title: [Partial resistance to acenocoumarol and phenprocoumon caused by enzyme polymorphism].
abstract: A 78-year-old man was treated with coumarin derivatives following myocardial infarction. The international normalised ratio was not increased by using standard loading doses and dose adjustments for acenocoumarol and phenprocoumon. The desired level of anticoagulation was achieved with a high dosage of phenprocoumon (18-21 mg daily). This dose was associated with a phenprocoumon serum concentration that was ten times higher than the normal therapeutic concentration. The serum concentration of vitamin K1 was low. After exclusion of alternative causes, we concluded that the exceptionally high dose of phenprocoumon needed was due to partial resistance to coumarin derivatives. Partial resistance is related to a polymorphism of the gene coding for the enzyme vitamin K epoxide reductase. The patient was successfully treated with chronic high-dose phenprocoumon. Resistance to coumarin derivatives caused by a congenital polymorphism in the vitamin K reductase gene is a rare phenomenon. Resistance is seldom absolute. The desired anticoagulation effect can be achieved with doses that are 10-20 times higher than standard doses. Phenprocoumon is advantageous in this situation because it requires fewer tablets than acenocoumarol. Determination of serum concentrations of acenocoumarol and phenprocoumon can be used to exclude other causes of treatment resistance.
authors.affiliation: Apotheek Haagse Ziekenhuizen, Den Haag. e.wilms@ahz.nl
authors.forename: E B
authors.initials: EB
authors.lastname: Wilms
authors.forename: R F
authors.initials: RF
authors.lastname: Veldkamp
authors.forename: E
authors.initials: E
authors.lastname: van Meegen
authors.forename: D J
authors.initials: DJ
authors.lastname: Touw
mesh_terms: D000074:Acenocoumarol / Q000008:administration & dosage / Q000627:therapeutic use; D000368:Aged; D000925:Anticoagulants / Q000008:administration & dosage / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D004351:Drug Resistance; D006801:Humans; D008297:Male; D006899:Mixed Function Oxygenases / Q000235:genetics*; D009203:Myocardial Infarction / Q000188:drug therapy; D010644:Phenprocoumon / Q000008:administration & dosage / Q000097:blood* / Q000627:therapeutic use; D011110:Polymorphism, Genetic; D016896:Treatment Outcome; D014812:Vitamin K / Q000097:blood; D064417:Vitamin K Epoxide Reductases
chemical_list: D000925:Anticoagulants; D014812:Vitamin K; D006899:Mixed Function Oxygenases; D064417:Vitamin K Epoxide Reductases; D000074:Acenocoumarol; D010644:Phenprocoumon