TY - JOUR
T1 - Major bleeding caused by warfarin in a genetically susceptible patient
AU - Bloch, Aharon
AU - Ben-Chetrit, Eldad
AU - Muszkat, Mordechai
AU - Caraco, Yoseph
PY - 2002
Y1 - 2002
N2 - A 90-year-old woman was hospitalized for gastrointestinal bleeding. Although she had been receiving only warfarin 5 mg/day, her international normalized ratio (INR) was 66. Warfarin was discontinued, and her INR fell to 3.7 after transfusion of fresh-frozen plasma. However, it rose again spontaneously to 7.5. Eleven days after the last dose of warfarin had been administered, it was still detectable in the patient's plasma, indicating that impaired warfarin clearance may have caused an enhanced anticoagulation effect. Genetic analysis of the cytochrome P450 (CYP) isoenzyme 2C9, which mediates the major deactivating pathway of S-warfarin, revealed that the patient was a compound heterozygote carrying two variant alleles: CYP2C9*2 and CYP2C9*3. The patient's enhanced sensitivity to warfarin 5 mg/day can be ascribed to decreased clearance of S-warfarin secondary to genetic alteration of the gene encoding CYP2C9, resulting in a life-threatening complication.
AB - A 90-year-old woman was hospitalized for gastrointestinal bleeding. Although she had been receiving only warfarin 5 mg/day, her international normalized ratio (INR) was 66. Warfarin was discontinued, and her INR fell to 3.7 after transfusion of fresh-frozen plasma. However, it rose again spontaneously to 7.5. Eleven days after the last dose of warfarin had been administered, it was still detectable in the patient's plasma, indicating that impaired warfarin clearance may have caused an enhanced anticoagulation effect. Genetic analysis of the cytochrome P450 (CYP) isoenzyme 2C9, which mediates the major deactivating pathway of S-warfarin, revealed that the patient was a compound heterozygote carrying two variant alleles: CYP2C9*2 and CYP2C9*3. The patient's enhanced sensitivity to warfarin 5 mg/day can be ascribed to decreased clearance of S-warfarin secondary to genetic alteration of the gene encoding CYP2C9, resulting in a life-threatening complication.
UR - http://www.scopus.com/inward/record.url?scp=0036138789&partnerID=8YFLogxK
U2 - 10.1592/phco.22.1.97.33491
DO - 10.1592/phco.22.1.97.33491
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C2 - 11794436
AN - SCOPUS:0036138789
SN - 0277-0008
VL - 22
SP - 97
EP - 101
JO - Pharmacotherapy
JF - Pharmacotherapy
IS - 1
ER -