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Evaluation of weight based enoxaparin dosing on anti-Xa concentrations in patients with obesity

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Abstract

Current treatment dose of enoxaparin is based on total body weight (TBW), however dosage in obesity remains unclear. “Dose capping” commonly occurs if TBW > 100 kg minimising bleeding risk. However, this may result in under-dosing and increasing embolisation risk. The primary objective evaluated efficacy of current dosing strategies in obese patients and determined if resultant anti-Xa concentrations (aXaC) were therapeutic. The secondary objective was to investigate if an uncapped 0.75–0.85 mg/kg (TBW) twice daily dose, advocated by previous authors, results in therapeutic aXaC (0.5–1.0 IU/ml). This retrospective study included 133 patients with a median TBW of 128 kg, producing 59% therapeutic, 15% sub-therapeutic and 26% supra-therapeutic aXaC. Approximately 60% of patients in each dose group (< 0.75, 0.75–0.85 and > 0.85 mg/kg) had a therapeutic aXaC, however the percentage of sub-therapeutic versus supra-therapeutic was higher in the < 0.75 (27% vs 9%) and > 0.85 mg/kg (10% vs 34%) groups respectively. Most patients who weighed 100–119 kg (TBW) received doses > 0.85 mg/kg, however 32% had toxic aXaC. Those between 120 and 139 kg (TBW) had a high percentage of therapeutic aXaC (87%) when dosed < 0.75 mg/kg and a high percentage of supra-therapeutic aXaC (71%) when dosed > 0.85 mg/kg; although numbers were low. Dose reduction occurred in patients > 140 kg (TBW), however < 0.75 mg/kg resulted in higher percentage of sub-therapeutic aXaC (42%). Dosing at 0.75–0.85 mg/kg results in 62% of therapeutic, 14% sub-therapeutic and 24% supra-therapeutic aXaC. This appears to be a “safe” starting dose-range, however all obese patients should have aXaC monitoring due to high inter-patient variability.

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References

  1. Antman ME, McCabe HC, Gurfinkel PE, Turpie GGA, Bernink JLMP, Salein BD, De Luna BA, Fox BK, Lablanche BJ-M, Radley BD, Premmereur BJ, Braunwald BE (1999) Enoxaparin prevents death and cardiac ischemic events in unstable angina/non-Q-wave myocardial infarction: results of the Thrombolysis In Myocardial Infarction (TIMI) 11B trial. Circulation 100(15):1593–1601. https://doi.org/10.1161/01.CIR.100.15.1593

    Article  CAS  PubMed  Google Scholar 

  2. Chao BH, Lepeak L, Leal T, Robins HI (2011) Clinical use of the low-molecular-weight heparins in cancer patients: focus on the improved patient outcomes. Thrombosis. https://doi.org/10.1155/2011/530183

    Article  PubMed  PubMed Central  Google Scholar 

  3. Green B, Duffull SB (2003) Development of a dosing strategy for enoxaparin in obese patients. Br J Clin Pharmacol 56(1):96–103

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Barras AM, Duffull BS, Atherton JJ, Green JB (2010) Individualized dosing of enoxaparin for subjects with renal impairment is superior to conventional dosing at achieving therapeutic concentrations. Ther Drug Monit 32(4):482–488. https://doi.org/10.1097/FTD.0b013e3181e64846

    Article  CAS  PubMed  Google Scholar 

  5. Hanley M, Abernethy D, Greenblatt D (2010) Effect of obesity on the pharmacokinetics of drugs in humans. Clin Pharmacokinet 49(2):71–87. https://doi.org/10.2165/11318100-000000000-00000

    Article  CAS  PubMed  Google Scholar 

  6. Lalama J, Feeney M, Vandiver J, Beavers K, Walter L, McClintic J (2015) Assessing an enoxaparin dosing protocol in morbidly obese patients. J Thromb Thrombolysis 39(4):516–521. https://doi.org/10.1007/s11239-014-1117-y

    Article  CAS  PubMed  Google Scholar 

  7. Lee YR, Vega JA, Duong HNQ, Ballew A (2015) Monitoring enoxaparin with antifactor Xa levels in obese patients. Pharmacother J Hum Pharmacol Drug Ther 35(11):1007–1015. https://doi.org/10.1002/phar.1658

    Article  CAS  Google Scholar 

  8. Patel JP, Roberts LN, Arya R (2011) Anticoagulating obese patients in the modern era. Br J Haematol 155:137–149. https://doi.org/10.1111/j.1365-2141.2011.08826.x

    Article  CAS  PubMed  Google Scholar 

  9. Deal EN, Hollands JM, Riney JN, Skrupky LP, Smith JR, Reichley RM (2011) Evaluation of therapeutic anticoagulation with enoxaparin and associated anti-Xa monitoring in patients with morbid obesity: a case series. J Thromb Thrombolysis 32(2):188–194. https://doi.org/10.1007/s11239-011-0584-7

    Article  PubMed  Google Scholar 

  10. Barras MA, Kirkpatrick CM, Green B (2010) Current dosing of low-molecular-weight heparins does not reflect licensed product labels: an international survey. Br J Clin Pharmacol 69(5):520–528. https://doi.org/10.1111/j.1365-2125.2010.03626.x

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Montalescot G, Collet JP, Tanguy ML (2004) Anti-Xa activity relates to survival and efficacy in unselected acute coronary syndrome patients treated with enoxaparin. ACC Curr J Rev 13(11):58–59. https://doi.org/10.1016/j.accreview.2004.10.060

    Article  Google Scholar 

  12. Sanofi-Aventis Australia Pty Ltd (1993) Clexane and Clexane Forte full product information. Monthly index of medical specialities online. https://www.mimsonline.com.au. Accessed July 2018

  13. Department of Health (2016) Guideline for anticoagulation and prophylaxis using low molecular weight heparin (LMWH) in adult inpatients. Queensland Government. https://www.health.qld.gov.au/__data/assets/pdf_file/0023/147533/qh-gdl-951.pdf

  14. Cohen M, Demers C, Gurfinkel EP, Turpie AGG, Fromell GJ, Goodman S, Langer A, Califf RM, Fox KAA, Premmereur J, Bigonzi F, Stephens J, Weatherley B (1997) A comparison of low-molecular-weight heparin with unfractionated heparin for unstable coronary artery disease. N Engl J Med 337(7):447–452. https://doi.org/10.1056/NEJM199708143370702

    Article  CAS  PubMed  Google Scholar 

  15. Merli GJ, Groce JB (2010) Pharmacological and clinical differences between low-molecular-weight heparins: implications for prescribing practice and therapeutic interchange. P&T Peer-Rev J Formul Manag 35(2):95

    Google Scholar 

  16. Sanderink GJ, Le Liboux A, Jariwala N, Harding N, Ozoux ML, Shukla U, Montay G, Boutouyrie B, Miro A (2002) The pharmacokinetics and pharmacodynamics of enoxaparin in obese volunteers. Clin Pharmacol Ther 72:308–318. https://doi.org/10.1067/mcp.2002.127114

    Article  CAS  PubMed  Google Scholar 

  17. Han PY, Duffull SB, Kirkpatrick CMJ, Green B (2007) Dosing in obesity: a simple solution to a big problem. Clin Pharmacol Ther 82(5):505. https://doi.org/10.1038/sj.clpt.6100381

    Article  CAS  PubMed  Google Scholar 

  18. Maclachlan KH, Stevens HP, Tran HA, Chunilal SD (2019) Weight-based enoxaparin for venous thromboembolism in obesity gives similar anti-xa levels to patients < 100 kg, with no increase in major bleeding. Semin Thromb Hemost 45(1):94–99. https://doi.org/10.1055/s-0038-1677019

    Article  CAS  PubMed  Google Scholar 

  19. Thompson-Moore N, Wanat MA, Putney D, Liebl P, Chandler W, Muntz J (2015) Evaluation and pharmacokinetics of treatment dose enoxaparin in hospitalized patients with morbid obesity. Clin Appl Thromb Hemost 21(6):513–520. https://doi.org/10.1177/1076029614568713

    Article  CAS  PubMed  Google Scholar 

  20. Nutescu E, Burnett A, Fanikos J, Spinler S, Wittkowsky A (2016) Pharmacology of anticoagulants used in the treatment of venous thromboembolism. J Thromb Thrombolysis 41(1):15–31

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Authors and Affiliations

  1. Princess Alexandra Hospital, Brisbane, Australia

    Nameer van Oosterom, Karl Winckel & Michael Barras

  2. The University of Queensland, Brisbane, Australia

    Nameer van Oosterom, Karl Winckel & Michael Barras

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  1. Nameer van Oosterom
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  2. Karl Winckel
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Correspondence to Nameer van Oosterom.

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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. This study was also approved by the Human Research Ethics Committee (Reference Number: HREC/16/QWMS/23).

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van Oosterom, N., Winckel, K. & Barras, M. Evaluation of weight based enoxaparin dosing on anti-Xa concentrations in patients with obesity. J Thromb Thrombolysis 48, 387–393 (2019). https://doi.org/10.1007/s11239-019-01847-4

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