Warfarin Dosing (CYP2C9/VKORC)
Warfarin is the most commonly prescribed oral anticoagulant. It is used to prevent harmful clotting after heart attack, stroke or major surgery.
The therapeutic dose of Warfarin for each patient can vary greatly and be hard to predict. If the dose is incorrect, excessive bleeding can occur with too much Warfarin, while too little may result in harmful clot formation.
Traditionally, doctors would use the patient's sex, age, weight and medical history to determine the initial Warfarin dose. However, these characteristics do not account for the major sources of variation in doses required. Therefore, a patient will need to have blood tests (ie INR) for many weeks or even months to determine the true individual dose. This can be a lengthy trial and error process, and you may be at an increased risk of an adverse reaction until the correct dose is found.
The major functional components that influence the Warfarin dose are:
- How rapidly a person can metabolise (or clear) Warfarin. (Metabolism)
- How much Warfarin is required to inhibit the clotting process? (Action)
Warfarin Clearance (metabolism)
Warfarin is metabolized by the Cytochrome p450 2C9 enzyme (CYP2C9). Up to 35% of patients have inherited a form of the enzyme with reduced activity. When this deficiency is present in a patient, Warfarin is cleared more slowly, leading to high blood levels which then increases the risk of excessive bleeding.
Two genetic variants can lead to a reduced activity of CYP2C9. They are known as CYP2C9*2 and CYP2C9*3.
Warfarin Action
Warfarin inhibits the formation of active clotting factors by inhibiting vitamin K. DNA sequence differences in the VKORC1 gene increase or decrease the amount of warfarin required to inhibit the formation of clotting factors.
Pharmacogenetics and Warfarin Dose Variability
Since CYP2C9 and VKORC1 act independently, the total genomic based Warfarin variability is presently believed to be at least 50%. Variants in these genes lead not only to variable initial Warfarin dose sensitivity but also to delays in achieving a stable maintenance dose.
How to Use these Tests
CYP2C9 and VKORC1 gene testing can now explain why certain people require a lower or higher dose of Warfarin to get its full benefits. This genetic information can help doctors determine each patient's individual Warfarin dose more quickly and precisely.
Advantages of Genotyping in Predicting Warfarin Maintenance Doses
By determining the genotype of CYP2C9 and VKORC1 your doctor can now more accurately set the Warfarin maintenance dose thereby minimizing possible adverse reactions such as excessive bleeding or harmful clot formation. By using genotyping information a persons Warfarin therapeutic steady state level is reached more quickly thereby reducing the period of trial and error.
| Medicare Rebate available: | No, this test is not covered by Medicare |
| Specimen Type required: | Blood or mouth swab |
| Results available from your Doctor: | 3-5 days |