Distribution of prothrombotic polymorphisms in children with microcirculatory type of bleeding on the background of undifferentiated connective tissue dysplasia

Abstract

Introduction. In patients with microcirculatory type of bleeding on the background of undifferentiated connective tissue dysplasia (UCTD), along with a tendency to bleeding, genetic predictors of thrombogenic risk are identified. Materials and methods. DNA samples of 92 adolescents (55 boys and 37 girls) aged from of 6 months to 18 years were used. The control group consisted of 115 children (I-II health groups). The analysis was based on the Real-Time PCR method using competing TagMan probes. The genetic testing of 12 allelic DNA polymorphisms was carried out. There was performed the analysis of laboratory and instrumental methods. The results were statistically processed with using the StatSoft Statistica 6.1 software package. Results. There was determined an increased prevalence of occurrence of the minor G(-455) allele of the gene of FGB fibrinogen, the minor allele (C807) of the gene of platelet receptor for ITGA2 collagen, and the rare homozygous 4G (-675) allele of the PAI-1 gene in patients compared with healthy children. Homozygous genotype (rare allele) 807TT of the ITGA2 gene of the platelet receptor for collagen and homozygous genotype 4G(-675)4G of the PAI-1 gene in patients with bleeding manifestations on the background of UCDT were detected significantly more often than in healthy children. In 76 (82.6%) children there were detected phenotypic signs of UCDT, their average number for each patient was of 3.2 ± 0.7. In the blood of sick children, there was a decrease in platelet aggregation by 2 and 3 inducers (epinephrine, ADP, collagen) and an increased concentration of homocysteine. Conclusion. The detection of hidden genetic predictors of thrombogenic risk in patients with microcirculatory type of bleeding against the background of UCDT is an indication for personification of treatment, since with an increase in the predictors of thrombophilia in such patients, the risk of thrombosis increases. In this case, the state of thrombotic or hemorrhagic predisposition should be determined in a timely manner, and hemostatic therapy with drugs that do not provoke thrombosis should be used against the background of angioprotectors.