Warfarin resistance: diagnosis and therapeutic alternatives

Warfarin resistance is a rare phenomenon, and most of the related literature obtained in a MEDLINE search from 1964-1995 consists of case reports. Warfarin resistance may develop as a result of noncompliance, exogenous consumption of vitamin K, and concurrent ingestion of other agents known to decrease warfarin's effects. There are three documented cases of hereditary resistance and one case of loose documentation of hereditary resistance with confirmation of similar resistant patterns in family members. Data on two of the three cases may support the postulation that hereditary resistance may be caused by the presence of an abnormal receptor or enzyme that has an increased affinity for vitamin K. To date, this receptor or enzyme has not been identified. To assess a subtherapeutic dose response to oral anticoagulation, the clinician must consider many possible causes of resistance, such as noncompliance, drug interactions, laboratory error, or pharmacokinetic changes. Once these have been ruled out, it is possible to consider that a tissue resistance to warfarin may be responsible.