[Factors influencing the variable response to treatment with oral anticoagulants]

During therapy with oral anticoagulants, which are the main drugs used for treatment and prevention of thromboembolic diseases, there is significant variability in individual doses required to achieve the therapeutic effect. Oral anticoagulant therapy requires regular monitoring of INR, which should be within the range of 2-3. Currently there is no reliable test predicting which patient will require an extremely high or low dose of these drugs. The variability of responses to oral anticoagulants is regulated by demographic factors such as age, sex, body mass; environmental factors and genetic factors. The personal factors include medication, diet, coexisting systemic diseases. Among genetic factors the most important are polymorphisms of two genes which take part in metabolism of vitamin K and oral anticoagulants. These are: a gene encoding CYP2C9, an enzyme which is involved in hepatic metabolism ofcoumarin derivatives and vitamin K epoxide reductase complex subunit 1 (VOKRC1), the target enzyme of action of oral anticoagulants. Less important are mutations in genes encoding other subunits of cytochrome P450, vitamin K dependent clotting factors, calumenin, gamma-glutamyl carboxylase, apolipoprotein E and microsomal epoxide hydrolase. All these factors can affect both the pharmacokinetics and pharmacodynamics of coumarin derivatives. Considering the main genetic and environmental factors we can predict the dose of oral anticoagulants required in about two-thirds of cases.