Warfarin

Warfarin belongs to a group of medications used to prevent blood clotting (these medications are called anticoagulants). Warfarin is used to prevent blood vessels from becoming blocked with blood clots, an event that can result in the obstruction of veins or in a heart attack. It is also used for the prevention and treatment of deep vein thrombosis. Setting the appropriate initial dosage is the major problem with warfarin prescription, as the right amount can greatly vary between individuals. Internal bleeding can occur in the case of the starting dosage being too high, and the initial dosage being too low, there is an increased risk of blood clotting. Generally, the appropriate initial dosage for each individual depends on their gender, age, body weight, and especially on the genetic code of the genes VKORC1 and CYP2C9, which determine the effectiveness of warfarin metabolism.

The mechanism of warfarin activity

Warfarin is a medication that inhibits the formation of the blood factors necessary for blood clotting, leading to a prolonged clotting time. The full effect of warfarin is monitored by measurements, which show the speed of blood clotting in the INR (international normalized ratio) units. The results of these measurements are apparent only after a few days of drug administration. Only then can your doctor adjust the warfarin dosage according to the results of the measurements.

The effect of warfarin depends on the age, weight, diet, effect of other drugs and on the genetic makeup, where the genes VKORC1 and CYP2C9 play an important role. VKORC1 encodes an enzyme which is normally suppressed by warfarin, and CYP2C9 encodes an enzyme which is responsible for warfarin metabolism. Research has shown that it might be necessary to raise or lower the initial dosage of warfarin as much as 40 per cent depending on individual genetic makeup. A mutation in the VKORC1 gene causes the production of a less active enzyme. For people with this genetic makeup a lower starting dosage of warfarin is needed. The gene variants of CYP2C9*2 and CYP2C9*3 significantly reduce the rate of warfarin metabolism, resulting in higher concentrations of the drug in the blood, and consequently also a lower dosage of warfarin necessary in the beginning of treatment.