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.