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Journal of Thrombosis and Thrombolysis

, Volume 36, Issue 1, pp 96–101 | Cite as

Comparison of initial warfarin response in obese patients versus non-obese patients

  • Jessica L. Wallace
  • Anne B. Reaves
  • Elizabeth A. Tolley
  • Carrie S. Oliphant
  • Lydia Hutchison
  • Numan Abdulraman Alabdan
  • Christopher W. Sands
  • Timothy H. SelfEmail author
Article

Abstract

Achieving therapeutic anticoagulation with warfarin is complicated by substantial inter-patient and intra-patient variability with numerous factors known to influence dose requirements. Obesity is one factor for which there remains no study to date investigating its initial effect on warfarin response assessed by INR, stratified by BMI category in hospitalized patients. To compare initial warfarin response between obese and non-obese patients by evaluating average daily dose (ADD), time required to attain therapeutic INR, and mean discharge dose (MDD), stratified by BMI category. A retrospective review was conducted to evaluate initial warfarin response in hospitalized patients of different BMI categories initiated on warfarin with ≥4 consecutive days of therapy and managed by pharmacy dosing service. 211 patients were included (10 underweight, 45 normal weight, 48 overweight, 71 obese, 37 morbidly obese). Across BMI categories, the percentage of patients attaining therapeutic INR prior to discharge differed (p = 0.0004) with 71.1 % of normal weight therapeutic compared to 42.3 % of obese and 38 % of morbidly obese. Within BMI categories, when comparing ADD between patients therapeutic and subtherapeutic at discharge, no differences were observed, except among overweight patients (5.6 ± 0.3 vs. 7 ± 0.4 mg, p = 0.0143). Compared to normal weight, obese and morbidly obese required a significantly longer median time to achieve therapeutic INR (8 and 10 days vs. 6 days) and a higher ADD (6.6 ± 0.3 and 7.6 ± 0.5 vs. 5 ± 0.3 mg) and MDD (6.7 ± 0.5 and 6.7 ± 0.7 vs. 4.4 ± 0.5 mg). Compared to normal weight, obese and morbidly obese patients had a decreased initial response to warfarin.

Keywords

Warfarin Obesity Initial dosing 

Notes

Acknowledgments

Financial support for this project was provided in part by the University of Tennessee Health Science Center and Methodist University Hospital.

Conflict of interest

The authors declare that they have no conflict of interest.

References

  1. 1.
    Oake N, Fergusson DA, Forster AJ, van Walraven C (2007) Frequency of adverse events in patients with poor anticoagulation: a meta-analysis. CMAJ 176:1589–1594PubMedGoogle Scholar
  2. 2.
    Holbrook A, Schulman S, Witt DM et al (2012) Evidence-based management of anticoagulant therapy: antithrombotic therapy and prevention of thrombosis, 9th ed: American College of Chest Physicians evidence-based clinical practice guidelines. Chest 141:152S–184SCrossRefGoogle Scholar
  3. 3.
    Garcia D, Regan S, Crowther M, Hughes RA, Hylek EM (2005) Warfarin maintenance dosing patterns in clinical practice: implications for safer anticoagulation in the elderly population. Chest 127:2049–2056PubMedCrossRefGoogle Scholar
  4. 4.
    Aithal GP, Day CP, Kesteven PJ, Daly AK (1999) Association of polymorphisms in cytochrome P450 CYP2C9 with warfarin dose requirement and risk of bleeding complications. Lancet 353:717–719PubMedCrossRefGoogle Scholar
  5. 5.
    Schwarz UI, Ritchie D, Bradford Y, Li C, Dudek SM, Frye-Anderson A, Kim RB, Roden DM, Stein CM (2008) Genetic determinants of response to warfarin during initial anticoagulation. N Engl J Med 358:999–1008PubMedCrossRefGoogle Scholar
  6. 6.
    Gage BF, Eby C, Milligan PE, Banet GA, Duncan JR, McLeod HL (2004) Use of pharmacogenetics and clinical factors to predict the maintenance dose of warfarin. Thromb Haemost 91:87–94PubMedGoogle Scholar
  7. 7.
    Eichenger S, Hron G, Bialonczyk C et al (2008) Overweight, obesity and the risk of recurrent venous thromboembolism. Arch Intern Med 168(15):1678–1683CrossRefGoogle Scholar
  8. 8.
    Zu Schwabedissen CM, Schmitz VMF, Woodruff S et al (2006) Obesity is associated with a slower response to initial phenprocoumon therapy whereas CYP2C9 genotypes are not. Eur J Clin Pharmacol 62:713–720CrossRefGoogle Scholar
  9. 9.
    National Institutes of Health (1998) Clinical guidelines on the identification, evaluation, and treatment of overweight and obesity in adults: the evidence report. Obes Res 6(Suppl 2):51S–209SGoogle Scholar
  10. 10.
    Eccles JT (1975) Control of warfarin therapy in the elderly. Age Ageing 4:161–165PubMedCrossRefGoogle Scholar
  11. 11.
    Routledge PA, Chapman PH, Davies DM, Rawlins MD (1979) Factors affecting warfarin requirements. Eur J Clin Pharmacol 15:319–322PubMedCrossRefGoogle Scholar
  12. 12.
    Kamali F, Khan TI, King BP et al (2004) Contribution of age, body size, and CYP2C9 genotype to anticoagulant response to warfarin. Clin Pharmacol Ther 75:204–212PubMedCrossRefGoogle Scholar
  13. 13.
    Ageno W, Steid L, Ultori C et al (2003) The initial phase of oral anticoagulation with warfarin in outpatients with deep venous thrombosis. Blood Coagul Fibrinolysis 14:11–14PubMedCrossRefGoogle Scholar
  14. 14.
    Gage BF, Eby C, Johnson JA et al (2008) Use of pharmacogenetic and clinical factors to predict the therapeutic dose of warfarin. Clin Pharmacol Ther 84:326–331PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2012

Authors and Affiliations

  • Jessica L. Wallace
    • 1
    • 4
    • 5
  • Anne B. Reaves
    • 5
    • 6
  • Elizabeth A. Tolley
    • 2
  • Carrie S. Oliphant
    • 5
    • 6
  • Lydia Hutchison
    • 5
    • 6
  • Numan Abdulraman Alabdan
    • 3
  • Christopher W. Sands
    • 7
    • 8
  • Timothy H. Self
    • 1
    • 5
    Email author
  1. 1.Department of Clinical PharmacyUniversity of Tennessee Health Science Center (UTHSC)MemphisUSA
  2. 2.Department of Preventive MedicineUniversity of Tennessee Health Science Center (UTHSC)MemphisUSA
  3. 3.College of PharmacyUniversity of Tennessee Health Science Center (UTHSC)MemphisUSA
  4. 4.Department of Pharmacy PracticeCollege of Pharmacy, Lipscomb UniversityNashvilleUSA
  5. 5.Department of PharmacyMethodist University HospitalMemphisUSA
  6. 6.Department of Clinical PharmacyUniversity of Tennessee Health Science Center (UTHSC)MemphisUSA
  7. 7.Department of MedicineUniversity of Tennessee Health Science Center (UTHSC)MemphisUSA
  8. 8.Methodist Inpatient PhysiciansMethodist University HospitalMemphisUSA

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