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Thromb Haemost 1999; 81(01): 26-31
DOI: 10.1055/s-0037-1614412
Review Article
Schattauer GmbH

Low Molecular Weight Heparin versus Acenocoumarol in the Secondary Prophylaxis of Deep Vein Thrombosis

S. Lopaciuk
,
H. Bielska-Falda
1   Institute of Hematology and Blood Transfusion, Warsaw, 1st Department of Surgery, Medical School, Warsaw
,
W. Noszczyk
1   Institute of Hematology and Blood Transfusion, Warsaw, 1st Department of Surgery, Medical School, Warsaw
,
M. Bielawiec
2   Department of Hematology, Medical School, Bialystok
,
W. Witkiewicz
3   Department of Vascular Surgery, District General Hospital, Wroclaw
,
S. Filipecki
4   Department of Internal Medicine, Institute of Tuberculosis and Lung Diseases, Warsaw
,
J. Michalak
5   Department of Vascular Surgery, Medical School, Lublin, 1st
,
L. Ciesielski
6   Department of Surgery, Medical School, Lodz
,
Z. Mackiewicz
7   Department of Vascular Surgery, Medical School, Bydgoszcz, 3rd
,
E. Czestochowska
8   Department of Internal Medicine, Medical School, Gdansk
,
K. Zawilska
9   Department of Hematology, Medical School, Poznan, District General Hospital, Krakow, Poland
,
A. Cencora
10   Department of Vascular Surgery, District General Hospital, Krakow, Poland
,
among others › Author Affiliations
Further Information

Publication History

Received11 June 1998

Accepted after resubmission22 September 1998

Publication Date:
08 December 2017 (online)

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Summary

The aim of this study was to determine the efficacy and safety of subcutaneous weight-adjusted dose low molecular weight heparin (LMWH) compared with oral anticoagulant (OA) in the prevention of recurrent venous thromboembolism. In a prospective multicenter trial, 202 patients with symptomatic proximal deep vein thrombosis (DVT) were included. As soon as the diagnosis of DVT was confirmed by phlebography, 101 were randomly assigned to receive LMWH (nadroparin) for secondary prophylaxis and 101 to receive OA (acenocoumarol). Patients in both groups were initially treated with nadroparin in a dose of 85 anti-Xa IU/kg s.c. every 12 h. Secondary prophylaxis with either nadroparin, 85 anti-Xa IU/kg s.c. once daily, or acenocoumarol was continued for at least 3 months. Three patients in the LMWH group and 6 in the OA group were excluded from analysis for various reasons. During the one-year combined secondary prophylaxis and surveillance period, 7 of of the 98 evaluable patients (7.1%) in the LMWH group and 9 of the 95 evaluable patients (9.5%) in the OA group had a documented recurrence of venous thromboembolism (Fisher ’s exact test, p = 0.61). Of these, 2 patients who received LMWH and 7 patients on acenocoumarol had recurrences in the 3-month period of secondary prophylaxis. Four patients (4.1%) in the LMWH group developed bleeding complications during this study period, as compared with 7 (7.4%) in the OA group (Fisher’s exact test, p = 0.37). There were two major bleedings, one in the LMWH group and one in the OA group. Eleven patients died, 5 (5.1%) in the LMWH group and 6 (6.3%) in the OA group. It is concluded that nadroparin in a dose of 85 anti-Xa IU/kg s.c. once daily provides an effective and safe alternative to oral anticoagulants in the secondary prophylaxis of DVT.

* *A list of other coauthors can be found in the Appendix on page 30.


 

  • References

  • 1 Hull R, Delmore T, Carter C, Hirsh J, Genton E, Gent M, Turpie G. Adjusted subcutaneous heparin versus warfarin sodium in the long-term treatment of venous thrombosis. N Engl J Med 1982; 306: 189-94.
    CrossrefPubMedSearch in Google Scholar
  • 2 Hall JG, Pauli RM, Wilson KM. Maternal and fetal sequelae of anticoagulation during pregnancy. Am J Med 1980; 68: 122-40.
    CrossrefPubMedSearch in Google Scholar
  • 3 Leizorowicz A, Haugh MC, Chapuis F-R, Samama MM, Boissel J-P. Low molecular weight heparin in prevention of perioperative thrombosis. Brit Med J 1992; 305: 913-20.
    CrossrefPubMedSearch in Google Scholar
  • 4 Green D, Hirsh J, Heit J, Prins M, Davidson B, Lensing AWA. Low molecular weight heparin: a critical analysis of clinical trials. Pharmacol Rev 1994; 46: 89-109.
    PubMedSearch in Google Scholar
  • 5 Bratt G, Aberg W, Johansson M, Törnebohm E, Granqvist S, Lockner D. Two daily subcutaneous injections of Fragmin as compared with intravenous standard heparin in the treatment of deep venous thrombosis (DVT). Thromb Haemost 1990; 64: 506-10.
    Thieme ConnectPubMedSearch in Google Scholar
  • 6 Duroux P, Beclere A. A randomised trial of subcutanoeus low molecular weight heparin (CY 216) compared with intravenous unfractionated heparin in the treatment of deep vein thrombosis. Thromb Haemost 1991; 65: 251-6.
    Thieme ConnectPubMedSearch in Google Scholar
  • 7 Hull RD, Raskob GE, Pineo GE, Green D, Trowbridge AA, Elliott CG, Lerner RG, Hall J, Sparling T, Brettell HR, Norton J, Carter CJ, George R, Merli G, Ward J, Mayo W, Rosenbloom D, Brant R. Subcutaneous low-molecular weight heparin compared with continuous intravenous heparin in the treatment of proximal-vein thrombosis. N Engl J Med 1992; 326: 975-82.
    CrossrefPubMedSearch in Google Scholar
  • 8 Prandoni P, Lensing AWA, Büller HR, Carta M, Cogo A, Vigo M, Casara D, Ruol A, ten Cate JW. Comparison of subcutaneous low-molecular weight heparin with intravenous standard heparin in proximal deep-vein thrombosis. Lancet 1992; 339: 441-5.
    CrossrefPubMedSearch in Google Scholar
  • 9 Lopaciuk S, Meissner AJ, Filipecki S, Zawilska K, Sowier J, Ciesielski L, Bielawiec M, Glowinski S, Czestochowska E. Subcutaneous low molecular weight heparin versus subcutaneous unfractionated heparin in the treatment of deep vein thrombosis: a Polish multicenter trial. Thromb Haemost 1992; 68: 14-8.
    Thieme ConnectPubMedSearch in Google Scholar
  • 10 Lindmarker P, Holmström M, Granquist S, Johnsson H, Lockner D. Comparison of once-daily subcutaneous Fragmin with continuous intravenous unfractionated heparin in the treatment of deep vein thrombosis. Thromb Haemost 1994; 72: 186-90.
    Thieme ConnectPubMedSearch in Google Scholar
  • 11 Koopman MMW, Prandoni P, Piovella F, Ockelford PA, Brandjes DPM, van der Meer J, Gallus AS, Simonneau G, Chesterman CH, Prins MH, Bossuyt PMM, de Haes H, van den Belt AGM, Sagnard L, d’Azemar P, Büller HR. for the TASSMAN Study Group. Treatment of venous thrombosis with intravenous unfractionated heparin administered in the hospital as compared with subcutaneous low-molecular-weight heparin administred at home. N Engl J Med 1996; 334: 682-7.
    CrossrefPubMedSearch in Google Scholar
  • 12 Levine M, Gent M, Hirsh J, Leclerc J, Anderson D, Weitz J, Ginsberg J, Turpie AG, Demers C, Kovacs M, Geerts W, Kassis J, Desjardins L, CuS-son J, Cruickhank M, Powers P, Brien W, Haley S, Willian A. 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: 677-81.
    CrossrefPubMedSearch in Google Scholar
  • 13 Simonneau G, Sors H, Charbonnier B, Page Y, Laaban J-P, Azarian R, Laurent M, Hirsch J-L, Ferrari E, Bosson J-L, Mottier D, Beau B. A comparison of low-molecular-weight heparin with unfractionated heparin for acute pulmonary embolism. N Engl J Med 1997; 337: 663-9.
    CrossrefPubMedSearch in Google Scholar
  • 14 The Columbus Investigators. Low-molecular-weight heparin in the treatment of patients with venous thromboembolism. N Engl Med 1997; 337: 657-62.
    CrossrefPubMedSearch in Google Scholar
  • 15 Hirsh J, Levine MN. Low molecular weight heparin. Blood 1992; 79: 1-17.
    PubMedSearch in Google Scholar
  • 16 Melissari E, Muray WJG, Das S, Wilson NV, Philip M, Kakkar VV. Does low molecular weight heparin have a role in the development of osteoporosis?. Thromb Haemost 1993; 69: 646
    PubMedSearch in Google Scholar
  • 17 Monreal M, Lafoz E, Olive A del Rio L, Vedia C. Comparison of subcutaneous unfractionated heparin with a low molecular weight heparin (Frag-min) in patients with venous thromboembolism and contraindications to coumarin. Thromb Haemost 1994; 71: 7-11.
    Thieme ConnectPubMedSearch in Google Scholar
  • 18 Lensing AW, Hirsh J, Büller HR. Diagnosis of Venous Thrombosis. In: Hemostasis and Thrombosis. Basic Principles and Clinical Practice. Colman RW, Hirsh J, Marder VJ, Salzman EW. eds. Philadelphia: J. B. Lippincott; 1993: 1297-321.
    Search in Google Scholar
  • 19 Hirsh J, Hoak J. Management of deep vein thrombosis and pulmonary embolism. Circulation 1996; 93: 2212-45.
    CrossrefPubMedSearch in Google Scholar
  • 20 Hirsh J, Bettman M, Coates G, Hull RD. Diagnosis of Pulmonary Embolism. In: Hemostasis and Thrombosis. Basic Principles and Clinical Practice. Colman RW, Hirsh J, Marder VJ, Salzman EW. eds. Philadelphia: J. B. Lippincott; 1993: 1322-30.
    Search in Google Scholar
  • 21 Griffiths E, Dzik WH. Assays for heparin-induced thrombocytopenia. Transfusion Med 1997; 7: 1-11.
    CrossrefPubMedSearch in Google Scholar
  • 22 Hull R, Hirsh J, Carter C, England C, Gent M, Turpie AGG, McLoughlin D, Dodd P, Thomas M, Raskob G, Ockelford P. Different intensities of oral anticoagulant therapy in the treatment of proximal-vein thrombosis. N Engl J Med 1982; 307: 1676-81.
    CrossrefPubMedSearch in Google Scholar
  • 23 Holmgren K, Andersson G, Fagrell B, Johnsson H, Ljungberg B, Nilsson E, Wilhelmsson S, Zetterquist S. One-month versus six-month therapy with oral anticoagulants after symptomatic deep vein thrombosis. Acta Med Scand 1985; 218: 279-84.
    PubMedSearch in Google Scholar
  • 24 Pini M, Alello S, Manotti C, Pattacini C, Quintavalla R, Poli T, Tagliaferri A, Dettori AG. Low molecular weight heparin versus warfarin in the prevention of recurrences after deep vein thrombosis. Thromb Haemost 1994; 72: 191-7.
    Thieme ConnectPubMedSearch in Google Scholar
  • 25 Das SK, Cohen AT, Edmondson RA, Melissari E, Kakkar VV. Low-molecular-weight heparin versus warfarin for prevention of recurrent venous thromboembolism: a randomized trial. Word J Surg 1996; 20: 521-7.
    CrossrefPubMedSearch in Google Scholar
  • 26 Hirsh J, Fuster V. Guide to anticoagulant therapy. Part 1: Heparin. Circulation 1994; 89: 1449-68.
    CrossrefPubMedSearch in Google Scholar
  • 27 Kirchmaier CM, Lindhoff-Last E, Rübesam D, Scharrer I, Vigh Zs, Mosch G, Wolf H, Breddin HK. Regression of deep vein thrombosis by i.v.-administration of a low molecular weight heparin – results af a pilot study. Thromb Res 1994; 73: 337-48.
    CrossrefPubMedSearch in Google Scholar
  • 28 Green D, Hull RD, Brant R, Pineo GF. Lower mortality in cancer patients treated with low-molecular-weight heparin versus standard heparin. Lancet 1992; 339: 1476
    PubMedSearch in Google Scholar
  • 29 Schulman S, Rhedin A-S, Lindmarker P, Carlsson A, Lärfars G, Nicol P, Loogna E, Svensson E, Ljungberg B, Walter H, Viering S, Nordlander S, Leijd B, Jonsson K-A, Hjorth M, Linder O, Boberg J. A comparison of six weeks with six months of oral anticoagulant therapy after a first episode of venous thromboembolism. N Engl J Med 1995; 332: 1661-5.
    CrossrefPubMedSearch in Google Scholar
  • 30 Levine MN, Hirsh J, Gent M, Turpie AG, Weitz J, Ginsberg J, Geerts W, LeClerc J, Neemeh J, Powers P. Optimal duration of oral anticoagulant therapy: a randomized trial comparing four weeks with three months of warfarin in patients with proximal deep vein thrombosis. Thromb Haemost 1995; 74: 606-11.
    Thieme ConnectPubMedSearch in Google Scholar
  • 31 Prandoni P, Lensing AWA, Cogo A, Cuppini S, Villalta S, Carta M, Cattelan AM, Polistena P, Bernardi E, Prins M.H. The long-term clinical course of acute deep venous thrombosis. Ann Intern Med 1996; 125: 1-7.
    CrossrefPubMedSearch in Google Scholar
  • 32 Prandoni P, Lensing AW, Büller HR, Cogo A, Prins MH, Cattelan AM, Cuppini S, Noventa F, ten Cate JW. Deep-vein thrombosis and the incidence of subsequent cancer. N Engl J Med 1992; 327: 1128-33.
    CrossrefPubMedSearch in Google Scholar