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Warfarin resistance: diagnosis and therapeutic alternatives
1Department of Pharmacy Practice and Pharmacy Administration, Philadelphia College of Pharmacy and Science, PA 19104, USA.
Abstract:
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.
Insights
Warfarin resistance is uncommon, often due to external factors like drug interactions or noncompliance. Rare hereditary cases suggest genetic factors may cause abnormal vitamin K receptor or enzyme activity.
Area of Science:
- Pharmacology
- Genetics
- Internal Medicine
Background:
- Warfarin resistance is a rare clinical phenomenon, with limited literature primarily comprising case reports.
- Potential causes include noncompliance, excessive vitamin K intake, and drug interactions affecting warfarin efficacy.
- Hereditary warfarin resistance is exceptionally rare, with only a few documented cases.
Purpose of the Study:
- To review the literature on warfarin resistance.
- To explore potential mechanisms underlying warfarin resistance, particularly hereditary forms.
- To guide clinicians in diagnosing and managing warfarin resistance.
Main Methods:
- Literature review of MEDLINE database (1964-1995) focusing on warfarin resistance.
- Analysis of documented case reports, including hereditary cases.
- Discussion of potential etiological factors and diagnostic considerations.
Main Results:
- Most warfarin resistance cases are attributed to external factors.
- Three documented cases of hereditary warfarin resistance exist, with one additional loosely documented case.
- Hypothesized mechanism for hereditary resistance involves an abnormal vitamin K receptor or enzyme with increased affinity for vitamin K.
Conclusions:
- Clinicians must systematically exclude common causes of warfarin resistance before considering rarer etiologies.
- Hereditary warfarin resistance, though rare, may be linked to genetic variations affecting vitamin K metabolism or warfarin action.
- Further research is needed to identify the specific molecular basis of hereditary warfarin resistance.