Pharmacy World and Science

, Volume 22, Issue 4, pp 147–151 | Cite as

Stabilization of oral anticoagulant therapy in hospitalized patients and characteristics associated with lack of stabilization

  • P.M.L.A. van den Bemt
  • J.R.B.J. Brouwers
  • A. Risselada
  • M.H.A. van den Boogaart
  • A.C.G. Egberts


The initiation and stabilization of oral anticoagulant therapy in hospitalized patients in a setting without specialized medical or pharmaceutical advice, was studied. In addition, potential risk factors for lack of stabilization were studied. All patients from three wards (orthopaedic surgery, general surgery and internal medicine) in two Dutch hospitals, who were started on oral anticoagulant therapy and who gave informed consent, were included in this three months prospective follow‐up study. When a patient had two consecutive INR's within the range 2‐3 during hospitalization (on day 6 or later), he was defined as stable. Stable and unstable patients were compared with respect to age, gender, quetelet index, length of hospital stay, indication for oral anticoagulant therapy, induction dosing schedule of oral anticoagulant therapy, prescribing physician, type of hospital (teaching or non‐teaching), concurrently used drugs, concurrently used drugs known to potentially interact with oral anticoagulant therapy (drug‐drug interactions that influence INR) and (co)morbidity. A total of 125 patients, who all used acenocoumarol as oral anticoagulant, were recruited in the study. The study population mainly comprised orthopaedic discharges on prophylactic oral anticoagulants. The mean length of hospital stay was 14.5 days (median 11.0, standard deviation (SD) 10.2) for the patients included in the study (patients with a short length of stay < 6 days were excluded from the study, because of the definition of stability). 43 patients (34%) became stable during hospitalization. The second INR within the range was reached after on average 11.1 days (median 10.0, SD 4.5).18 different induction dosing schedules were used. Differences in apparent risk of INR instability were statistically associated with length of hospital stay (odds ratio (OR) 0.85, 95% confidence interal (CI) 0.78‐0.92), concurrent use of muscoloskeletal drugs, mainly NSAIDs, (OR 1.68, 95% CI 1.04‐2.72) and two individual prescribing physicians (OR 6.61, 95% CI 1.47‐29.82 for one physician and OR 0.23, 95% CI 0.06‐0.99 for the other physician). This population has a high percentage of instability and reaches stability relatively late. The instability was associated with length of hospital stay, the concurrent use of musculoskeletal drugs (mostly NSAID's) and physician. Most of the unstable patients had INR's below therapeutic range, suggesting a conservative dosing habit. Part of the instability may also be due to the many different physicians who dose their own patients. Interventions to improve dosing may aid in better stabilization in hospitalized patients and thus in reduced length of hospital stay.

Acenocoumarol Dosage INR Oral anticoagulant therapy Stabilization 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Haemostasis and Thrombosis Task Force for the British Committee for Standards in Haematology. Guidelines on oral anticoagulation: third edition. Br J Haematol 1998;101:374-87.Google Scholar
  2. 2.
    Fihn SD, McDonell M, Martin D, Henikoff J, Vermes D, Kent D, et al. for the Warfarin Optimized Outpatient Follow-up Study Group. Risk factors for complications of chronic anticoagulation. A multicenter study. Ann Intern Med 1993; 118:511-20.Google Scholar
  3. 3.
    Gulløv AL, Koefoed BG, Petersen P. Bleeding during warfarin and aspirin therapy in patients with atrial fibrillation. The AFASAK 2 study. Arch Intern Med 1999;159:1322-8.Google Scholar
  4. 4.
    Ansell JE. Anticoagulation management as a risk factor for adverse events: Grounds for improvement. J Thrombosis Thrombolysis 1998;5:S13-S18.Google Scholar
  5. 5.
    Anonymous. Anatomical Therapeutic Chemical (ATC) classification index. Oslo: WHO Collaborating Centre for Drug Statistics Methodology, 1994.Google Scholar
  6. 6.
    Fennerty A, Dolben J, Thomas P, Backhouse G, Bentley DP, Campbell IA, et al. Flexible induction dose regimen for warfarin and prediction of maintenance dose. BMJ 1984;288:1268-70.Google Scholar
  7. 7.
    Carter BL, Taylor JW, Becker A. Evaluation of three dosageprediction methods for initial in-hospital stabilization of warfarin therapy. Clin Pharm 1987;6:37-45.Google Scholar
  8. 8.
    White RH, Hong R, Venook AP, Daschbach MM, Murray W, Mungall DR, et al. Initiation of warfarin therapy: comparison of physician dosing with computer-assisted dosing. J Gen Intern Med 1987;2:141-8.Google Scholar
  9. 9.
    Vadher B, Patterson DLH, Leaning M. Evaluation of a decision support system for initiation and control of oral anticoagulation in a randomised trial. BMJ 1997;314:1252-6.Google Scholar
  10. 10.
    Kovacs MJ, Cruickshank M, Wells PS, Kim H, Chin-Yee I, Morrow B, et al. Randomized assessment of a warfarin nomogram for initial oral anticoagulation after venous thromboembolic disease. Haemostasis 1998;28:62-9.Google Scholar
  11. 11.
    Anonymus. Cumarinederivaten. In: Informatorium Medicamentorum 2000. 's Gravenhage: Koninklijke Nederlandse Maatschappij ter bevordering der Pharmacie, 2000:299.Google Scholar
  12. 12.
    Sun J, Chang MW. Initialization of warfarin dosages using computer modeling. Arch Phys Med Rehabil 1995;76:453-6.Google Scholar

Copyright information

© Kluwer Academic Publishers 2000

Authors and Affiliations

  • P.M.L.A. van den Bemt
    • 1
  • J.R.B.J. Brouwers
    • 2
  • A. Risselada
    • 3
  • M.H.A. van den Boogaart
    • 3
  • A.C.G. Egberts
    • 4
    • 5
  1. 1.Hospital Pharmacy Medisch Centrum Leeuwarden/De Tjongerschans HeerenveenGroningen University Institute for Drug Exploration (GUIDE) University Centre for PharmacyGroningenThe Netherlands
  2. 2.Hospital Pharmacy Medisch Centrum Leeuwarden/De Tjongerschans HeerenveenGroningen University Institute for Drug Exploration (GUIDE) University Centre for PharmacyGroningenThe Netherlands
  3. 3.Groningen University Institute for Drug Exploration (GUIDE), University Centre for PharmacyGroningenThe Netherlands
  4. 4.Hospital Pharmacy Midden-BrabantTilburgThe Netherlands
  5. 5.The Netherlands

Personalised recommendations