Malezhik L.P

Chita State Medical Academy, Chita, Russia

HAEMOSTASIS IN ACUTE RESPIRATOR VIRAL INFECTIONS IN FREQUENTLY ILL CHILDREN WITH POLYMORPHISM GENE (Asp299Gly) TOLL-4 AND (Ser249Pro) TOLL-6 RECEPTOR

Basis protection of organism with palindromic ari realization of immunity system. The haemostatic without accompany of immune reactions. This systems functional correlation. However the state of the haemostatis system with acute respiratory viral infections eхamine insufficiency. The eхamine haemostasis in children with palindromic ari and genetic defects in the Toll-4 ( Asp299Gly) and Toll-6 (Ser249Pro) receptors absence.

Purpose - to examine the state of the hemostatic system in children with palindromic ari and polymorphism of Toll-4 (Asp299Gly) and Toll-6 (Ser249Pro) receptors.

Materials and Methods: A total of 190 children from 1 to 3 years, with frequent episodes of acute respiratory infections (ARI) were eхamined.

The control group consisted of healthy children from 1 to 3 years with the number of episodes of ARI was not more than 4 per year.

Of the patients 90 children were carriers of the gene polymorphism (Asp299Gly) Toll-4 receptor, and 100 carriers of mutations in the gene (Ser249Pro) Toll-6 receptor.

Children with palindromic ARI and genetic defects blood sampling was performed at admission, which were determined coagulation and fibrinolytic activity by conventional methods.

All data were eхpressed as mean ± SD. Differences between control children and patients were analysed by Student’s t-test. Overall statistical significance was set at p<0,01.

Resalt. The studies found that children with frequent episodes of acute respiratory viral infection develops during the next hypercoagulability, which is expressed by the shortening of plasma recalcification time, aPTT, fibrinogen, and increasing concentration of the fibrin monomer complex (SFMC). Against the background of rapid formation of fibrin was depressed fibrinolysis (Table 1).

The main cause of hypercoagulability with SARS were antigenic activation of immune cells and destruction of affected tissues. Cytolytic effects with allocation prokoagulyatnyh and fibrinolytic compounds caused by viruses, the complement system, cytotoxic lymphocytes, NK-cells.

In addition, activation of cells involved in inflammation, there is a structural movement of membrane molecules of "blebbing" with the expression on the surface of tissue factor, which initiates the formation of prothrombinase on the external mechanism.

We analyzed the possibility of such a reaction, and to determine whether expression of tissue factor in the blood of children with SARS. It turned out that the phagocytes of sick children is significantly faster than control cells, accelerate blood clotting, which can be one of the causes of hypercoagulability in blood flow in respiratory infections.

According to modern concepts, tissue factor may be expressed not only on the surface of intact cells, but also be on the microvesicles, otshnurovannyh from the cell membrane.

When genetic defects in membrane receptors (Toll-4) expression of tissue factor expressed greater than similar cells with normal structure of signaling receptors.

In addition, holders of polymorphic variants of the gene Toll-4 receptor concentration of fibrinogen, SFMC level higher than that of similar ill children with normal allele 299 Asp. Against the background of rapid formation of fibrin slowed fibrinolysis, especially in carriers of heterozygous mutant (Asp299Gly) and the replacement allele homozygotes (299Gly).

Such changes in hemostasis identified and pediatric patients with polymorphisms Toll-6 (Ser249Pro) receptor. They have high blood concentrations of fibrinogen, SFMC.

Euglobulinovy fibrinolysis lengthened in heterozygotes (Ser249Pro) by 12.5% compared with homozygous carriers of the normal and 32% for the holders of the mutant allele homozygotes with 249Pro. Tissue factor expression on cells with a genetic defect in the Toll-6 receptor is expressed to a greater extent than those of the same children, but no abnormalities in the signaling receptors.

Consequently, for the polymorphism of genes Toll-4 and Toll-6 receptor hypercoagulability in children with SARS expressed to a greater extent than those of the same children, but without the genetic mutations in the receptor signaling.

Table 1.

Coagulation tests results of the childrens with palindromic ARI ( M± SD)

Tests Chealthy control Patients

Time recalcificans (sec.) 110,0 ± 3,6 87,8 ± 4,9*

aPTT(sec.) 32,6 ± 0,2 30,3 ± 0,9*

MNO 1,00 ± 0,01 1,3 ± 0,2

Fibrinogen (gr./l.) 3,0 ± 0,3 4,2 ± 0,4*

Fibrinolys ( min.) 211,3 ± 5,3 257,2 ± 13,2*

SEMS ( mg.%) 3,38 ± 0,02 6,2 ±1,1*

Eхpression of tissue 101,0 ± 9,2 77,7 ± 5,6*

factor monocytes (sec.)

* - The p-value differences between patients and control group.