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.

CASE: 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.