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[Partial resistance to acenocoumarol and phenprocoumon caused by enzyme polymorphism]
E B Wilms1, R F Veldkamp, E van Meegen
1Apotheek Haagse Ziekenhuizen, Den Haag. e.wilms@ahz.nl
Nederlands Tijdschrift Voor Geneeskunde
|October 14, 2006
Summary
This study details a patient with partial resistance to coumarin anticoagulants due to a vitamin K epoxide reductase gene polymorphism. High-dose phenprocoumon successfully achieved therapeutic anticoagulation, highlighting a rare but manageable condition.
Area of Science:
- Pharmacogenomics
- Cardiology
- Internal Medicine
Background:
- Coumarin derivatives are standard anticoagulants for conditions like myocardial infarction.
- Standard dosing of acenocoumarol and phenprocoumon failed to achieve therapeutic anticoagulation in this patient.
- Investigating resistance mechanisms is crucial for effective anticoagulant therapy.
Observation:
- The patient required exceptionally high doses of phenprocoumon (18-21 mg daily) for anticoagulation.
- Phenprocoumon serum concentrations were ten times higher than normal, with low vitamin K1 levels.
- Other causes for treatment resistance were systematically excluded.
Findings:
- Partial resistance to coumarin derivatives was diagnosed, linked to a vitamin K epoxide reductase (VKORC1) gene polymorphism.
- This genetic variation necessitates significantly higher anticoagulant doses (10-20 times standard).
- Phenprocoumon was effective and convenient due to lower tablet count compared to acenocoumarol.
Implications:
- Congenital VKORC1 polymorphism is a rare cause of significant coumarin resistance.
- Monitoring drug serum concentrations aids in diagnosing treatment resistance.
- Personalized dosing strategies are essential for patients with genetic variations affecting drug metabolism.
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