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Section 7. Medical science
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Salikhova Kamola Shavkatovna, Head of department Republican Specialized Scientific-Practical Medical Center of Pediatrics E-mail: [email protected]
Relationship between some indices of the cytokine system and haemostasis at low birth weight infants
Abstract: The work performed in order to study the complex dynamics ofhemostatic parameters in the first week of life in low birth weight infants, and comparing them with the features of the cytokine spectrum. There were conducted examination the state of hemostasis and the content of TNF and IL1b in 20 healthy full-term newborns and 68 low birth weight infants at the early neonatal period. Analysis of the dynamics of certain hemostatic parameters testifies the variability ofthese parameters at different stages in the early neonatal period in low birth weight infants. At low birth weight infants tensions in the hemostatic system is observed from the first days after birth. Pro-inflammatory cytokines, along with other factors, lead to increase the tension in all hemostatic system and dysfunction of endothelium.
Keywords: cytokines, the endothelium of blood vessels, hemostasis, newborns.
The early neonatal period life of the child represents a nation of extreme influences, demanding continuous change
unique combination of extreme impacts, requiring continuous change of adaptation mechanisms to the functional, hormonal and biochemical and immunological levels. In the process of adaptation to extrauterine life in the hemostatic system of the newborn dynamic changes taking place, which should not exceed the physiological limits, but the combination of multifactor extreme conditions disrupted the balance in the system. Among such extremal effects refers the prematurity, low birth weight, which is peculiar to immunological disorders [3; 7; 8; 9].
There is extensive information about cytokines now. Cytokines having multifunctionality, provide all phases of the inflammatory, hemostatic and immunological processes until recovery, that is, they are able to perform and immu-
nostimulatory (proinflammatory and immunosuppressive) anti-inflammatory, hematopoietic function [12]. The spectrum of effects of interleukins including: induction of IL-2, colony stimulating factors, synthesis of acute-phase proteins, of which is pro- and anticoagulants products IgA, IgM, IgG, induces maturation of megakaryocytes, osteoblasts, and macrophages, neuronal differentiation. On the other hand, they also induce apoptosis of neutrophils possessing anti-inflammatory properties. A special place in the regulation of blood coagulation activity of endothelial belongs that is modulated by cytokines: tumor necrosis factor (TNF-a, IL-1^) [1; 5]. They participate in generating a large amount of tissue thromboplastin of all vitamin K-dependent factors [7; 11]. Among the challenges of modern neonatology are insufficiently studied issues relating to the formation of the hemostatic system in LBW newborns in the early neonatal period, since the combi-
of adaptation mechanisms on the functional, hormonal, biochemical levels affect this process [2; 4; 6; 8]. Considering the above stated the purpose of work was to study the complex dynamics of hemostatic parameters in the first week of life in low birth weight infants, comparing them with the features of the cytokine spectrum.
Materials and methods. We conducted a clinical and laboratory (state of hemostasis and cytokine TNF-a and IL-1^) examination at the early neonatal period in 20 healthy full-term newborns and 68 low birth weight infants. The age of mothers of surveyed children in both groups was identical: ranged from 20 to 35 years, on average, 25.2±0.6 years.
In addition to clinical research methods, there have been conducted special research methods: the standardized partial thromboplastin time (aptt), using reagents firm "renamo" (Russia); determination of prothrombin time according to quick; determination of fibrinogen by using koagulometers sets «human diagnostics worldwide (geramaniya); determination of thrombin time using the reagent kit of the company "renamo" (Russia); determination of the amount of cytokines, tnf, IL-1^-elisa-test systems using ltd. "cytokine"
Results of the study
Analysis of the survey results showed that in 48.9% of the surveyed women have chronic diseases without exacerbation during pregnancy (chronic tonsillitis, chronic pyelonephritis, diffuse nontoxic goiter). From obstetric history in group 1 revealed that 39.4% of women - primigravida, 22.8% - again primiparous pregnant, 37.8% - multiparous. In 15% of the mothers was observed anemia 1 and 2 degrees, 25% have been observed toxicosis of 1st half. All Group 1 chil-
Relationship between some indices of the cytokine system and haemostasis at low birth weight infants
dren born at line 39-40 weeks gestation, weighing an average of 3576±0,59 g and a body length on average 51.4± 0.2 cm. Apgar score was at 1 minutes into the 7-9, 5 minutes - 8-9. Condition at birth for all children was satisfactory. In the analysis of obstetric history two groups we found a variety of diseases in mothers, the consequences of which are unconditional chronic intrauterine fetal hypoxia. When analyzing the data of pregnancy revealed that toxicosis 1st half of pregnancy were observed in 72% of women, gestosis 2nd half of pregnancy in 22% of threatened abortion, 16% of women. In 75% of women with anemia pregnancy was I-II degree. The children were born on 30-34 weeks gestation. A natural way resolved 80% of women, while 30% of children born in the breech presentation (P<0.05). Analyzing the data, we can assume that the intrauterine development occurred in the conditions of chronic hypoxia followed by exposure to intrapartum asphyxia. The average birth weight was 1900± 20,0, the growth - 44,4±1,2 sm. Period of early adaptation flowed for all the children in different ways. Apgar score was 4-6 points. In the first hours of life were marked lethargy and hypotonia, weak cry, spontaneous motor activity, inhibition of physiological reflexes. At 38.4% of the children was observed transient neurological symptoms (tremor when crying or small muscular hypotonia).
Dynamics of the vascular-platelet and coagulation parts of hemostasis in infants in the control group on the first day showed the following: kaolin-kefalinovoe time (KKV) reaches for the first day - 68,7±3,19 sec., plasma fibrinogen (PT) 3,4±0,3g/L, prothrombin time (PTT) 13,0±2,0 seconds, platelet-226,0±11,5x109; thrombin time 18,2±2,0 seconds, aggregation activity platelet 51,4±4,4 sek. At low birth weight infants, these figures were significantly different: kaolin-kefalin time (KKV) reaches for the first day - 98,9±2,29 sec., plasma fibrinogen (PT) 1,8±0,3g / L, prothrombin time (PTT) 18,0±2,0 seconds, platelet -134,0±11,5x109; thrombin time 23,2±2,0 seconds, aggregation activity platelet - 69,4±4,4sek (P<0,05). Especially characterized by low levels of fibrinogen, the functional activity of platelets, low platelet aggregation, which is a risk factor for intraventricular hemorrhage. It should be noted that, in preterm low birth weight infants hypocoagulation greatest shift was detected from the first days of life and maintained 10-14 days, whereas in healthy term infants hy-percoagulable first days gave way to anticoagulation, and the end of the 1st week in accordance with changes of adaptive mechanisms tended to stabilization of hemostasis. This is apparently helps to stabilize the hemodynamic and hemo-static processes.
In the study of cytokine spectrum of blood, we have found that an important informative indicator of the immune system of a newborn baby in the early period of adaptation is the
level of production of cord blood monocytes of TNF-a, IL-1^. The degree of increase of the concentration of IL-1^ and TNF-a serum of LBW newborns coincided with the severity of the child's condition. In newborn infants with low birth weight concentration of IL-1b in the peripheral blood serum had a tendency to increase since the 3rd day of life and were 0.450 ± 0,081pg/ml vs. 0,259±0,093 pg/ml (P<0,01) in the control group. In the following days the life of serum level of cytokine gradually decreased. The amount of TNF-a from the first days of life had significantly increased 82,3±1,2 pg/ml versus 8,3±1,9 pg/ml, respectively; (P<0,01) and persisted throughout the neonatal period.
Discussion. Increasing the concentration of IL-1^ and TNF-a in the blood may be an early diagnostic sign of the formation of multiple organ disorders and evidence of involvement of these immunocytokines in the pathogenesis of critical states of low birth weight infants. Probably, high serum level of TNF-a indicates the intensity of immunological reactions in the body of the child and plays a central role in the inflammatory response, tissue damage which may be a predictor, on the development of adjustment disorders in the early neonatal period. TNF-a increases the permeability of capillaries, vascular endothelial damage.
Analysis of the dynamics of certain hemostatic parameters testifies the variability of these parameters at different stages in the early neonatal period in low birth weight infants. At low birth weight infants the tension in the hemostatic system is observed from the first days after birth. A wide range of variation indicators vascular-platelet and coagulation level in the early neonatal period without severe clinical complications thrombohemorrhagic testifies a close connection with the processes of hemostasis homeostatic adaptation. At the same time the limits of fluctuations should not go beyond the physiological limits, which increase the risk of thrombotic and hemorrhagic complications. Together, these changes cause less stable hemostatic system, a much greater incidence of bleeding and the like inside the vascular blood clotting in this group of infants. Practically any abnormality is observed in premature infants, can be complicated by bleeding or DIC syndrome. This is due to the emergence of new factors affecting hemostasis. In particular, vascular endothelial dysfunction factors which are damaging hypoxia, ischemia, endotoxins and cytokines (TNF-a and IL-1^).
Conclusions
1. At low birth weight infants is observed variability hemostatic parameters at different stages of early neonatal period.
2. Pro-inflammatory cytokines lead to increased the tension all the hemostatic system and the endothelium dysfunction that underlie the formation of multiple organ disorders in the critical states of low birth weight infants.
References:
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