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Early acenocoumarol overanticoagulation among cytochrome P450 2C9 poor metabolizers

Verstuyft, Célinea; Morin, Sandrinea; Robert, Annieb; Loriot, Marie Annec; Beaune, Philippec; Jaillon, Patricea; Becquemont, Laurenta

Short Communication
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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.

aPharmacological Department, Saint Antoine University Hospital, Paris, bHaemostasis Department, Saint Antoine University Hospital, Paris and cINSERM U490, Centre Universitaire des Saint Pères, Paris University, Paris, France

Correspondence to Dr Laurent Becquemont, Service de Pharmacologie, Faculté de Médecine Saint Antoine, 27 rue de Chaligny, 75012 Paris, France Tel: +33 1 40 01 14 33; fax: +33 1 40 01 14 04; e-mail: laurent.becquemont@chusa.jussieu.fr

Received 15 December 2000;accepted 28 March 2001

© 2001 Lippincott Williams & Wilkins, Inc.