Warfarin is the most widely used oral anticoagulant and is among the most effective agent to prevent thromboembolic events in a variety of clinical settings.
It is scientifically established that CYP2C9 genetic polymorphisms affect warfarin metabolism whereas VKORC1 genotype cause a significant difference in warfarin sensitivity index.
In this context, the Food and Drug Administration (FDA) approved a labeling change for warfarin that describes the effects of VKORC1 and CYP2C9 genetic variants on warfarin dose requirements. Also, the Clinical Pharmacogenetics Implementation Consortium (CPIC) of the National Institutes of Health Pharmacogenomics Research Network develops peer-reviewed gene–drug guidelines that are published and updated periodically based on new developments in the field.
INDICATION FOR WARFARIN PHARMACOGENETIC TESTING
- For individuals with a personal or family history of adverse drug reactions to warfarin.
- When prescribing warfarin in a clinical context of thromboembolic diseases, pulmonary thromboembolism, stroke or myocardium infarction among others.
WHAT IS EVALUATED IN THE PHARMACOGENETIC TESTING?
CYP2C9 and VKORC1 genetic variants influence the half-life of warfarin and the time to achieve a stable dose.
CYP2C9 is an important drug-metabolizing enzyme that catalyzes the biotransformation of warfarin. About 35% of Caucasians have a slow acting form of this enzyme. Genetic variants of VKORC1 increase or decrease the amount of warfarin needed to inhibit the formation of the clotting factors. By evaluating these genetic variants it is possible to evaluate the sensitivity to warfarin and so to prescribe an adequate dose.
BENEFITS OF GENETIC TESTING
Avoid warfarin side-effects by prescribing a tailored dose according to each individual genetic profile
Warfarin efficacy is highly dependent on achieving and maintaining a narrow therapeutic window, usually an International Normalized Ratio (INR) between 2 and 3. Its use can be associated with increased risk of blood clot formation when treatment is subtherapeutic (INR of less than 2) or bleeding when supratherapeutic (INR of 4 or more).
The genetic test evaluates the genotypes that affect the metabolism of warfarin.
Obs: The results of the genetic testing should be interpreted in the context of the patient’s medical evaluation, family history and racial/ethnic background.
REQUEST A TEST:
- Warfarin Pharmacogenetics (2 genes)
- TromboGene (Genetic Evaluation of Hereditary Thrombophilia)
+ Warfarin Pharmacogenetics (12 genes)
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This article was published on February 2, 2015.