Warfarin resistance refers to the need for high doses of warfarin (20 mg or more per day) to achieve a therapeutic increase in the prothrombin time (PT) and INR.

Causes associated with low serum warfarin levels:

(1) noncompliance

(2) malabsorption of warfarin from the GI tract or diarrhea

(3) drug-induced increase in warfarin metabolism

(4) enhanced metabolism or clearance due to a non-drug mechanism


Causes associated with a high serum warfarin level:

(1) hereditary resistance, due to an abnormal vitamin K epoxide reductase (resistance shared by other family members)

(2) high vitamin K intake

(2a) from diet

(2b) from parenteral nutrition

(2c) from herbal remedy (Eruca sativa, other)

(3) laboratory error in performance of the PT or calculation of the INR


The hazard of an acquired resistance due to drug therapy or source of vitamin K is that the patient will become overcoagulated if:

(1) the cause of the resistance stops AND

(2) the dose of warfarin is not reduced.

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