Thromb Haemost 1994; 72(02): 186-190
DOI: 10.1055/s-0038-1648836
Original Article
Schattauer GmbH Stuttgart

Comparison of Once-Daily Subcutaneous Fragmin® with Continuous Intravenous Unfractionated Heparin in the Treatment of Deep Vein Thrombosis

Per Lindmarker
1   The Department of Medicine, Karolinska University Hospital, Swedan
,
Margareta Holmström
2   The Department of Medicine, Huddinge University Hospital, Stockholm, Sweden
,
Staffan Granqvist
3   The Department of Radiology, Huddinge University Hospital, Stockholm, Sweden
,
Hans Johnsson
1   The Department of Medicine, Karolinska University Hospital, Swedan
,
Dieter Lockner
2   The Department of Medicine, Huddinge University Hospital, Stockholm, Sweden
› Author Affiliations
Further Information

Publication History

Received 06 December 1993

Accepted after resubmission 31 March 1994

Publication Date:
24 July 2018 (online)

Summary

Two hundred and four consecutive patients with venographically confirmed deep vein thrombosis (DVT) were randomised either to a low molecular weight heparin, Fragmin®, administered subcutaneously (s.c.) once daily as a fixed dose of 200IU anti-factor Xa/kg or to continuous intravenous infusion of unfractionated heparin (UFH). The UFH dose was adjusted to maintain the activated partial thromboplastin time between 1.5 and 3.0 times the upper limit of the reference value at each centre. Fragmin® or UFH was given for a minimum of 5 days until anticoagulation with warfarin, given from day 1, was established (i. e. an International Normalised Ratio, of 2.0−3.0). A second venogram was obtained after Fragmin® or UFH treatment. There were no significant differences in the change in mean Marder score before and after treatment between the two treatment groups, irrespective of thrombus localisation. No major bleeding events, symptomatic pulmonary embolism, symptomatic thrombosis progression or death occurred during hospitalisation. Eight documented venous thromboembolic events occurred before the follow-up visit 6 months after randomisation: 5 in patients treated with Fragmin® and 3 in those treated with UFH. Six of these events occurred after cessation of warfarin treatment. In conclusion Fragmin® given s.c. once daily in a fixed dose adjusted for body weight, is no less effective or safe than a continuous infusion of UFH in the initial treatment of acute DVT.

 
  • References

  • 1 Bratt G, Tömebohm E, Granquist S, Åberg W, Lockner D. A comparison between low molecular weight heparin (KABI2165) and standard heparin in the treatment of deep venous thrombosis. Thromb Haemost 1985; 54: 813-817
  • 2 Holm HA, Ly B, Handeland GF, Abildgaard U, Amesen KE, Gottschalk P, Høeg V, Aandahl M, Haugen K, Laerum F, Scheel B, Sortland O, Vinje B. Subcutaneous heparin treatment of deep venous thrombosis with low molecular weight heparin. Haemostasis 1986; 16 Suppl (Suppl. 02) 30-37
  • 3 Faivre R, Neuhart Y, Kieffer Y, Apfel F, Magnin D, Didier D, Toulemond F, Bassand JP, Maurat JP. Un nouveau traitement de thromboses veineuses profondes: les fractions d’héparine de bas poids moléculaire. Presse Med 1988; 17: 197-200
  • 4 Bratt G, Åberg W, Johansson M, Tömebohm E, Granquist S, Lockner D. Two daily subcutaneous injections of Fragmin® as compared with intravenous standard heparin in the treatment of deep venous thrombosis. Thromb Haemost 1990; 64: 506-510
  • 5 Duroux P, Beclere A. A randomised trial of subcutaneous low molecular weight heparin (CY216) compared with intravenous unfractionated heparin in the treatment of deep vein thrombosis: a collaborative European multicentre study. Thromb Haemost 1991; 3: 251-256
  • 6 Prandoni P, Lensing AW, Büller HR, Carta M, Cogo A, Vigo M, Casara D, Ruol A, Ten Cate JW. Comparison of subcutaneous low-molecular weight heparin with standard heparin in proximal deep-vein thrombosis. Lancet 1992; 339: 441-445
  • 7 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: 14-18
  • 8 Hull RD, Raskob GE, Pineo GF, 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 heparin compared with continuous intravenous heparin in the treatment of proximal-vein thrombosis. N Engl J Med 1992; 326: 975-982
  • 9 Simonneau G, Charbonnier B, Descousus H, Planchon B, Ninet J, Sie P, Silsiguen M, Combe S. 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
  • 10 Lensing AW, Prins M, Koopman M, Büller H. Which heparin for proximal deep-vein thrombosis. (letter) Lancet 1992; 340: 311-312
  • 11 Hirsh J, Levine MN. Low molecular weight heparin. Blood 1992; 79: 1-17
  • 12 Hull RD, Pineo GF. Therapeutic use of low-molecular-weight heparins. Haemostasis 1993; 23 Suppl (Suppl. 01) 1-9
  • 13 Lockner D, Bratt G, Tömebohm E, Åberg W. Pharmacokinetics of intravenously and subcutaneously administered Fragmin in healthy volunteers. Haemostasis 1986; 16 Suppl (Suppl. 02) 8-10
  • 14 Bergqvist D, Hedner U, Sjörin E, Holmer E. Anticoagulant effects of two types of low molecular weight heparin administered subcutaneously. Thromb Res 1983; 32: 381-391
  • 15 Bratt G, Tömebohm E, Widlund L, Lockner D. Low molecular weight heparin (KABI 2165, Fragmin): pharmacokinetics after intravenous and subcutaneous administration in human volunteers. Thromb Res 1986; 42: 613-620
  • 16 Marder VJ, Soulen RL, Atichartakarn VM, Budzynski AZ, Parulekar S, Kim JR, Edvard N, Zahavi J, Algazy KM. Quantitative venographic assessment of deep vein thrombosis in the evaluation of streptokinase and heparin therapy. J Lab Clin Med 1977; 89: 1018-1029
  • 17 Holmström M, Berglund M-C, Granquist S, Bratt G, Tömebohm E, Lockner D. Fragmin® once or twice daily subcutaneously in the treatment of deep venous thrombosis of the leg. Thromb Res 1992; 67: 49-55
  • 18 Rabinov K, Paulin S. Roentgen diagnosis of venous thrombosis in the leg. Arch Surg 1972; 104: 134-144
  • 19 The PIOPED investigators. Value of the ventilation/perfusion scan in acute pulmonary embolism: results of the Prospective Investigation of Pulmonary Embolism Diagnosis (PIOPED). JAMA 1990; 263: 2753-2759
  • 20 Holm HA, Abildgaard U, Kalvenes S, Anderssen N, Ankler E, Amesen K-E, Blikom D, Drivenes A. The Antithrombotic Effect of Heparin in Deep Venous Thrombosis; Relation to Four Heparin Assays. Acta Med Scand 1984; 216: 287-293
  • 21 Holmgreen K, Jacobsson H, Johnsson H, Ljungberg B, Löfsjögård-Nilsson E. Thermography and pletysmography, a non-invasive alternative to venography in the diagnosis of deep vein thrombosis. J Int Med 1990; 228: 29-33
  • 22 Albada J, Nieuwenhuis HK, Sixma JJ. Treatment of acute venous thromboembolism with low molecular weight heparin (Fragmin®). Circulation 1989; 80: 935-940
  • 23 Handeland GF, Abildgaard U, Holm HA, Amesen K-E. 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