Pathophysiology of Haemostasis and Thrombosis

Original Paper

Free Access

Effect of Patient Weight on the Anticoagulant Response to Adjusted Therapeutic Dosage of Low-Molecular- Weight Heparin for the Treatment ofVenous Thromboembolism

Wilson S.J-A.a · Wilbur K.d · Burton E.b · Anderson D.R.c

Author affiliations

aFaculty of Health Professions, Dalhousie University, and Pharmacy Department, bData Base Department and cDepartment of Medicine, Division of Hematology, Queen Elizabeth II Health Sciences Centre, Halifax, N.S., and dFaculty of Pharmaceutical Sciences, University of British Columbia and Vancouver Hospital and Health Sciences Centre, Vancouver, B.C., Canada

Corresponding Author

Dr. S. Jo-Anne Wilson, Queen Elizabeth II Health Sciences Centre

Pharmacy Department – Victoria General, Room 2043 Victoria

Halifax, NS B3H 2Y9 (Canada)

Tel. +1 902 473 6600, Fax +1 902 473 6812

E-Mail RXJSW@qe2-hsc.ns.ca

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Haemostasis 2001;31:42–48

Abstract

Data evaluating the safety of using weight-based dosing of low-molecular-weight heparin (LMWH) in obese patients are limited. Some manufacturers have recommended a maximum daily dose of LMWH not to be exceeded. The purpose of this study was to determine if body weight influenced the anticoagulant response to a weight-based dose of LMWH for the treatment of venous thromboembolism. Patients with serum creatinine levels <150 µmol/l receiving the LMWH , dalteparin 200 anti-Xa IU/kg based on actual body weight subcutaneously once daily for the treatment of deep vein thrombosis or pulmonary embolism, were eligible for the study. Patients received a minimum of 5 days LMWH treatment. Patients had peak anti-Xa levels (IL Test Chromogenic assay) measured 3–4 h following their day 3 injection and trough anti-Xa levels measured immediately prior to injections on day 3 and 5. No dose adjustments were made on the basis of the anti-Xa levels. Patients were a priori stratified into three weight classes: (A) within 20% of ideal body weight (IBW) (n = 13); (B) 20–40% of IBW (n = 14), and (C) greater than 40% of IBW (n = 10). The largest patient weighed 190 kg and had a body mass index of 58. Mean daily LMWH doses were 14,030, 17,646 and 23, 565 IU for groups A, B and C, respectively. Mean (SD) trough anti-Xa levels on day 3 were 0.12 (0.05) anti-Xa IU/ml for group A, 0.11 (0.03) anti-Xa IU/ml for group B and 0.11 (0.03) anti-Xa IU/ml for group C (p > 0.2). Similar trough anti-Xa levels were observed on day 5. Mean (SD) peak anti-Xa levels on day 3 were 1.01 (0.20) anti-Xa IU/ml, 0.97 (0.21) anti-Xa IU/ml and 1.12 (0.22) anti-Xa IU/ml for groups A, B and C, respectively (p > 0.2). No thromboembolic or bleeding complications occurred during LMWH therapy in any patients. These findings suggest that body mass does not appear to have an important effect on the response to LMWH up to a weight of 190 kg in patients with normal or near normal renal function.

© 2001 S. Karger AG, Basel




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References

  1. 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, Grant 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.
  2. Simmonneau G, Sors H, Charbonnoi B, Decousus H, Planchon B, Ninet J, Sie P, Silsiguen M, Combe S: Subcutaneous low-molecular-weight heparin compared with continuous intravenous infusion unfractionated heparin in the treatment of proximal deep vein thrombosis. Arch Intern Med 1993;153:1541–1546.
  3. Lindmarker P, Holmstrom 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.
    External Resources
  4. Luomanmaki K, Grankvist S, Hallert C, Jauro I, Ketola K, Kim HC, Kiviniemi H, Koskivirta H, Sorskog L, Vilkko P: A multicentre comparison of once-daily subcutaneous dalteparin (low-molecular-weight heparin) and continuous intravenous heparin in the treatment of deep vein thrombosis. J Intern Med 1996;240:85–92.
    External Resources
  5. Levine M, Gent M, Hirsh J, Leclerc J, Anderson DR, Weitz J, Ginsberg J, Turpie AG, Demers C, Kovacs M: A comparison of low-molecular-weight heparin administered primary at home with unfractionated heparin administered in the hospital for proximal deep vein thrombosis. N Engl J Med 1996;334:677–681.
  6. Koopman M, Prandoni L, Piovella F, Ockelford PA, Brandjes DP, Van der Meer J, Gallas AS, Simonneau G, Chesterman CA, Prins MH: Treatment of venous thromboembolism with intravenous unfractionated heparin administered in the hospital as compared with subcutaneous low-molecular-weight heparin administered at home. N Engl J Med 1996;334:682–687.
  7. The Columbus Investigators: Low-molecular-weight heparin in the treatment of patients with venous thromboembolism. N Engl J Med 1997;337:657–662.
  8. Hull RD, Raskob GE, Rosenbloom D, Pineo GF, Lerner RG, Fafni A, Trowbridge AA, Elliott CG, Green D, Feinglass J: Treatment of proximal vein thrombosis with subcutaneous low-molecular-weight heparin versus intravenous heparin: An economic perspective. Arch Intern Med 1993;157:259–294.
    External Resources
  9. Fragmin product monograph. Mississauga/Ont., Pharmacia Inc, 2000.
  10. Weitz JI: Low-molecular-weight heparins. N Engl J Med 1997;337:688–698.
  11. Kovacs MJ, Cruickshank M, Wells PS, Kim H, Chin-Yee I, Morrow B, Boyle E, Kovacs J: Randomized assessment of a warfarin nomogram for initial oral anticoagulation after venous thromboembolism disease. Haemostasis 1998;28:62–69.
  12. Devine BJ: Gentimicin therapy. Drug Intell Clin Ther 1974;8:650–655.
  13. Anderson DR, Levine M, Gent M: Validation of a new criteria for the evaluation of bleeding during antithrombotic therapy. Thromb Haemost 1993;69:650.
  14. Boneau B: Low-molecular-weight heparin therapy: Is monitoring needed? Thromb Haemost 1994;72:330–334.
  15. Alhenc-Gelas M, Guernic JL, Vitoux JF, Kher A, Ajach M, Fiessinger JN: Adjusted versus fixed doses of the low-molecular-weight heparin Fragmin in the treatment of deep vein thrombosis. Thromb Haemost 1994;71:698–702.
    External Resources
  16. Kovacs MJ, Wier K, MacKinnon K, Keeney M, Brien WF, Cruickshank M: Body weight does not predict for anti-Xa levels after fixed dose prophylaxis with enoxaparin after orthopedic surgery. Thromb Res 1998;91:129–136.
  17. Kakkar VV, Kadziola Z, Mertes R: Does efficacy and safety of LMWH prophylaxis after total hip replacement depend upon body weight. Thromb Haemost 1999;61:abstr 183.
  18. Samama MM, Verhille C, Darchy L: Relation between weight, obesity and frequency of deep venous thrombosis after enoxaparin in orthopedic surgery. Thromb Haemost 1995;977:abstr 300.
  19. Bara L, Leizorovicz A, Picolet H, Samama M: Correlation between anti-Xa and occurrence of thrombosis and haemorrhage in post-surgical patients treated with either Logiparin® (LMWH) or unfractionated heparin. Thromb Res 1992;65:641–650.
    External Resources
  20. Vitoux JF, Aiach M, Roncato M, Fiessinger JN: Should thromboprophylactic dosage of low-molecular-weight heparin be adapted to patient weight? Thromb Haemost 1988;59:120.
    External Resources
  21. Bacher P, Horst B, Breyer HG, Hoppensteadt DA, Walenga JM, Fareed J: Postoperative monitoring of low-molecular-weight heparin prophylaxis in high-risk patients. Semin Thromb Hemost 1993;19:73–78.
  22. Leizorovicz A, Bara L, Samama MM, Haugh MC: Factor Xa inhibition: Correlation between the plasma levels of anti-Xa activity and occurrence of thrombosis and haemorrhage. Haemostasis 1993;23:89–98.
    External Resources
  23. Leyvraz PF, Bachmann F, Hoek J, Buller HR, Postel M, Samama M, Vandenbrock MD: Prevention of deep vein thrombosis after hip replacement: Randomized comparison between unfractionated heparin and low-molecular-weight heparin. BMJ 1991;303:543–548.
  24. Levine MN, Planes A, Hirsh J, Goodyear M, Vochelle N, Gent M: The relationship between anti-factor Xa level and clinical outcomes in patients receiving enoxaparin low-molecular-weight heparin to prevent deep vein thrombosis after hip replacement. Thromb Haemost 1989;62:940–944.
  25. 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;78:2337–2343.
  26. Bara L, Planes A, Samama MM: Occurrence of thrombosis and haemorrhage, relationship with anti-Xa, anti-IIa activities and D-dimer plasma levels in patients receiving a low-molecular-weight heparin, enoxaparin or tinzaparin, to prevent deep vein thrombosis after hip surgery. Br J Haematol 1999;104:230–240.

Article / Publication Details

First-Page Preview
Abstract of Original Paper

Published online: June 15, 2001
Issue release date: June 2001

Number of Print Pages: 7
Number of Figures: 0
Number of Tables: 2

ISSN: 1424-8832 (Print)
eISSN: 1424-8840 (Online)

For additional information: https://www.karger.com/PHT


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