Once-daily Subcutaneous Dalteparin, a Low Molecular Weight Heparin, for the Initial Treatment of Acute Deep Vein Thrombosis

Summary

The aim of the study was to compare the efficacy and safety of once-daily subcutaneous injection of dalteparin, a low molecular weight heparin, with that of intravenous unfractionated heparin in the treatment of deep venous thrombosis (DVT). Patients were included if they had deep venous thrombosis distal to inguinal ligament and were randomised either before, if it was considered necessary, or after phlebographic verification of the diagnosis. There was no pre-inclusion treatment with unfractionated heparin. One hundred and twenty patients received dalteparin, administered subcutaneously once-daily at a fixed dose of 200 IU anti-factor Xa/kg, and 133 patients received a continuous intravenous infusion of unfractionated heparin (UFH). Oral anticoagulation was started on the first or second day, and initial treatment with dalteparin or UFH discontinued when the prothrombin time was in the therapeutic range (2<INR<3) on two consecutive days. Control phlebograms were taken within 4 days, thereafter. There were no significant differences between the two initial treatment groups in improvements in Marder score. Two major bleeding events occurred in the UFH group versus none in the dalteparin group. One patient in each group experienced clinically significant pulmonary embolism. During a mean follow-up period of 6.9 ± 1.5 months, recurrent DVT occurred in four patients in the dalteparin group and in two of the UFH group. These results confirm those of a previous study on dalteparin in the initial treatment of DVT, and suggest that dalteparin administered once-daily at a fixed dose of 200 UI/kg is as effective and well-tolerated as UFH in patients with DVT below the inguinal ligament. The present study also demonstrates that dalteparin can be started as soon as the diagnosis of DVT is suspected and without pre-treatment with UFH. Given that the administration of once-daily subcutaneous injections needs not require a patient to be hospitalised, studies to investigate the possibility of using dalteparin for the initial treatment of DVT in the outpatient setting are warranted.

• References

• 1 Holm HA, Ly B, Handeland GF, Abildgaard U, Amesen KE, Gottschalk P, Hoeg V, Aandahl M, Haugen K, Loerum F, Scheel B, Sortland O, Vinje B. Subcutaneous heparin treatment of deep venous thrombosis: a comparison of unfractionated and low molecular weight heparin. Haemostasis 16 (Suppl. 02) 30-37
• 2 Faivre R, Neuhart Y, Kieffer Y, Apfel F, Magnin D, Didier D, Toulemonde F, Bassand JP, Maurat JP. A new treatment of deep venous thrombosis: low molecular weight heparin fractions. Randomized study. Presse Med 1988; 17 (05) 197-200
• 3 Bratt G, Aberg W, Tomebohm E, Granqvist S, Lockner D. Subcutaneous Kabi 2165 in the treatment of deep venous thrombosis (DVT) of the leg. Thromb Res 1987; VII: 24 (abstract)
• 4 Bratt G, Aberg W, Tomebohm E, Johansson M, 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: 506-510
• 5 Lensing AWA, Prins MH, Davidson BL, Hirsh J. Treatment of deep venous thrombosis with low-molecular-weight heparins. Arch Intern Med 1995; 155: 601-607
• 6 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: 441-451
• 7 Leizorovicz A, Simonneau G, Decousus H, Boissel JP. Comparison of efficacy and safety of low molecular weight heparins and unfractionated heparin in initial treatment of deep venous thrombosis: a meta-analysis. Br Med J 1994; 309: 299-304
• 8 Hull RD, Raskob GE, Pineo GF, Green D, Trowbridge AA, Elliott CG, Lemer RG, Hall J, Sparling T, Brettell HR, Norton J, Carter CJ, George R, Merli G, Ward J, Mayo W, Rosenblomm 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: 975-982
• 9 Holmström M, Berglund MC, Granquist S, Bratt G, Tomebohm 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
• 10 Lindmarker P, Holmström M, Granqvist 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: 186-190
• 11 Etude Multicentrique. Traitement des thromboses veineuses profondes constitutes. Etude comparative d’un fragment d’heparine de bas poids moleculaire (Fragmine®) administre par voie sous-cutanee et de 1’heparine standard administree par voie intraveineuse continue. Rev Med Interne 1989; 10: 375-381
• 12 A collaborative European multicenter study. A randomised 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
• 13 Simonneau G, Charbonnier B, Decousus H, Planchon B, Ninet J, Sié P, Silsiguen M, Combe S. Subcutanous 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
• 14 Marder VJ, Soulen RL, Atichartakam V, Budzynski AZ, Parulekar S, Kim JR, Edward 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
• 15 Alhenc-Gelas M, Jestin-Le GuemicC, Vitoux JF, Kher A, Aiach M, Fiessinger JN. for the Fragmin-Study group Adjusted versus fixed doses of the low-molecular-weight heparin Fragmin® in the treatment of deep vein thrombosis. Thromb Haemost 1994; 71: 698-702