OBJECTIVES Warfarin is a commonly prescribed anticoagulant drug used to prevent thromboses that may arise as a consequence of orthopedic and vascular surgery or underlying cardiovascular disease. Warfarin is associated with a notoriously narrow therapeutic window where small variations in dosing may result in hemorrhagic or thrombotic complications. To ultimately improve dosing of warfarin, we ...

Warfarin dosing is correlated with polymorphisms in vitamin K epoxide reductase complex 1 (VKORC1) and the cytochrome P450 2C9 (CYP2C9) genes. Recently, the FDA revised warfarin labeling to raise physician awareness about these genetic effects. Randomized clinical trials are underway to test genetically based dosing algorithms. It is thus important to determine whether common single nucleotide ...

BACKGROUND Pathogenesis of intraventricular hemorrhage (IVH) in premature infants is multifactorial. Little is known about the impact of genetic variants in the vitamin K-dependent coagulation system on the development of IVH. METHODS Polymorphisms in the genes encoding vitamin K epoxide reductase complex 1 (VKORC1 -1639G>A) and coagulation factor 7 (F7 -323Ins10) were examined prospectively ...

AIMS The study aims to evaluate the impact of genetic, demographic and clinical data on various measures of outcome of anticoagulation quality in patients. PATIENTS AND METHODS The study consisted of 310 patients receiving long-term oral anticoagulation therapy in our hospital. Apart from demographic and clinical variables, 21 SNPs (in 7 genes) were analyzed and compared with the outcomes of ...

Warfarin dose requirements have been associated with 2 main haplotypes in VKORC1, but the responsible polymorphisms remain unknown. To search for regulatory polymorphisms, we measured allelic mRNA expression of VKORC1 in human liver, heart, and B lymphocytes. The observed 2-fold allelic mRNA expression imbalance narrowed possible candidate SNPs to -1639G>A and 1173C<T. This genotype effect was ...

Warfarin is a commonly used anticoagulant, whose dose needs to be determined for each individual patient owing to large inter-individual variability in its therapeutic dose. Although several clinical and genetic variables influencing warfarin dose have been identified, uncovering additional factors are critically important for safer use of warfarin. Through a genome-wide association study, we i...

QUESTION UNDER STUDY Prospective validation of two algorithms for the initiation of phenprocoumon treatment. METHODS Inpatients with new-onset anticoagulation were randomised to one of two computer assisted dosing algorithms, or to a control arm. The primary outcome measure was the time to achieve therapeutic anticoagulation without overshooting (INR >4.0 within 10 days). Secondary outcomes i...

BACKGROUND Rodenticide resistance to anticoagulants in Rattus norvegicus will lead to increased difficulties in combating these pest animals. Here, the authors present the results of a survey in the Netherlands where tissue samples and droppings were tested using a newly developed TaqMan PCR test for genotypic variation at codon 139 in the Vkorc1 gene associated with anticoagulant rodenticide r...

Coumarin oral anticoagulant drugs have proven to be effective for the prevention of thromboembolic events. World-wide, warfarin is the most prescribed drug. In Europe, acenocoumarol and phenprocoumon are also administered. Yet it has been proven that variant alleles of the VKORC1 and CYP2C9 genotypes influence the pharmacokinetics and pharmacodynamics of these drugs. The combination of these tw...

Coumarins are widely prescribed worldwide, and in Mexico acenocumarol is the preferred form. It is well known that despite its efficacy, coumarins show a high variability for dose requirements. We investigated the pharmacogenetic variation of 110 genes in patients receiving acenocumarol using a targeted NGS approach. We report relevant population differentiation for variants on CYP2C8, CYP2C19,...