Frequency and causes of overanticoagulation and underanticoagulation in patients treated with warfarin.

STUDY
OBJECTIVE: To determine the frequency and the specific causes of over- and underanticoagulation in patients who receive warfarin therapy and are managed in an anticoagulation clinic.
DESIGN: Retrospective medical record review.
SETTING: University-affiliated anticoagulation clinic.
SUBJECTS: One thousand twenty patients (mean age 60.2 yrs [range 17-84 yrs]) receiving warfarin therapy during a 1-year index period.
MEASUREMENTS AND MAIN RESULTS: Of 12,897 international normalized ratios (INRs) evaluated, 6642 (51.5%) were within range and 8525 (66.1%) were within 0.2 INR units of range. Among 2881 out-of-range INRs below 2.0, the most common cause of underanticoagulation was indeterminate (856, 29.7%). Response to previous change in dosage (16.4%), noncompliance or dosing errors (16.3%), and initiation of therapy (15.6%) were other common causes of underanticoagulation. Changes in drugs, medical condition, dietary vitamin K intake, alcohol use, and activity level, in combination, accounted for only 15.1% of INRs below 2.0. Among 603 out-of-range INRs greater than 4.0, the most common cause of overanticoagulation was indeterminate (43.0%). Changes in medical condition (15.9%), response to a previous change in warfarin dosage (11.4%), and interactions with prescription drugs (7.3%) were other common causes of overanticoagulation. In combination, noncompliance or dosing errors, initiation of therapy, and change in dietary vitamin K intake accounted for only 15.4% of INR values above 4.0.
CONCLUSION: Out-of-range INRs are encountered frequently during warfarin therapy as a result of changes in numerous factors. Despite extensive evaluation of potential causes of over- and underanticoagulation, a specific cause commonly cannot be determined.