Standard warfarin dose in a patient with the CYP2C9*3/*3 genotype leads to hematuria.
BACKGROUND
Patients with certain CYP2C9 genetic variants have increased sensitivity to warfarin and are at increased risk of over-coagulation with standard warfarin dose. We report over-anticoagulation and hematuria manifest as a slow increase in the international normalized ratio (INR) due to warfarin treatment in a patient with the CYP2C9*3/*3 allele.


METHODS
A 58-y-old man with paroxysmal atrial fibrillation received a standard warfarin dose of 2.0mg/day. Because INR was 2.00 one week after treatment initiation, he was discharged from the hospital. One month later, hematuria was present and INR had increased to 7.26. Although in normal cases (R)-warfarin plasma concentrations are higher than (S)-warfarin, this patient had the opposite warfarin enantiomer plasma concentration profile.


CONCLUSIONS
Increased anticoagulation was due to an increased concentration of (S)-warfarin, the more active warfarin enantiomer. INR response to warfarin in this CYP2C9*3/*3 patient was slow. The later INR response appears to be strongly affected by CYP2C9 variants. He also had the VKORC1 -1639G>A AA genotype, requiring a lower warfarin dose. In this case, increased risk of bleeding could have been identified by prospective genotyping of CYP2C9 and VKORC1 prior to initiating warfarin therapy.
Goto
Toshiharu
T
Department of Pharmacy, Akita Medical Center, Akita, Japan.
Miura
Masatomo
M
Murata
Atsunobu
A
Terata
Ken
K
Uno
Tsukasa
T
Yamamoto
Koujirou
K
Abe
Yoshihisa
Y
D000925:Anticoagulants / Q000008:administration & dosage* / Q000009:adverse effects; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics*; D001281:Atrial Fibrillation / Q000188:drug therapy; D065729:Cytochrome P-450 CYP2C9; D005838:Genotype; D006417:Hematuria / Q000139:chemically induced*; D006801:Humans; D008297:Male; D008875:Middle Aged; D014859:Warfarin / Q000008:administration & dosage* / Q000009:adverse effects
D000925:Anticoagulants; D014859:Warfarin; C450260:CYP2C9 protein, human; D065729:Cytochrome P-450 CYP2C9; D001189:Aryl Hydrocarbon Hydroxylases