engleski

Bleeding as a complication of warfarin therapy

Cytochrome P450 CYP2C9 is the main enzyme for metabolism of S-warfarin, which is the drug of choice among oral anticoagulants. The aim of the study was to determine the association of bleeding as the most important complication of warfarin therapy with CYP2C9 polymorphism, warfarin dose, INR at induction, and underlying illnesses. The study included 181 patients (102 women and 79 men) treated with warfarin for at least a month. According to the bleeding events the patients were divided into the three subgroups: without, with minor and with major bleeding. According to the daily warfarin dose they were divided into the two groups: dose of 1.5 mg or less (n=24) and dose of more than 1.5 mg (n=157). According to the INR at induction they were divided into the three subgroups: 3.5 or less, between 3.6 and 5.0 and more than 5.0. Genotyping of cytochrome P450 CYP2C9 (alleles *1, *2 and *3) was performed by PCR-RFLP procedure. One hundred and sixtythree of the 181 patients were free of bleeding (90.1 %), minor bleeding occurred in 14 (7.7%) patients and 4 patients (2.2%) experienced major bleedings. Bleeding occurred more frequently in those taking 1.5 mg or less of warfarin. Subgroups according to the genotype did not differ significantly in bleeding events frequency. Presence of *1 allele was not a risk for bleeding event, neither was presence of *2 allele nor *3 allele. Bleeding occurred the most frequently in the subgroup of patients with INR more than 5.0. The subgroups of patients divided according to the bleeding events differed significantly in the optimal warfarin dose. The subgroups of patients according to the underlying illnesses did not differ in the bleeding frequency.

CYP2C9 polymorphism; warfarin; bleeding

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