Optimal initial dose adjustment of warfarin in orthopedic patients.
BACKGROUND
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).


OBJECTIVE
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.


METHODS
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).


RESULTS
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.


CONCLUSIONS
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.
Lenzini
Petra A
PA
Washington University in St. Louis, St. Louis, MO 63110, USA.
Grice
Gloria R
GR
Milligan
Paul E
PE
Gatchel
Susan K
SK
Deych
Elena
E
Eby
Charles S
CS
Burnett
R Stephen J
RS
Clohisy
John C
JC
Barrack
Robert L
RL
Gage
Brian F
BF
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000465:Algorithms; D000925:Anticoagulants / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D019644:Arthroplasty, Replacement, Hip; D019645:Arthroplasty, Replacement, Knee; D016063:Blood Loss, Surgical / Q000517:prevention & control; D005260:Female; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use; D019934:International Normalized Ratio; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D011655:Pulmonary Embolism / Q000517:prevention & control; D020246:Venous Thrombosis / Q000517:prevention & control; D014859:Warfarin / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use
D000925:Anticoagulants; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D014859:Warfarin