Вопросы гематологии/онкологии и иммунопатологии в педиатрии № Фибринолиз -важный биохимический процесс, отвечающий за разрушение фибриновых сгуст-ков, образующихся в результате работы системы свертывания. Сбои в работе системы фибри-нолиза могут приводить к состояниям, угрожающим жизни, -тромбозам и неконтролируемым кровотечениям. Наблюдается стремительный прогресс в понимании молекулярных механизмов работы системы фибринолиза, детально описаны все основные участники и реакции процес-са, тем не менее вопросы регуляции и оценки состояния системы фибринолиза изучены слабо. В данном обзоре представлен анализ накопленной информации о работе системы фибриноли-за и сопутствующей патологии. Подробно рассмотрены методы оценки и диагностики состояния системы фибринолиза. Fibrinolysis is an important biochemical process responsible for the dissolution of fibrin clots, which appear during the blood coagulation process. Disorders in fibrinolysis system may result in life-threatening conditions like thrombosis and bleedings. At this time, we know a lot about the molecular mechanism of fibrinolysis, all reactions are described in details, and yet its regulation and evaluation of fibrinolysis state are still unclear. In this review we analyze the information about how fibrinolysis functions and what disorders of this system can be met. We describe in details the methods used to evaluate the state of fibrinolysis system. Key words: fibrinolysis, blood coagulation, plasmin, evaluation of fibrinolysis state.ри повреждении сосуда происходит активация системы свертывания, цель которой -закрыть место повреждения, защищая организм от кро-вопотери и позволяя восстановить целостность сосу-дистого русла. При этом запускается множество процессов: одни отвечают за формирование тромбо-цитарного агрегата, другие обеспечивают образова-ние фибринового сгустка, третьи вызывают растворе-ние тромба. Отдельные белки могут принимать участи во всех процессах, обеспечивая взаимную регуля-цию различных этапов свертывания. В данном обзоре мы остановимся на функционировании и регуляции финального этапа существования тромба -фибри-нолизе.Нарушения в системе фибринолиза могут быть связаны с увеличением риска развития венозного тромбоза [1], но не во всех работах такая закономер-ность была обнаружена [2]. В ряде случаев, таких как инфаркт миокарда, тромбоз глубоких вен, легочная эмболия, инсульт, возникает необходимость экстрен-ного удаления тромба, препятствующего кровотоку. Для этого фибринолитическую систему организ-ма приводят в гиперактивное состояние при помощи таких препаратов, как тканевый активатор плазми-ногена, стрептокиназа [3] или урокиназный актива-тор плазминогена [4]. Фибринолитическая терапия показала свою эффективность при лечении пациен-тов с инсультом, однако такая терапия сопровожда-

BACKGROUND: Preterm newborns are at thrombohemorrhagic risk during the early neonatal period. Taking into account the lack of informative tools for the laboratory diagnosis of hemostasis disorders in newborns, our goal was to determine the baseline values of thrombodynamics and platelet functional activity in healthy term and moderately preterm newborns during the early neonatal period future potential clinical use of these tests. METHODS: Coagulation was assessed using an integral assay of thrombodynamics and standard coagulation assays, and platelet functional activity was estimated by flow cytometry. RESULTS: Hypercoagulation of newborns, represented by a significantly higher clot growth velocity and the presence of spontaneous clots in the thrombodynamics, was combined with platelet hypoactivity. Granule release, phosphatidylserine exposure, and the ability to change shape upon activation were decreased in the platelets of moderately preterm newborns. The platelet function remained at the same level over the first four days of life, whereas the hypercoagulation became less pronounced. CONCLUSIONS: The hemostasis of newborns is characterized by hypercoagulation combined with reduced platelet functional activity. Moderately preterm and term newborns do not differ in the parameters of coagulation, while some of the functional responses of platelets are lower in moderately preterm newborns than in term.

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Blood coagulation is a delicately regulated space-and time-dependent process that leads to the formation of fibrin clots preventing blood loss upon vascular injury. The sensitivity of the coagulation network was previously investigated without accounting for transport processes. To investigate its sensitivity to coagulation factor deficiencies in a spatial reactiondiffusion system, we combined an in vitro experimental design with a computational systems biology model. Clot formation in platelet-free plasma supplemented with phospholipids was activated with identical amounts of tissue factor (TF) either homogeneously distributed (concentration 5 pM, homogeneous model) or immobilized on the surface (surface density 100 pmole/m 2 , spatially heterogeneous model). Fibrin clot growth and thrombin concentration dynamic in space were observed using video microscopy in plasma of healthy donors or patients with deficiencies in factors (F) II, FV, FVII, FVIII, FIX, FX, or FXI. In the spatially heterogeneous model, near-activator thrombin generation was decreased in FV-, FVII-, and FX-deficient plasma. In the homogeneous model, clotting was not registered in these samples. The simulation and experiment data showed that the coagulation threshold depended on the TF concentration. Our data indicate that the velocity of spatial clot propagation correlates linearly with the concentration of thrombin at the clot wave front but not with the overall thrombin wave amplitude. Spatial clot growth in normal plasma at early stages was neither reaction nor diffusion limited but became diffusion limited later. In contrast, clot growth was always diffusion limited in FV-, FVII-, and FX-deficient plasma and reaction limited in FVIII-, FIX-, and FXI-deficient plasma. We conclude that robustness of the spatially heterogeneous coagulation system was achieved because of the combination of 1) a local high TF surface density that overcomes activation thresholds, 2) diffusion control being shared between different active factors, and 3) an early saturated stimulus-response dependence of fibrin clot formation by thrombin.