Use of Thrombodynamics for revealing the participation of platelet, erythrocyte, endothelial, and monocyte microparticles in coagulation activation and propagation.

Background And Objective: For many pathological states, microparticles are supposed to be one of the causes of hypercoagulation. Although there are some indirect data about microparticles participation in coagulation activation and propagation, the integral hemostasis test Thrombodynamics allows to measure micropaticles participation in these two coagulation phases directly. Demonstrates microparticles participation in coagulation activation by influence on the appearance of coagulation centres in the plasma volume and the rate of clot growth from the surface with immobilized tissue factor.

Computer Design of Low-Molecular-Weight Inhibitors of Coagulation Factors.

The review discusses main approaches to searching for new low-molecular-weight inhibitors of coagulation factors IIa, Xa, IXa, and XIa and the results of such studies conducted from 2015 to 2018. For each of these factors, several inhibitors with IC < 10 nM have been found, some of which are now tested in clinical trials. However, none of the identified inhibitors meets the requirements for an "ideal" anticoagulant, so further studies are required.

New factor Xa inhibitors based on 1,2,3,4-tetrahydroquinoline developed by molecular modelling.

Factor Xa is a serine protease representing a crucial element in the coagulation process and an attractive target for anticoagulant therapy. At the present time there are several chemical classes of factor Xa inhibitors with proven activity. Furthermore, three factor Xa inhibitors have been approved for the medical use to date.

Moderate plasma dilution using artificial plasma expanders shifts the haemostatic balance to hypercoagulation.

Artificial plasma expanders (PEs) are widely used in modern transfusion medicine. PEs do not contain components of the coagulation system, so their infusion in large volumes causes haemodilution and affects haemostasis. However, the existing information on this effect is contradictory.

The modification of the thrombin generation test for the clinical assessment of dabigatran etexilate efficiency.

A new oral anticoagulant, dabigatran etexilate (DE, a prodrug of direct thrombin inhibitor (DTI) dabigatran), has been used clinically to prevent thrombosis. The assessment of dabigatran efficiency is necessary in some clinical cases, such as renal insufficiency, risk of bleeding, and drug interactions. However, a specific thrombin generation test (TGT) that is one of the most informative and sensitive to anticoagulant therapy (calibrated automated thrombinography (САТ)) shows a paradoxical increase of test parameters, such as endogenous thrombin potential (ETP) and peak thrombin, in patients receiving DE.

[Regulation of Membrane-Dependent Reactions of Blood Coagulation].

All major coagulation reactions do not occurs in blood plasma itself, these processes are actually two-dimensional reactions localized to thephospholipid membranes. Almost all blood cells, lipoproteins, and microparticles provide assembly of protein complexes. A central role among them are played by platelets and platelet-derived microparticles.

Global assays of hemostasis in the diagnostics of hypercoagulation and evaluation of thrombosis risk.

Thrombosis is a deadly malfunctioning of the hemostatic system occurring in numerous conditions and states, from surgery and pregnancy to cancer, sepsis and infarction. Despite availability of antithrombotic agents and vast clinical experience justifying their use, thrombosis is still responsible for a lion's share of mortality and morbidity in the modern world. One of the key reasons behind this is notorious insensitivity of traditional coagulation assays to hypercoagulation and their inability to evaluate thrombotic risks; specific molecular markers are more successful but suffer from numerous disadvantages.

[Influence of temperature on spatial fibrin clot formation process in thrombodynamics].

In this study we have investigated the process of spatial fibrin clot formation in non-steered platelet-free plasma at the temperatures from 20°C to 43°C using thrombodynamics - the novel in vitro hemostasis assay, which imitates the process of hemostatic clot growth in vivo. During data processing the following parameters were calculated: initial (V i ) and stationary (V st ) rates of clot growth which characterize initiation and propagation phases of clotting process, and clot size on the 30 th minute. The temperature dependence of extrinsic and intrinsic tenase activities, which determine values of the initial and stationary clot growth rates, respectively, have been also measured.

Circulating contact-pathway-activating microparticles together with factors IXa and XIa induce spontaneous clotting in plasma of hematology and cardiologic patients.

Background And Objective: Using an in vitro experimental model of immobilized tissue factor-initiated clot growth in platelet-free plasma (thrombodynamics), we observed formation of activator-independent isolated spontaneous clots (SC) throughout the plasma volume in patients with cardiac infarction, acute leukemia, hemolytic anemia, and some other disorders. The aim of this work was to characterize this phenomenon and to identify the mechanisms of SC formation.

Methods And Results: Tissue factor inhibitor (VIIai) prevented SC in only 2 out of 23 patient plasma samples.

Task-oriented modular decomposition of biological networks: trigger mechanism in blood coagulation.

Analysis of complex time-dependent biological networks is an important challenge in the current postgenomic era. We propose a middle-out approach for decomposition and analysis of complex time-dependent biological networks based on: 1), creation of a detailed mechanism-driven mathematical model of the network; 2), network response decomposition into several physiologically relevant subtasks; and 3), subsequent decomposition of the model, with the help of task-oriented necessity and sensitivity analysis into several modules that each control a single specific subtask, which is followed by further simplification employing temporal hierarchy reduction. The technique is tested and illustrated by studying blood coagulation.

[Contractile properties of fibers and cytoskeletal proteins of gerbil's hindlimb muscles after space flight].

The work had the goal to compare the microgravity effects on gerbil's muscles-antagonists, m. soleus and m. tibialis anterior.