Warfarin is the oral anticoagulant most frequently used to control and prevent thromboembolic disorders. Warfarin, a coumarin derivative, inhibits vitamin K recycling by blocking its metabolism at the vitamin K-epoxide intermediate thereby decreasing the amount of available vitamin K. Warfarin has a narrow therapeutic index and large interpatient variability in the dose required to achieve target anticoagulation.
The aim of this study was to investigate the impact of PAI-1 polymorphism (5G/4G) on features of anticoagulant therapy in patients with heart valve replacement.
Materials and methods. The study included 155 patients with heart valve replacement (67.74% male, 32.26% women, average age (51.7±1.1) years. All patients received warfarine treatment from initial dose of 5 mg/day. We studied frequencies of polymorphic variants of PAI-1 gene and associations of individual reaction to warfarin intake with genotype of PAI-1 gene. For determination of polymorphic variant 5G/4G of PAI-1 gene the method of PCR-RFLP has been used.
Results. The frequencies of 5G/5G, 5G/4G and 4G/4G genotype among the patients group were 17.42, 52.26 and 30.32 %, respectively. The mean daily dose of warfarin was (3.23±0.26) mg in patients with 5G/5G genotype, (3.67±0.19) mg with 5G/4G genotype and (3.02±0.17) mg with 4G/4G genotype. The mean warfarin daily dose requirement was lowest in patients with genotypes PAI-1 4G/4G compared to patients with genotype 5G/4G (p<0.05). Duration of warfarin dose adjustment in patients with genotypes 5G/4G and 4G/4G was over two weeks more, than in patients with genotype 5G/5G.
Conclusions. Our results confirmed the role of PAI-1 polymorphism (5G/4G) in blood coagulation process and the importance of identifying the genotype of PAI-1 gene for warfarin dose adjustment.