Optimal Initial Dose Adjustment of Warfarin in Orthopedic Patients

Warfarin sodium is commonly prescribed for the prophylaxis and treatment of venous thromboembolism. Dosing algorithms have not been widely adopted because they require a fixed initial warfarin dose (eg, 5 mg) and are not tailored to other factors that may affect the international normalized ratio (I...

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Bibliographic Details
Published in:The Annals of pharmacotherapy 2007-11, Vol.41 (11), p.1798-1804
Main Authors: Lenzini, Petra A, Grice, Gloria R, Milligan, Paul E, Gatchel, Susan K, Deych, Elena, Eby, Charles S, Burnett, R Stephen J, Clohisy, John C, Barrack, Robert L, Gage, Brian F
Format: Article
Language:English
Subjects:
Adolescent
Adult
Aged
Aged, 80 and over
Algorithms
Anticoagulants - administration & dosage
Anticoagulants - adverse effects
Anticoagulants - therapeutic use
Arthroplasty, Replacement, Hip
Arthroplasty, Replacement, Knee
Biological and medical sciences
Blood Loss, Surgical - prevention & control
Female
Humans
Hydroxymethylglutaryl-CoA Reductase Inhibitors - therapeutic use
International Normalized Ratio
Male
Medical sciences
Middle Aged
Pharmacology. Drug treatments
Prospective Studies
Pulmonary Embolism - prevention & control
Venous Thrombosis - prevention & control
Warfarin - administration & dosage
Warfarin - adverse effects
Warfarin - therapeutic use
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Summary:Warfarin sodium is commonly prescribed for the prophylaxis and treatment of venous thromboembolism. Dosing algorithms have not been widely adopted because they require a fixed initial warfarin dose (eg, 5 mg) and are not tailored to other factors that may affect the international normalized ratio (INR). To develop an algorithm that could predict a therapeutic warfarin dose based on drug interactions, INR response after the initial warfarin doses, and other clinical factors. We used stepwise regression to quantify the relationship between these factors in patients beginning prophylactic warfarin therapy immediately prior to joint replacement. In the derivation cohort (n = 271), we separately modeled the therapeutic dose after 2 and 3 initial doses. We prospectively validated these 2 models in an independent cohort (n = 105). About half of the therapeutic dose variability was predictable after 3 days of therapy: R2 was 53% in the derivation cohort and 42% in the validation cohort. INR response after 3 warfarin doses (INR3) inversely correlated with therapeutic dose (p < 0.001). Intraoperative blood loss transiently, but significantly, elevated the postoperative INR values. Other significant (p < 0.03) predictors were the first and second warfarin doses (+7% and +6%, respectively, per 1 mg), and statin use (-15.0%). The model derived after 2 warfarin doses explained 32% of the variability in therapeutic dose. We developed and validated algorithms that estimate therapeutic warfarin doses based on clinical factors and INR response available after 2-3 days of warfarin therapy. The algorithms are implemented online at www.WarfarinDosing.org.
ISSN:1060-0280
1542-6270
DOI:10.1345/aph.1K197