GENETIC FEATURES OF RESISTANCE TO ANTITHROMBOCYTIC DRUGS IN PATIENTS WITH ISCHEMIC HEART DISEASE AFTER CONDUCTED PERCUTANEOUS CORONARY INTERVENTION

Abstract

The aim of the study: To study and evaluate platelets aggregation activity as primary phase of haemostasis and anti-platelet therapy in IHD patients after PCI, depending on the polymorphism of the gene ITGA 2 - C 807T.

Materials and methods: 54 patients who were on a treatment at the clinical hospital "Feofaniya" (Kyiv) and at the Kyiv Clinical Hospital on railway transport №2 were examined: 20 women and 34 men (mean age - 67.8 ± 7.46 years). The study involved patients with stable forms of coronary artery disease (stable angina pectoris II-III) and acute coronary syndrome, with a history of percutaneous coronary intervention (PCI). All patients received antiplatelet therapy: acetylsalicylic acid (3.7%), clopidogrel (9.3%) or a combination of them (87%).

Functional activity of the platelets was studied on a Biola Aggregation Analyzer laser agrometer. The response to antiplatelet therapy was confirmed by the Aggredyne test. The polymorphism of the C807T of the ITGA2 gene was determined by polymerase chain reaction (PCR).

Based on the results of the aggregation ability, antiplatelet therapy sensitivity, the patients were divided into two groups: group I - individuals with varying degrees of insensitivity to antiplatelet drugs (35 patients), group II - susceptible to treatment (19 patients). In each group was analyzed the polymorphism of the gene ITGA2 and features of the functional activity of the platelets, depending on the genotype.

Results: In 50% of patients receiving ASA there was a different degree of non-sensitivity, with respect to thienopyridines - this figure was 20%. Among patients who received dual antiplatelet therapy did not match at least one of the drugs - 83.3%. Among the "non responders" 78.9% had a mutated T-allele, and a homozygous variant for the T allele was recorded in 53.15% of patients, while "respondents" - 15.8%. Most in the group of "respondents" was the group of the native genotype - C / C. The most pronounced tendency to influence the genotype on spontaneous aggregation was observed in relation to the T-allele, in particular in the homozygote (genotype T / T). The significant difference between the groups was obtained from the platelet response to ADP. Thus, the reaction of carriers in the T-allele, as homo- and heterozygotes, was significantly different.

Conclusions: In 64.8% of patients with coronary heart disease after PCI was observed a decrease in antiplatelet sensitivity, which has a clear link with the polymorphism of the gene ITGA 2. The presence of the T-allele in the genotype of patients with IHD is associated with a less adequate platelet response in patients receiving dual antiplatelet therapy for ASA and thienopyridines on ADP, which may have an effect on the sensitivity to thienopyridines.