The PGX-Thrombo StripAssay identifies a common polymorphism (-1639 G>A) in the VKORC1 promoter and two functionally impaired CYP2C9 variants (2 and 3).
Vitamin K antagonists (coumarins) are the most widely used oral anticoagulants for the prevention and treatment of venous thromboembolism, myocardial infarction and stroke. However, their narrow therapeutic range and wide inter-individual variability in dose response contribute to a considerable risk of adverse events during the first weeks to months of therapy. An inappropriate dosage can result in life-threatening complications, such as major bleeding in case of an overdose or incomplete prophylaxis from an insufficient dose. Careful monitoring of blood coagulation by measuring the prothrombin time, expressed as International Normalized Ratio (INR), is essential until a stable maintenance dose has been achieved. Coumarin derivatives, such as warfarin (Coumadin®), phenprocoumon (Marcumar®) or acenocoumarol (Sintrom®), exert their therapeutic effect through inhibition of the vitamin K epoxide reductase. Polymorphisms in the target gene vitamin K epoxide reductase complex subunit 1 (VKORC1) are known to affect coumarin sensitivity. Moreover, variable rates of coumarin turnover due to polymorphisms in the drug metabolizing cytochrome P450 isozyme CYP2C9 also contribute to individual dose requirements. The benefits of a pharmacogenetic approach to anticoagulation therapy are a more accurate a priori estimation of the coumarin maintenance dose, a decreased risk of inappropriate dosing during induction of therapy, and a reduction in time to achieve stabilization of therapy. A pharmacogenetic test for the prediction of coumarin dose requirements may therefore enable clinicians to provide a safer and more individualized anticoagulant treatment to their patients.