138 - Genetic variables and their influence on oral an- ticoagulant therapy

Autor(s): A. Tosetto

Issue: RIMeL - IJLaM, Vol. 5, N. 2, 2009 (MAF Servizi srl ed.)

Page(s): 138-143

Oral anticoagulation therapy is the mainstay for both primary and secondary prophylaxis of venous and arterial thromboembolism. The main drawback of this therapy is its wide interindividual variation, that requires a careful clinical and laboratory monitoring, particularly during the first weeks of therapy (known as induction phase). Recently, some genetic polymorphisms have been described as partially explaining this variability. In particular, polymorphisms in the VKORC1 and in the CYP2C9 genes, encoding the epoxido-reductase and cytochrome P2C9 enzymes have been shown to be strongly associated with warfarin requirements. Various studies have addressed the role of these two polymorphisms on the prediction of warfarin requirement, suggesting that these polymorphisms may be useful to reduce the time to target INR and number of episodes with excessive anticoagulation during the induction phase. These advantages are possibly more evident in those patients requiring very high or very low doses of warfarin, less so in those patients requiring standard warfarin doses. At present, however, the burden of added costs and the lack of evidence for a reduced number of bleeding or thrombotic complications does not recommend a routine use of these polymorphisms in the clinical practice. Key-words: Warfarin, Genotype, Anticoagulants, CYP2C9 protein, Vitamin K epoxidase, Mixed function Oxy- genases/genetics, Aryl hydrocarbon hydroxylases/genetics.

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