FP788
PARTICIPATION OF HEREDITARY RISK FACTORS FOR PATHOLOGICAL THROMBUS FORMATION IN THE DEVELOPMENT OF ATYPICAL HEMOLYTIC-UREMIC SYNDROME IN CHILDREN

INTRODUCTION AND AIMS: Atypical hemolytic-uremic syndrome (aHUS) is a life-threatening chronic disease, which is based on a genetically determined defection of the system of regulation of the compliment. Predisposition to the development of thrombotic damage have both acquired and hereditary causes. We assume that intravascular hypercoagulation can be the risk factor of microvascular thrombosis in HUS.The aim was to investigate the association of аHUS and genetically associated thrombophilia in children.

METHODS: 23 children with аHUS from 2,5 months to 16 years old (15 girls and 8 boys, mean age 5,5±3,9 years) were examined. Polymorphism of a number of coagulating blood system genes, such as FGB, F2, F5, PAI-1, ITGA2, ITGB3, MTHFR: 677 C>T, MTHFR: 1298 A>C, MTR, MTRR were studied using molecular genetics methods (PCR-mass spectrometry, PCR-restriction analysis).

RESULTS: We revealed polymorphism of examined genes in all children with aHUS. Polymorphism of singular gene was found only in 2 (8.7%) patients (FGB/MTHFR: 677 C>T). Most of the patients (91.3%) had multigene form of thrombophilia: polymorphisms of 2 genes was revealed in 1 patient (4.8%), in 20 cases (95.2%) three and more. Polymorphism of genes PAI-1 and MTRR turned out to be more often and was registered in 90.5% and 81% cases, accordingly. Homozygotic carrier state of mutant allele of gene MTRR was found in 5 patients (29.4%), heterozygous in 12 cases (70.6%), of gene PAI-1 in 6 patients (31.6%) and 13 patients (68.4%), accordingly, of gene FGB in 2 cases (15.4%) and 11 cases (84.6%), accordingly, of gene ITGA2 - in 3 cases (25%) and 9 cases (75%), accordingly, of gene MTHFR: 677 C>T - in 2 cases (16.7%) and 10 cases (83.3%), accordingly, of gene MTR in 2 cases (22.2%) and 7 cases (77.8%), accordingly. Leyden mutation (F5) was found in 2 patients, polymorphism of gene MTHFR: 1298 A>C in heterozygous form - in 10 cases and in any case not detected polymorphism F2 gene. Multigene form of thrombophilia was characterized by combination of polymorphism of genes FGB, PAI-1, ITGA2, ITGB3 in 3 patients (14.3%), in 4 cases (19%) - combination of 5 mutant allele (FGB, PAI-1, MTHFR: 1298 A>C, MTR, MTRR).

CONCLUSIONS: Thus, such a high rate of polymorphisms of coagulating blood system genes at aHUS gives grounds to consider hereditary thrombophilia as a risk factor of thrombotic microangiopathy development. This fact confirms the validity of the hypothesis of multiple strikes in the implementation of complement-mediated TMA.