The Pharmaceutical Journal
Vol 268 No 7193 p487-492
13 April 2002

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Journal of the American Medical Association (jama.ama-assn.org)

Genetic variation causes increased warfarin side effects

Patients with specific genetic variations are at increased risk of bleeding events and are less stable on maintenance therapy with warfarin, researchers have found.

Dr Mitchell Higashi, University of Washington Medical Centre, and colleagues investigated the relationship between genotype and anticoagulation status in 185 patients on long-term warfarin therapy. At least one variation in the CYP2C9 allele, involved in the metabolism of warfarin, was found in 31 per cent of patients.

The researchers found that mean maintenance dose was related to genotype and that having the variant genotype led to a higher bleeding rate.

"Patients with variant CYP2C9 alleles become over-anticoagulated at a faster rate and must undergo additional dose adjustments, thus translating into a longer time until stable dosing is achieved. When these patients do become stable, their daily maintenance dose of warfarin is significantly lower than that of patients without genetic impairment of warfarin metabolism," the researchers say.

They comment that treatment guidelines are likely to need updating as genomic information becomes more readily available. Patients with variations in CYP2C9 alleles could be considered for lower doses of warfarin when therapy is initiated and might also be candidates for increased surveillance for bleeding risk (JAMA 2002; 287:1690).