Thromb Haemost 1994; 71(05): 698-702
DOI: 10.1055/s-0038-1642507
Review Article
Schattauer GmbH Stuttgart

Adjusted Versus Fixed Doses of the Low-Molecular-Weight Heparin Fragmin in the Treatment of Deep Vein Thrombosis

M Alhenc-Gelas
1   Laboratoire d’Hémostase, Hôpital Broussais, Paris
,
C Jestin-Le Guernic
2   Laboratoires Kabi, St. Quentin en Yvelines, Hôpital Broussais, France
,
J F Vitoux
3   Centre Claude Bernard de Recherche sur les Maladies Vasculaires, Service de Médecine Vasculaire, Hôpital Broussais, France
,
A Kher
2   Laboratoires Kabi, St. Quentin en Yvelines, Hôpital Broussais, France
,
M Aiach
1   Laboratoire d’Hémostase, Hôpital Broussais, Paris
,
J N Fiessinger
3   Centre Claude Bernard de Recherche sur les Maladies Vasculaires, Service de Médecine Vasculaire, Hôpital Broussais, France
,
Fragmin-Study Group › Institutsangaben
Weitere Informationen

Publikationsverlauf

Received: 17. September 1993

Accepted after revision 06. Februar 1994

Publikationsdatum:
06. Juli 2018 (online)

Summary

Treatment monitoring based on a laboratory parameter increases the efficacy and safety of standard heparin therapy, but it is not known if this also applies to low-molecular-weight heparin (LMWH) therapy of acute deep vein thrombosis (DVT). In a prospective randomized trial involving 122 consecutive patients, group A (58 patients) received a weight adjusted dose of Fragmin (100 IU/kg) subcutaneously twice a day throughout the treatment period (10 days ± 1), while in group B (64 patients) the dosage was based on the results of an anti factor Xa (anti Xa) amidolytic assay to obtain a target concentration from 0.5 to 1 IU/ml. AntiXa and antithrombin activities were also measured retrospectively on frozen plasma from all patients. The two regimens were comparable in terms of hemorrhagic complications (4 in group A and 3 in group B). Bilateral ascending phlebography was performed before inclusion and at the end of LMWH treatment. Treatment efficacy, based on Marder’s score, did not differ between the two groups (p = 0.3). Dosage adjustment to between 0.5 to 1IU anti-Xa/ml does not therefore appear to improve the efficacy or safety of LMWH tieatment. However, correlations between the change in Marder’s score and both anti-Xa (p <0.001) and antithrombin activity (p <0.001) were observed, suggesting a relationship between the degree of FXa or thrombin inhibition and antithrombotic activity.

 
  • References

  • 1 Hirsh J. Heparin. N Engl J Med 1991; 324: 1565-74
  • 2 Hull RD, Raskob GE, Rosenbloom D, Lemaire J, Pineo GF, Baylis B, Ginsberg JS, Panju AA, Brilledwards P, Brant R. Optimal therapeutic level of heparin therapy in patients with venous thrombosis. Arch Intern Med 1992; 152: 1589-95
  • 3 Vitoux JF, Aiach M, Roncato M, Fiessinger JN. Should thromboprophylactic dosage of low molecular weight heparin be adapted to patient’s weight?. Thromb Haemost 1988; 59: 120
  • 4 Bratt G, Törnebohm E, Granqvist S, Aberg W, Lockner D. A comparison between low molecular weight heparin (Kabi 2165) and standard heparin in the intravenous treatment of deep venous thrombosis. Thromb haemost 1985; 54: 813-7
  • 5 Holm HA, Handeland GF, Abildgaard U, Arnesen KE, Gottschalk P, Heg 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 moleculai weight heparin. Haemostasis 1986; 16 Suppl (Suppl. 02) 30-7
  • 6 Alhnda I, Nicuwcnhuis HK, Sixma JJ. Treatment of acute venous thromboembolism with low molecular weight heparin (Fragmin). Results of a double-blind randomized study. Circulation 1989; 80: 935-40
  • 7 Bratt G, Aherg W, Johansson M, Tornebohm 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
  • 8 Etude multicentrique. Traitement des thromboses veineuses profondes constituées. Etude comparative d’un fragment d’héparine de bas poids moléculaire (Fragminc) administré par voie sous-cutanée et de P héparine standard administrée par voie intraveineuse continue. Rev Méd Interne 1989; 10: 375-81
  • 9 A collaborative European Multicentre Study. A randomized 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: 251-6
  • 10 Prandoni P, Lensing AWA, Biiller HR, Carta M, Cogao A, Vigo M, Casara D, Ruol A, ten Cate JW. Comparison of subcutaneous low-molecularweight heparin with intravenous standard heparin in proximal deep-vein thrombosis. Lancet 1992; 339: 441-5
  • 11 Lopaciuk S, Meissner AJ, Filipecki S, Zawilska K, Sowier J, Ciesielski L, Bielawiec M, Glowinski S, Czestochowska E. et al 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
  • 12 Simonneau G, Charbonnier B, Décousus H, Planchon B, Ninet J, Sié 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: 1541-6
  • 13 Hull RD, Raskob GE, Pineo GF, Green D, Trowbridge AA, Elliot G, 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
  • 14 Marder VJ, Soulen RL, Atichartakarn 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: 1018-29
  • 15 Picolet H, Leizorovicz A, Revel D, Chirossel P, Amiel M, Boissel JP. Reliability of phlebography in the assessment of venous tluumbosis in a clinical trial. Haemostasis 1990; 20: 362-7
  • 16 Aiach M, Michaud A, Balian JL, Lefébvre M, Woler M, Fourtillan J. A new low molecular weight heparin derivative. In vitro and in vivo studies. Thromb Res 1983; 31: 611-21
  • 17 Béguin S, Wicldcrs S, Lormcau JC, Hemker HC. The mode of action of CY 216 and CY 23? in plasma. Thromb Haemost 1992; 67: 33-41
  • 18 Janvier G, Freyburger G, Winnonk S, Dugrnis G, Boisseau M, Boisscrias F. An open trial of enoxaparin in the treatment of deep vein thrombosis of the leg. Haemostasis 1991; 21: 161-8
  • 19 Levine MN, Planes A, Hirsh J, Goodyear M, Vochelle N, Gent M. The relationship between anti-factor Xa level and clinical outcome in patients receiving enoxaparin low molecular weight heparin to prevent deep vein thrombosis after hip replacement. Thromb Haemnsi 1989; 62: 940-4
  • 20 Bara L, Leizorovicz A, Picolct II, Samama M. Correlation between anti-Xa occurrence of thrombosis and haemorrhage in post-surgical patients treated with either Logiparm (LMWH) or unfractionatcd heparin. Thromb Res 1992; 65: 641-50
  • 21 Nieuwenhuis HK, Albada J, Banga JD, Sixma JJ. Identification of risk factors for bleeding during treatment of acute venous thromboembolism with heparin or low molecular weight heparin. Blood 1991; 78: 2337-43