More details about warfarin efficacy

Warfarin inhibits the enzyme (vitamin K epoxide reductase), which recycles vitamin K to active form, which is needed for synthesis of some blood clotting factors. Thus, there are less clotting factors present in blood and the blood clotting time is prolonged. The maximum effect of warfarin is reached after a few days, when the existing clotting factors that were present in the blood before warfarin was given, become metabolised.
A physician prescribing warfarin must monitor its blood-thinning effect by frequent blood-testing, using the International Normalized Ratio (INR) test. On the basis of results from these tests, the physician must adjust the dose of warfarin to ensure the desired therapeutic level of blood thinning. The effect of warfarin is dependent also on many other factors such as age, weight, diet and other drugs.

Genotype affects warfarin

Beside aforementioned factors, two genes also affect warfarin efficacy in a patient. These are the gene, which codes the target enzyme (VKORC1) and gene, which codes the warfarin metabolising enzyme (CYP2C9). Research on 1500 patients showed, that genetic factors account to 40% difference in average starting dose of warfarin, while other non-genetic factors account for only 15%. Some VKORC1 gene polymorphisms change the property of this enzyme; therefore it becomes less active than in the general population. These people need a lower than average dose of warfarin. On the other hand CYP2C9*2 and CYP2C9*3 versions of CYP2C9 gene lower the metabolising rate of warfarin. Thus, more warfarin is present in blood. These patients also require lower than average dose.
Depending on the gene combination, a patient needs higher or lower starting dose of warfarin. This information about gene variation is very important for a physician when first prescribing warfarin.

Back to basic description