Genetic Testing for the Prediction

of Anticoagulant Dose Requirement

Introduction

Coumarin derivatives, such as warfarin, phenprocoumon or acenocoumarol, are the most widespread oral anticoagulant drugs for the prevention and treatment of arterial and venous thromboembolic disorders. However, these vitamin K antagonists have a narrow therapeutic range and a wide inter-individual variability in dose requirement. Despite adjustment for clinical variables adverse events (delay in achieving a stable maintenance dose or bleeding complications) are frequently encountered during the initial phase of therapy. Genetic polymorphisms in the drug-targeted vitamin K epoxide reductase complex 1 (VKORC1) and in the drug metabolizing cytochrome P450 isozyme CYP2C9 have been reported to account for the majority of variations in the therapeutic response to warfarin.

Test Design

Mutations covered by the PGX-Thrombo Strip Assay are:

Gene      Polymorphism    Genotype   Coumarin Sensitivity

VKORC1    -1639 G>A              GG            low

                                                  GA            intermediate

                                                  AA            high

                   3730 G>A               GG            high

                                                  GA            intermediate

                                                  AA            low

                                                                   Metabolic Status

CYP2C9      430 C>T                 CC            extensive

                                                  CT            intermediate

                                                  TT            poor

                   1075 A>C               AA            extensive

                                                  AC            intermediate