Early acenocoumarol overanticoagulation among cytochrome P450 2C9 poor metabolizers.
Cytochrome P450 2C9 (CYP2C9) is the enzyme that terminates the anticoagulant effect of warfarin. The heterozygous carriers of the two allelic variants CYP2C9*2 and CYP2C9*3 have been associated with impaired warfarin metabolism and a higher risk of haemorrhage. Only three CYP2C9 poor metabolizers (CYP2C9*3/CYP2C9*3) initiating warfarin treatment have so far been identified, all of them with a dramatic overdose occurring a few days after treatment initiation. Acenocoumarol, another coumarinic anticoagulant, has recently been shown to be metabolized by CYP2C9. We report, for the first time, two cases of dramatic overanticoagulation occurring in patients starting acenocoumarol treatment while taking recommended doses (4 mg/day). In both cases, the overdose was discovered at the first INR control with values above 9. Genotyping revealed that the two patients were homozygous for the CYP2C9*3 allele. Our report highlights the need for CYP2C9 genotyping before starting oral anticoagulants in order to prevent early overanticoagulation episodes.
Verstuyft
C
C
Pharmacological Department, Saint Antoine University Hospital, Paris, France.
Morin
S
S
Robert
A
A
Loriot
M A
MA
Beaune
P
P
Jaillon
P
P
Becquemont
L
L
D000074:Acenocoumarol / Q000009:adverse effects* / Q000627:therapeutic use; D000293:Adolescent; D000368:Aged; D000369:Aged, 80 and over; D000925:Anticoagulants / Q000009:adverse effects* / Q000627:therapeutic use; D001189:Aryl Hydrocarbon Hydroxylases; D001778:Blood Coagulation Disorders / Q000139:chemically induced / Q000201:enzymology* / Q000235:genetics; D065729:Cytochrome P-450 CYP2C9; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics* / Q000378:metabolism*; D005260:Female; D006801:Humans; D019934:International Normalized Ratio; D009154:Mutation / Q000187:drug effects / Q000235:genetics; D039181:Steroid 16-alpha-Hydroxylase; D013250:Steroid Hydroxylases / Q000235:genetics* / Q000378:metabolism*
D000925:Anticoagulants; D003577:Cytochrome P-450 Enzyme System; D013250:Steroid Hydroxylases; C450260:CYP2C9 protein, human; D065729:Cytochrome P-450 CYP2C9; D001189:Aryl Hydrocarbon Hydroxylases; D039181:Steroid 16-alpha-Hydroxylase; D000074:Acenocoumarol