Skip to main content
SpringerLink
Log in

Anti-Xa Levels 4 h After Subcutaneous Administration of 5,700 IU Nadroparin Strongly Correlate with Lean Body Weight in Morbidly Obese Patients

  • Clinical Research
  • Published:
Obesity Surgery Aims and scope Submit manuscript

Abstract

Background

Morbidly obese patients (BMI > 40 kg/m2) are at increased risk for venous thromboembolism, especially after surgery. Despite limited evidence, morbidly obese patients are often administered a double dose of nadroparin for thromboprophylaxis compared to non-obese patients. The aim of this study was to evaluate the influence of different body size descriptors on anti-Xa levels after a double dose of nadroparin (5,700 IU) in morbidly obese patients.

Methods

In 27 morbidly obese patients with a mean total body weight of 148 kg (range 107–260 kg), anti-Xa levels were determined peri-operatively until 24 h after administration of a subcutaneous dose of 5,700 IU of nadroparin.

Results

Anti-Xa level 4 h after administration (A4h, mean 0.22 ± 0.07 IU/ml) negatively correlated strongly with lean body weight (r = −0.66 (p < 0.001)) and moderately with total body weight (r = −0.56 (p = 0.003)) and did not correlate with body mass index (r = −0.26 (p = 0.187)). The area under the anti-Xa level-time curve from 0 to 24 h (AUA0–24h, mean 2.80 ± 0.97 h IU/ml) correlated with lean body weight (r = −0.63 (p = 0.007)), but did not correlate with total body weight (r = −0.44 (p = 0.075)) or body mass index (r = −0.10 (p = 0.709)).

Conclucions

Following a subcutaneous dose of nadroparin 5,700 IU, A4h and AUA0–24h were found to negatively correlate strongly with lean body weight. From these results, individualized dosing of nadroparin based on lean body weight should be considered in morbidly obese patients.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Ogden CL, Carroll MD, Curtin LR, et al. Prevalence of overweight and obesity in the United States, 1999-2004. JAMA. 2006;295(13):1549–55.

    Article  PubMed  CAS  Google Scholar 

  2. Stein PD, Beemath A, Olson RE. Obesity as a risk factor in venous thromboembolism. Am J Med. 2005;118(9):978–80.

    Article  PubMed  Google Scholar 

  3. Turpie AG, Chin BS, Lip GY. Venous thromboembolism: pathophysiology, clinical features, and prevention. BMJ. 2002;325(7369):887–90.

    Article  PubMed  Google Scholar 

  4. Duplaga BA, Rivers CW, Nutescu E. Dosing and monitoring of low-molecular-weight heparins in special populations. Pharmacotherapy. 2001;21(2):218–34.

    Article  PubMed  CAS  Google Scholar 

  5. Geerts WH, Bergqvist D, Pineo GF, et al. Prevention of venous thromboembolism: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). Chest. 2008;133(6 Suppl):381S–453S.

    Article  PubMed  CAS  Google Scholar 

  6. Hirsh J, Raschke R. Heparin and low-molecular-weight heparin: the Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy. Chest. 2004;126(3 Suppl):188S–203S.

    Article  PubMed  CAS  Google Scholar 

  7. Nutescu EA, Spinler SA, Wittkowsky A, et al. Low-molecular-weight heparins in renal impairment and obesity: available evidence and clinical practice recommendations across medical and surgical settings. Ann Pharmacother. 2009;43(6):1064–83.

    Article  PubMed  CAS  Google Scholar 

  8. Rondina MT, Wheeler M, Rodgers GM, et al. Weight-based dosing of enoxaparin for VTE prophylaxis in morbidly obese, medically-ill patients. Thromb Res. 2010;125(3):220–3.

    Article  PubMed  CAS  Google Scholar 

  9. Borkgren-Okonek MJ, Hart RW, Pantano JE, et al. Enoxaparin thromboprophylaxis in gastric bypass patients: extended duration, dose stratification, and antifactor Xa activity. Surg Obes Relat Dis. 2008;4(5):625–31.

    Article  PubMed  Google Scholar 

  10. Singh K, Podolsky ER, Um S, et al. Evaluating the safety and efficacy of BMI-based preoperative administration of low-molecular-weight heparin in morbidly obese patients undergoing Roux-en-Y gastric bypass surgery. Obes Surg. 2011 Apr 9. doi:10.1007/s11695-011-0397-y.

  11. Kalfarentzos F, Stavropoulou F, Yarmenitis S, et al. Prophylaxis of venous thromboembolism using two different doses of low-molecular-weight heparin (nadroparin) in bariatric surgery: a prospective randomized trial. Obes Surg. 2001;11(6):670–6.

    Article  PubMed  CAS  Google Scholar 

  12. Janmahasatian S, Duffull SB, Ash S, et al. Quantification of lean bodyweight. Clin Pharmacokinet. 2005;44(10):1051–65.

    Article  PubMed  Google Scholar 

  13. Rowland M, Tozer T. Clinical pharmacokinetics and pharmacodynamics: concepts and applications. 4th ed. Philadelphia: Lippincott Williams and Wilkins; 2010.

    Google Scholar 

  14. Agnelli G, Iorio A, Renga C, et al. Prolonged antithrombin activity of low-molecular-weight heparins. Clinical implications for the treatment of thromboembolic diseases. Circulation. 1995;92(10):2819–24.

    PubMed  CAS  Google Scholar 

  15. Boneu B, Navarro C, Cambus JP, et al. Pharmacodynamics and tolerance of two nadroparin formulations (10,250 and 20,500 anti Xa IU x ml(-1)) delivered for 10 days at therapeutic dose. Thromb Haemost. 1998;79(2):338–41.

    PubMed  CAS  Google Scholar 

  16. Collignon F, Frydman A, Caplain H, et al. Comparison of the pharmacokinetic profiles of three low molecular mass heparins—dalteparin, enoxaparin and nadroparin—administered subcutaneously in healthy volunteers (doses for prevention of thromboembolism). Thromb Haemost. 1995;73(4):630–40.

    PubMed  CAS  Google Scholar 

  17. Freedman MD, Leese P, Prasad R, et al. An evaluation of the biological response to fraxiparine, (a low molecular weight heparin) in the healthy individual. J Clin Pharmacol. 1990;30(8):720–7.

    PubMed  CAS  Google Scholar 

  18. Harenberg J, Wurzner B, Zimmermann R, et al. Bioavailability and antagonization of the low molecular weight heparin CY 216 in man. Thromb Res. 1986;44(4):549–54.

    Article  PubMed  CAS  Google Scholar 

  19. Heizmann M, Baerlocher GM, Steinmann F, et al. Anti-Xa activity in obese patients after double standard dose of nadroparin for prophylaxis. Thromb Res. 2002;106(4–5):179–81.

    Article  PubMed  CAS  Google Scholar 

  20. Harenberg J. Is laboratory monitoring of low-molecular-weight heparin therapy necessary? Yes. J Thromb Haemost. 2004;2(4):547–50.

    Article  PubMed  CAS  Google Scholar 

  21. Paige JT, Gouda BP, Gaitor-Stampley V, et al. No correlation between anti-factor Xa levels, low-molecular-weight heparin, and bleeding after gastric bypass. Surg Obes Relat Dis. 2007;3(4):469–75.

    Article  PubMed  Google Scholar 

  22. Bounameaux H, de Moerloose P. Is laboratory monitoring of low-molecular-weight heparin therapy necessary? No. J Thromb Haemost. 2004;2(4):551–4.

    Article  PubMed  CAS  Google Scholar 

  23. Barras MA, Duffull SB, Atherton JJ, et al. Individualized compared with conventional dosing of enoxaparin. Clin Pharmacol Ther. 2008;83(6):882–8.

    Article  PubMed  CAS  Google Scholar 

  24. Lemmens HJ, Bernstein DP, Brodsky JB. Estimating blood volume in obese and morbidly obese patients. Obes Surg. 2006;16(6):773–6.

    Article  PubMed  Google Scholar 

  25. Frydman A. Low-molecular-weight heparins: an overview of their pharmacodynamics, pharmacokinetics and metabolism in humans. Haemostasis. 1996;26 Suppl 2:24–38.

    PubMed  CAS  Google Scholar 

  26. Sanderink GJ, Le Liboux A, Jariwala N, et al. The pharmacokinetics and pharmacodynamics of enoxaparin in obese volunteers. Clin Pharmacol Ther. 2002;72(3):308–18.

    Article  PubMed  CAS  Google Scholar 

  27. Ribstein J, du Cailar G, Mimran A. Combined renal effects of overweight and hypertension. Hypertension. 1995;26(4):610–5.

    PubMed  CAS  Google Scholar 

Download references

Acknowledgements

The authors would like to thank Brigitte Bliemer and Silvia Samson for their enthusiastic support and participation in this study. Esther Janssen is acknowledged for her contribution to this study and Saskia de Mik-van Ham for the editorial assistance.

Conflict of interest

There is no conflict of interest for all authors: Jeroen Diepstraten, Christian M. Hackeng, Simone van Kralingen, Jiri Zapletal, Eric P.A. van Dongen, René J. Wiezer, Bert van Ramshorst, Catherijne A.J. Knibbe

Author information

Authors and Affiliations

  1. Department of Clinical Pharmacy, St. Antonius Hospital, Koekoekslaan 1, 3435, CM, Nieuwegein, Netherlands

    Jeroen Diepstraten & Catherijne A. J. Knibbe

  2. Department of Clinical Chemistry, St. Antonius Hospital, Koekoekslaan 1, 3435, CM, Nieuwegein, Netherlands

    Christian M. Hackeng

  3. Department of Anesthesiology and Intensive Care, St. Antonius Hospital, Koekoekslaan 1, 3435, CM, Nieuwegein, Netherlands

    Simone van Kralingen & Eric P. A. van Dongen

  4. Department of Anesthesiology, St. Lucas Andreas Hospital, Jan Tooropstraat 164, 1061, AE, Amsterdam, Netherlands

    Simone van Kralingen

  5. Department of Radiology, St. Antonius Hospital, Koekoekslaan 1, 3435, CM, Nieuwegein, Netherlands

    Jiri Zapletal

  6. Department of Surgery, St. Antonius Hospital, Koekoekslaan 1, 3435, CM, Nieuwegein, Netherlands

    René J. Wiezer & Bert van Ramshorst

  7. Division of Pharmacology, Leiden/Amsterdam Center for Drug Research, Leiden, Netherlands

    Catherijne A. J. Knibbe

Authors
  1. Jeroen Diepstraten
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Christian M. Hackeng
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Simone van Kralingen
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Jiri Zapletal
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Eric P. A. van Dongen
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. René J. Wiezer
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Bert van Ramshorst
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Catherijne A. J. Knibbe
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Catherijne A. J. Knibbe.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Diepstraten, J., Hackeng, C.M., van Kralingen, S. et al. Anti-Xa Levels 4 h After Subcutaneous Administration of 5,700 IU Nadroparin Strongly Correlate with Lean Body Weight in Morbidly Obese Patients. OBES SURG 22, 791–796 (2012). https://doi.org/10.1007/s11695-012-0602-7

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11695-012-0602-7

Keywords

Search

Navigation