double blind dose-ranging study. Thromb Haemostat 1997; 77: 32-38. Go to original source...
    22. Hirsh J, Warkentin TE, Shaughnessy SG, et al. Heparin and low molecular weight heparin. Chest 2001; 119: 64S-94S. Go to original source... Go to PubMed...
    23. Hirsh J. Comparison of the relative efficacy and safety of low molecular weight heparin and unfractionated heparin for the treatment of deep venous thrombosis. Seminars in Hematology 1997; 34, Suppl. 4: 20-25. Go to original source...
    24. Hull RD, Pineo GF, Stein PD, et al. Timing of initial administration of low-molecular-weight heparin prophylaxis against deep vein thrombosis in patients following elective hip arthroplasty. Arch Intern Med 2001; 161: 1952-1960. Go to original source... Go to PubMed...
    25. Hull RD, Raskob GE, Brant RF, et al. Low-molecular-weight heparin vs heparin in the treatment of patients with pulmonary embolism. American-Canadian Thrombosis Study Group. Arch Intern Med 2000; 160: 229-236. Go to original source... Go to PubMed...
    26. Hull RD, Pineo GF, Raskob GE. The economic impact of treating deep vein thrombosis with low-molecular-weight haperin: outcome of therapy and health economy aspects. Haemostasis 1998; 28, Suppl. 3: 8-16. Go to original source... Go to PubMed...
    27. Hyers TM, Agnelli G, Hull RD, et al. Antithrombotic therapy for venous thromboembolic International Consensus Statement. Prevention of venous thromboembolism. Guidelines compiled in accordance with the scientific evidence. Intern Angiol 2001; 20: 1-37. Go to original source...
    28. Korkmaz ME. Low-molecular-weight heparins in acute coronary syndromes. Curr Vasc Pharmacol. 2003 Oct; 1(3): 259-271. Go to original source... Go to PubMed...
    29. Kovacs MJ, Anderson D, Morrow B, et al. Outpatient treatment of pulmonary embolism with dalteparin. Thromb Haemost 2000; 83: 209-211. Go to original source... Go to PubMed...
    30. Lee AY, Levine MN, Baker RI, Bowden C, Kakkar AK, Prins M, Rickles FR, Julian JA, Haley S, Kovacs MJ, Gent M. Randomized Comparison of Low-Molecular-Weight Heparin versus Oral Anticoagulant Therapy for the Prevention of Recurrent Venous Thromboembolism in Patients with Cancer (CLOT) Investigators. N.Engl J Med. 2003; 349(2):109-111. Go to original source... Go to PubMed...
    31. Levine M. Treatment of Thrombotic Disorders in Cancer Patients, Haemostasis 1997; 27, Suppl.1.: 38-43. Go to original source... Go to PubMed...
    32. Levine M, Gent M, Hirsh J, et al. 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. Go to original source... Go to PubMed...
    33. Meyer G, Brenot F, Pacouret G, et al. Subcutaneous low-molecular-weight heparin fragmin versus intravenous unfractionated heaprin in the treatment of acute non massive pulmonary embolism: an open randomised pilot study. Thromb Haemostat 1995; 74: 1432-1435. Go to original source...
    34. Savage KJ, Wells PS, Schulz V, et al. Outpatient use of low molecular weight heparin (Dalteparin) for the treatment of deep vein thrombosis of the upper extremity. Thromb. Haemost. 1999; 82: 1008-1010. Go to original source... Go to PubMed...
    35. Shaughnessy SG, Hirsh J, Bhandari M, et al. A histomorphometric evaluation of heparin induces bone loss after discontinuation of heparin treatment in rats. Blood 1999; 93: 1231-1236. Go to original source...
    36. Schwartz DR, Malhotra A, Weinberger SE. Venous thromboembolism in pregnancy. In: UpToDate, Rose BD. (Ed.), UpToDate, Wellesley, MA, 2000, 1989; 172: 99-103.
    37. Spinler SA, Inverso SM, Cohen M, Goodman SG, Stringer KA, Antman EM. ESSENCE and TIMI 11B Investigators. Safety and efficacy of unfractionated heparin versus enoxaparin in patients who are obese and patients with severe renal impairment: analysis from the ESSENCE and TIMI 11B studies. Am Heart J. 2003 Jul; 146(1): 33-41. Go to original source... Go to PubMed...
    38. Task Force Report. Task Force on Pulmonary Embolism, European Society of Cardiology. Guidelines on diagnosis and management of acute pulmonary embolism. Eur. Heart J. 2000; 21: 1301-1336. Go to original source... Go to PubMed...
    39. The Columbus Investigators. Low molecular heparin in the treatment of patients with venous thromboembolism. N. Engl. J. Med. 1997; 337: 657-662. Go to original source... Go to PubMed...
    40. Théry C, Simonneau G, Meyer G, et al. Randomized trial of subcutaneous low-molecular-weight heparin CY 216 (fraxiparin) compared with intravenous unfractionated heparin in the curative treatment of submassive pulmonary embolism. A dose-ranging study. Circulation 1992; 85: 1380-1389. Go to original source... Go to PubMed...
    41. Toglia MR, Wog JG. Venous thromboembolism during pregnancy. N. Engl. J. Med. 1996; 335: 108-114. Go to original source... Go to PubMed...
    42. Turpie AG. Choice of low molecular weight heparins. J Thromb Haemost. 2003; 1: 598. Go to original source... Go to PubMed...
    43. Turpie AG, Antman EM. Low-molecular-weight heparins in the treatment of acute coronary syndromes. Arch Intern Med. 2001 Jun 25; 161(12): 1484-1490. Go to original source... Go to PubMed...
    44. Turpie AGG, Norris TM. Thromboprophylaxix in medical patients, the role of low-molecular-weight heparin., Thromb. Haemostas 2004; 92: 3-12. Go to original source...
    45. Wells PS, Kovacs MJ, Forgie MA, et al. Expanding eligibility for outpatient treatment of deep venous thrombosis and pulmonary embolism with low molecular weight heparin: A comparison of patient self-injection to home care injection. Arch. Intern. Med. 1998; 158: 1809-1812. Go to original source... Go to PubMed...
    46. Widimský J, Malý J. Akutní plicní embolie a žilní trombóza, Nakl. Triton 2002: 304 s.

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