[The relationship between the development of post-stroke cognitive impairment and changes in the coagulation component of hemostasis]. / Svyaz' postinsul'tnykh kognitivnykh narushenii i izmenenii koagulyatsionnogo zvena gemostaza.

OBJECTIVE: To evaluate the relationship between the severity of post-stroke cognitive impairment (PSCI) and coagulation parameters assessed using the dynamic thrombophotometry. MATERIAL AND METHODS: Thirty-five patients with hemispheric ischemic stroke (IS) with moderate neurological deficit at admission were included. All patients underwent a comprehensive clinical and instrumental assessment according to the current guidelines. On days 10-14, the cognitive status of patients was assessed using the Montreal Cognitive Assessment (MoCA). Coagulation parameters were assessed using the dynamic thrombophotometry at admission, on 6-8th days and 13-15th days from the onset of the disease. A database of laboratory studies of 30 apparently healthy volunteers was used as a comparison group. RESULTS: Data analysis revealed that a number of spatial and temporal parameters were within the reference values, and there were no significant changes over time. Nevertheless, though the optical density of the fibrin clot (D) was within the reference values, it showed a steady increase from the admission by the end of the 1st week of the disease (p=0.007) and by 13-15th days (p=0.009). Correlation and multivariate linear regression, including baseline stroke symptom severity, showed significant associations (p<0.01 in all tests) between the higher optical density of the fibrin clot (D) on days 6-8 and 13-15 and lower MoCA score, confirming the negative effect of altered hemostatic parameters on cognitive function in IS patients. CONCLUSION: The increase of optical density of the fibrin clot (D) by 6-8th and 13-15th days is a potential prognostic biomarker for the early development of PSCI.

Hemostasis System in Patients with Schizophrenia and Schizophrenia Spectrum Disorders.

Hemostasis system in patients with schizophrenia and schizophrenia spectrum disorders was examined using "Fibrinodynamics" technology that allows evaluating the overal coagulation, fibrinolysis, and hemostasis potentials. All indices, except for the parameter characterizing the hemostasis balance, were statistically higher (p<0.0001) in patients than in healthy volunteers (control). In most patients, the hemostasis system remained balanced despite changes in individual coagulation and fibrinolysis parameters. The obtained results have a fundamental importance, expand the understanding of the pathogenesis of endogenous mental disorders, and are useful for the development of personalized approaches to the treatment of these patients.

[Piecewise linear regression model of hemostasis dynamics in donors and patients with schizophrenia]. / Kusochno-lineinaya regressionnaya model' dinamiki gemostaza u donorov i bol'nykh shizofreniei.

OBJECTIVE: This work is to develop and use a new approach to the analysis of differences between the velocity profiles of registered light signals in groups of patients with schizophrenia and healthy donors. MATERIAL AND METHODS: The present study involved 62 patients (all female) with schizophrenia or schizoaffective disorders in the acute period (observational study - 2016-2017). 44 patients were diagnosed with paranoid schizophrenia with an attack-progredient type of course (F20.01 according to ICD-10) or with a continuous type of course (F20.02). The fibrinodynamics test (FD) was performed on the T-2 thrombodynamics device (Hemacore LLC, Moscow), which makes it possible to monitor the processes of coagulation and fibrinolysis in the cuvette channels filled with fresh blood plasma. The result of the test are the brightness profiles of the clot. RESULTS: In the proposed approach, each profile is characterized by a vector of distances between it and other analyzed profiles. At that the distances between the profiles are calculated as the sum of the modules of differences at different points of the observation interval. This method makes it possible to overcome a certain loss of information that occurs when using a standard method based on the calculation of several parameters that characterize the analyzed velocity profiles. The method includes the construction of all kinds of statistically significant piecewise linear regression models that link the distances to two profiles. The velocity profiles corresponding to the points lying on opposite sides of the break point of such models have significantly different shapes. In practice, it turns out that for many piecewise linear regression models, the break points also significantly separate the velocity profiles for the compared groups of donors and patients with schizophrenia. Statistically significant deviations at the level p≤0.01 exist for 16.1% of 3143 statistically significant piecewise linear models. CONCLUSION: The developed method makes it possible to visually establish the relationship between the shape of the velocity profile and the presence of the disease.

[Cinnabarinic acid as a potential prognostic marker of schizophrenia]. / Tsinnabarinovaya kislota kak potentsial'nyi prognosticheskii marker shizofrenii.

OBJECTIVE: To develop a method for determining cinnabarinic acid (CA) and its immediate precursor 3-hydroxyanthranylic acid (3HAA) in blood plasma and to study their concentrations in patients with schizophrenia before and after treatment. MATERIAL AND METHODS: The study was carried out on a sample of 23 female patients with an attack-like progredient schizophrenia (F20.01). The levels of CA and 3HAA in blood plasma were measured using liquid chromatography with tandem mass spectrometry. RESULTS: We found an inverse statistically significant correlation of the sum of CA and 3HAA concentrations before treatment with the total PANSS score after treatment (R=-0.50; p<0.05). There was also an inverse correlation of the CA concentration of before treatment with the total PANSS score after treatment (R=-0.41, p=0.052), statistically significant at the trend level (0.05

[Evaluation of the levels of proinflammatory activity of monocytes in depressed patients with schizophrenia]. / Provospalitel'naya aktivnost' monotsitov u bol'nykh s depressivnymi sostoyaniyami v ramkakh shizofrenii.

OBJECTIVE: To evaluate the proinflammatory activity of monocytes (PAM) in depressed patients with schizophrenia by counting the proinflammatory monocyte number and to identify possible correlations between PAM and clinical indicators. MATERIAL AND METHODS: Sixty-eight women with depressive states in schizophrenia and 23 mentally and somatically healthy age- and sex-matched people were examined. The clinical condition of the patients was assessed by the total PANSS (PANSS_tot) and HDRS (HDRS_tot) scores. PAM was determined in the peripheral blood of patients and healthy controls by counting the number of large monocytes with a diameter of 12.5 to 15 microns on a cell counter and analyzer using the positive magnetic separation method to isolate a pure population of CD14 monocytes. RESULTS: Before treatment, the level of PAM significantly exceeded the corresponding value in controls (p<0.001) in half of the patients; after treatment, the level of PAM decreased to control values (p<0.001). Linear regression revealed in a subgroup of patients with an initially low PAM level a positive correlation between its value and HDRS tot (r=0.5, p<0.05) before treatment, that is, a low PAM level before treatment was accompanied by low-severity depressive disorders. The analysis of PAM level in the subgroups of patients responding and not responding to treatment revealed a decrease in the PAM value after treatment in the responding patients assessed by PANSS_tot (p<0.05) and in the responding patients assessed by HDRS_tot (p=0.06). Similar patterns were not detected in the subgroups of nonresponders. CONCLUSION: The correlations between the PAM level and the severity of depressive and other psychopathological disorders in patients with depressive states in schizophrenia may indicate the involvement of immune inflammation in the pathogenesis of this disease. The positive relationship between the initially low PAM level and the mild severity of depressive disorders can be used as a prognostic sign of patients' response to treatment.

[Paired and partial correlations of immune parameters of neuro-immuno-test and coagulation parameters of thrombodynamics test in children with children's autism]. / Parnye i chastnye korrelyatsionnye svyazi immunnykh pokazatelei neiroimmunotesta i koagulyatsionnykh parametrov trombodinamiki u bol'nykh detskim autizmom.

OBJECTIVE: To reveal paired and partial correlations of values of neuro-immuno-test and thrombodynamics test in children with childhood autism and schizophrenia in childhood in a state of exacerbation. MATERIAL AND METHODS: The study used a database of children with childhood autism, obtained by us in 2028-2019. The study included 46 patients with childhood autism (CA) aged 2 to 13 years: median age [Q1; Q3] - 5 years [4; 7], 10 girls (22%) and 36 boys (78%)). The thrombodynamics test (TD) was performed on a T-2 thrombodynamics analyzer according to the manufacturer's instructions. RESULTS: It was shown that there is a statistically significant positive correlation (R=0.369, p=0.018) between the acquired immunity parameter: the level of serum antibodies to myelin basic protein (BMP): abBMP parameter, and the main parameter of platelet hemostasis - the time of appearance of spontaneous clots (Tsp). It can be assumed that autoantibodies to BMP block the procoagulant effect of myelin basic protein and thus have an anticoagulant effect. However, this analysis did not take into account the possible effects of other parameter of the neuro-immuno-test and thrombodynamics test. Therefore, when studying the correlation of specific parameters of the neuro-immuno-test and thrombodynamics, it is necessary to take into account the possible modifying effect of other parameters of these tests. It was shown that after subtracting the influence on the main correlation (abBMP & Tsp) of individual thrombodynamic parameters (Vi, V and D), as well as their total influence, the partial correlations become statistically insignificant. This indicates that these TD parameters can, individually or in total, determine the revealed correlation between the levels of antibodies to the basic myelin protein (Basic Myelin Protein) and the time of the appearance of spontaneous clots. CONCLUSION: Thus, it was shown that the correlations between the studied parameters of the neuro-immuno-test and the indicators of the thrombodynamics test mutually depend on the other indicators of these tests. This confirms the hypothesis that the immune system and the hemostatic system are two different sides of a single supersystem.

[The decrease in procoagulant activity of blood during combined therapy with antidepressants and antipsychotics in patients with endogenous mental disorders]. / Snizhenie prokoagulyantnoi aktivnosti krovi u bol'nykh s endogennymi psikhicheskimi rasstroistvami pri kombinirovannoi terapii antidepressantami i antipsikhotikami.

OBJECTIVE: To compare the changes in thrombodynamics indices in two groups of patients with endogenous mental disorders before and after combined treatment with antipsychotics and antidepressants (AD + group) and those who did not receive antidepressants (AD-group). MATERIAL AND METHODS: The study included 110 patients, aged from 16 to 60 years (median age [Q1; Q3] 29 years [22; 35]), admitted for inpatient treatment at the clinic of Mental Health Research Center with the following mental disorders: schizophrenia with attack-like/attack-progressive/continuous type of course (F20.00-2), schizotypal disorder with affective fluctuations (F21.3-4), affective disorder (F 31.1-5; F 32.0-3; F 33.0-3). The thrombodynamics test (TD) was carried out on a T-2 thrombodynamics device according to the manufacturer's instructions (Hemacore LLC, Moscow, Russia). RESULTS: In patients with endogenous mental disorders after combined therapy with antidepressants and antipsychotics, a statistically significant decrease in the procoagulant activity of plasma and procoagulant spontaneous clots is observed, which indicates a decrease in the severity of systemic, immune inflammation. In patients with endogenous mental disorders after antipsychotic therapy without the addition of antidepressants, for most thrombodynamic parameters, there is no statistically significant decrease in procoagulant plasma activity and spontaneous clots formation. It indicates the persistence of acute systemic, immune inflammation in this group. CONCLUSION: The statistically significant positive change in plasma and platelet hemostasis may testify that combined treatment with antipsychotics and antidepressants in patients with endogenous mental disorders may be a biological, pathogenetic link that promotes augmentation (extended action) of antipsychotic therapy.

[A comparative analysis of two methods for assessing the proinflammatory activity of monocytes in patients with juvenile depression]. / Sravnitel'nyi analiz dvukh sposobov otsenki provospalitel'noi aktivnosti monotsitov pri depressii u bol'nykh yunosheskogo vozrasta.

OBJECTIVE: To show that the results of evaluation of monocyte pro-inflammatory activity (PA) in patients with juvenile depression and healthy donors, obtained using a new method developed by us for counting the relative number of large monocytes on a multifunctional counter and cell analyzer, are similar to the results obtained using a standard assessment of the level of proinflammatory CD14+/CD16+ - monocytes on a flow cytofluorimeter. MATERIAL AND METHODS: The PA of monocytes, isolated from the peripheral venous blood of 18 patients with juvenile depression and 12 mentally and somatically healthy age and gender-matched persons was evaluated in two ways: using the generally accepted method of determining the relative number of monocytes with the proinflammatory phenotype CD14+/CD16+ on a flow cytofluorometer FC-500 and by counting the relative number of large monocytes on a multifunctional counter and cell analyzer Multisizer MS-4. PA of monocytes in patients was studied by using both methods in different variants: in the general group and in the subgroups of patients with low and high levels of active monocytes. RESULTS: The levels of monocyte PA determined in patients using the two methods did not statistically differ from each other in all variants of the analysis (p=0.6). The equivalence of the obtained results was confirmed by the Chi-square test (r=0.77, p=0.05), as well as by the detection of a statistically significant positive correlation between the number of monocytes with the pro-inflammatory CD14+/CD16+ phenotype, on the one hand, and the relative number of large monocytes, on the other hand (Spearman r=0.75; p<0.05). At the same time, a comparative analysis of the level of monocyte PA in the general groups of patients and healthy controls revealed significantly higher values of this indicator in patients compared with healthy persons when evaluated by both methods (p<0.05). Definition of monocytes PA using the new method developed by us for counting the relative number of large monocytes on the analyzer and cell counter is more economical and easier to perform, since it does not require the use of expensive devices and reagents, as well as complex device settings and a high level of operator qualification, as in the common method, and is carried out only by two parameters: by counting the number of large monocytes with a diameter of 12.5 to 15 microns and the total number of monocytes with a diameter of 9 to 15 microns. CONCLUSION: The proposed method for assessing monocyte PA by counting the relative number of large monocytes on the cell counter and analyzer can be used to analyze the activity of monocytes for research purposes.

[Application of machine learning for predicting the outcome of treatment of patients with schizophrenia according to the indicators of «Thrombodynamics¼ test]. / Primenenie mashinnogo obucheniya dlya prognozirovaniya iskhoda lecheniya bol'nykh shizofreniei po pokazatelyam testa «Trombodinamika¼.

OBJECTIVE: To identify relationships between thrombodynamic values and the severity of the condition in patients with schizophrenia spectrum disorders (SSD) before and after treatment. MATERIAL AND METHODS: The study included 92 patients in an acute state of schizophrenia or schizotypal disorder, aged 16 to 57 years (median age [Q1; Q3] - 25 years). All patients received complex psychopharmacotherapy adequate to their psychopathological state. The PANSS was used to assess the severity of symptoms in patients. The coagulation parameters were determined by the thrombodynamics test, in which the growth of fibrin clots in platelet free plasma are observed from special activator. The patient population was divided into two groups with weak and strong response to treatment. Data analysis included machine learning (ML) techniques: logistic regression, random forests, decision trees, support vector machines with radial basis functions, statistically weighted syndromes, permutation method. RESULTS: An analysis using permutation method revealed statistically significant different thrombodynamics values between groups of patients with weak and strong responses. There are significant differences between thrombodynamics values: T1D, T2D, T2Tlag and DTlag, and values characterizing the severity of positive symptoms before and after treatment (T1PposTot, T2PposTot), severity of psychopathological symptoms before treatment (T1Ppsy1, T1Ppsy6, T1Ppsy13). All ML techniques showed the relationship between thrombodynamics values and response to treatment. The best statistical significance was for statistically weighted syndromes method. CONCLUSION: The combination of the results of different ML techniques at a high level of statistical significance identifies the thrombodynamic predictors of weak effect of treatment of SSD.

[A combined marker of catatonia severity including autoimmune and thrombodynamic parameters in patients with autism spectrum disorder]. / Kombinirovannyi marker tyazhesti katatonii, vklyuchayushchii immunnye i trombodinamicheskie pokazateli, u bol'nykh s rasstroistvami autisticheskogo spektra.

OBJECTIVE: To verify a working hypothesis that thrombodynamic parameters of hypercoagulation and neuro-immune test correlate with the severity of catatonia in patients with autism spectrum disorder (ASD), and the combination of these indicators can predict the severity of catatonia with high accuracy and precision. MATERIAL AND METHODS: Twenty-four patients with ASD (22 boys and 2 girls) with infantile psychosis in childhood autism (ICD-10 F84.02) were studied. The median age of the patients was 5,5 years. Neuro-immune and thrombodynamics tests were performed. RESULTS AND CONCLUSION: Thrombodynamic parameters of clot growth rates from the activator (V, Vi and Vst) are significantly higher than their normal values. The values of the time of spontaneous clots occurrence (Tsp) are significantly less than the lower limit values for the norm (30 min). It was also shown that the activity of leukocyte elastase (LE) and the functional activity of the α1 protein inhibitor (α1-PI) are significantly higher than their normal values. The values of the levels of autoantibodies to S100 protein (aabS100B) and the basic myelin protein (aabOBM) are within the normal range. The initial clot growth rate (Vi) and the time of spontaneous clots occurrence (Tsp) significantly correlate with the severity of catatonia: Spearman's R is 0,55 for Vi (p=0,009) and -0,61for Tsp (p=0,002). Among the parameters of the neuro-immuno-test, only aabS100B indicator significantly correlates with the severity of catatonia. To increase the informative significance and accuracy of the contribution of the studied correlates of thrombodynamics and the neuro-immuno-test to the assessment of the severity of catatonia in children with ASD, a multivariate linear regression analysis was performed to construct a linear equation for the relationship between the severity of catatonia and correlates of thrombodynamics and a neuro-immuno-test. The determination coefficient R2, which determines the informational significance of the regression model, is 0,63. The remaining 37% is explained by unaccounted and not yet known factors.

[Correlations between thrombodynamic parameters of coagulation and negative syndromes in patients with schizophrenia]. / Korrelyatsionnaya svyaz' trombodinamicheskikh pokazatelei koagulyatsii i negativnykh sindromov u bol'nykh shizofreniei.

OBJECTIVE: To identify a possible correlation between parameters of thrombodynamic coagulation and negative syndromes in patients with schizophrenia. MATERIAL AND METHODS: The study included 148 female inpatients, aged 16 to 57 years, with the following mental disorders: schizophrenia with attack-like/attack-progressive/continuous type of course (F20.00-2), schizotypal disorder with affective fluctuations (F21.3-4). The thrombodynamics test (TD) was carried out on a T-2 thrombodynamics recorder (Hemacore LLC, Moscow, Russia). RESULTS: A positive correlation was shown between the thrombodynamic parameters of clot growth rates (V, Vst, and Vi), clot size at the 30th minute (CS), and the total severity of negative syndromes (PANSS). There is a negative correlation between the time of spontaneous clots (Tsp) and the total severity of negative syndromes in patients. Positive correlations of V and Vst with scores on the fourth (Passive/apathetic social withdrawal), fifth (Difficulty in abstract thinking) and seventh (Stereotyped thinking) items of the PANSS negative subscale were revealed. There is a negative correlation between Tsp and the score on the 7th item, i.e. a shorter time for the appearance of spontaneous clots corresponds to a more pronounced Stereotyped thinking in patients. CONCLUSION: For the first time, correlations between thrombodynamic indicators of hypercoagulation and negative syndromes in patients with schizophrenia are identified, which emphasizes the need to normalize hemostasis to prevent further aggravation of these disorders.

[Reduction of plasma procoagulant activity in patients with schizophrenia during pharmacotherapy: thrombodynamic parameters of coagulation before and after treatment]. / Snizhenie prokoaguliantnoi aktivnosti plazmy krovi bol'nykh shizofreniei pri farmakoterapii: trombodinamicheskie pokazateli koaguliatsii do i posle lecheniia.

AIM: To detect plasma procoagulant activity in patients with schizophrenia at admission to the hospital in a state of exacerbation before (point 1) and after (point 2) pharmacotherapy and evaluate plasma and platelet hemostasis abnormalities. MATERIAL AND METHODS: The study included 80 women, aged from 16 to 57 years, median age 28 years, with schizophrenia with continuous, paroxysmal-progressive or paroxysmal course (F20.00, F20.01, F20.02 according to ICD-10). In 42 of 80 patients, depressive disorders in the structure of schizophrenia were observed. The thrombodynamic test (TD) was performed on T-2 Trombodynamis device according to the manufacturer's instructions (Hemacore LLC, Moscow, Russia). Blood for the TD test was taken in admission to the hospital (point 1) and on discharge (point 2). All patients received standard pharmacotherapy according to their condition. RESULTS: For the first time, it was established that in the whole group of patients (n=46) thrombodynamic indicators of the rate of growth of the clot: initial velocity (Vin), stationary velocity (Vst) and adjusted for spontaneous clots velocity (V) and the amount of clot for 30 minutes test TD (ClotSize, CS) were significantly higher compared to normal values. The mean time of occurrence of spontaneous thrombosis (Tsp) was significantly less than 30 min (p<0.0001), indicating rapid, spontaneous thrombosis. Other parameters of TD did not differ significantly from the norm. As a result of treatment, the initial growth rate of the clot from the activator (Vi) decreased from 58,5 µm/min to 54,5 µm/min; V speed from 37,4 µm/min to 33,5 µm/min; CS clot size from 1249 µm to 1219 µm; clot density - from 24 874 units up to 23 658 units. All these changes are significant. Such dynamics of plasma hemostasis clearly indicates a significant decrease in the coagulation activity of the blood plasma of patients as a result of treatment. An increase in the time of appearance of spontaneous clots after treatment (from 23.5 minutes to 30.5 minutes) indicates a decrease in the procoagulant activity of platelet microparticles after treatment, i.e. the reduction of platelet activation as a result of treatment. CONCLUSION: Our studies have shown for the first time that treatment of patients with antidepressants and antipsychotics reduces the generation of spontaneous clots. The treatment of patients with schizophrenia is accompanied by a decrease in the activity of plasma and platelet hemostasis. This is of great practical importance, since hypercoagulation of spontaneous clots in schizophrenic patients aggravates their chronic inflammatory disorders and affects their resistance to treatment.

[Platelets, hemostasis and mental disorders]. / Trombotsity, gemostaz i psikhicheckie rasstroistva.

Platelets are an easily accessible model for the study of biochemical mechanisms of mental diseases, including schizophrenia and depression. This literature review addresses a role of platelet activation in the pathogenesis of mental diseases. Platelet activation observed in patients with schizophrenia, depression and other mental illnesses is associated with the development of cardiovascular disease and an increased risk of thrombotic complications, which can be the main cause of morbidity and mortality in patients with mental disorders. A deeper understanding of the biochemical mechanisms of mental disorders will help in the study of clinical consequences of these disorders and in choosing the right therapeutic strategy for patients.

[Thrombodynamic parameters of hypercoagulation of blood in children with childhood autism and schizophrenia]. / Trombodinamicheskie pokazateli giperkoaguliatsii krovi u detei s detskim autizmom i detskoi shizofreniei.

AIM: To detect blood plasma coagulability in children with mental diseases using a thrombodynamics test. MATERIAL AND METHODS: The study included two groups of children. Group 1 included 11 patients with infantile psychosis in autism (F84.02) (4 girls and 7 boys). Group 2 included 8 patients with childhood schizophrenia (F20.8xx3) (4 girls and 14 boys). A test was performed with T-2 Thrombodynamics analyzer (LLC Hemacore, Moscow, Russia). RESULTS: Thrombodynamic parameters, such as initial, steady-state velocity and spontaneous clots adjusted velocity (Vi, Vst and V, µm/min, respectively) and clot size at 30 minute of thrombodynamics test (CS µm) were significantly increased in the total group of patients (n=29). The time of appearance of spontaneous clots (Tsp), the time of clot lag time (Tlag) and clot density (D) did not differ significantly from the normal values (p=0.98; p=0.27 and p=0.21, respectively). In the autism group (n=11), Vi, Vst and V were significantly higher than normal values, while CS, Tsp, Tlag and D did not differ from norm. In the schizophrenia group (n=18) V, Vst and CS, and Vi were significantly increased. Tsp, Tlag and D did not differ from normal values. Differences between the parameters of thrombodynamics in 1 and 2 groups were not statistical significant. CONCLUSION: It was shown for the first time that clotting (hypercoagulability) of the blood plasma in patients with autism and childhood schizophrenia was increased. This can cause thrombosis in small vessels of the brain. Early spontaneous clots appear in many patients that indicating the presence of systemic inflammation, possibly associated with an exacerbation of neuroinflammation. The thrombodynamics test allows detection of predisposition to hypercoagulability in the early stages when other methods are not sensitive enough.

[Thrombodynamic correlates of catatonia severity in children with autism]. / Trombodinamicheskie korreliaty tiazhesti katatonii u detei s autizmom.

AIM: To study a correlation between the values of thrombodynamics parameters of hypercoagulation measured by the thrombodynamics test and the severity of catatonia in children with infantile psychosis in childhood autism (F84.02). MATERIAL AND METHODS: Twenty-four patients (22 boys and 2 girls) aged from 3 to 13 years, were studied. The severity of catatonia was determined by BFCRS. A thrombodynamic test was performed in platelet-free plasma using the analyzer T-2 Thrombodynamics Device (Hemacore LLC, Russia). RESULTS: Thrombodynamic (TD) parameters of clot growth rates from the activator (V, Vi and Vst) were statistically significantly higher than normal values. Similar results were obtained for Clot Size at 30 min (CS, µm): Tlag and D values were within normal limits. The values of Time of appearance of spontaneous clots (Tsp min) were less than the lower limit values for the norm (30 min). Correlation analysis showed that the severity of catatonia is positively correlated with the initial clot growth rate (Vi) (p=0.009) and negatively with Tsp (p=0.002). With an increase in the time of appearance of spontaneous clots (due to a decrease in the procoagulant activity of platelet microparticles in the plasma of patients), the severity of catatonia in children with ASD decreases. CONCLUSION: The results suggest that normalizing plasma and platelet hemostasis is important for increasing the effectiveness of treatment of patients with ASD with catatonia.

[Thrombodynamic parameters of hypercoagulability in patients with affective disorder and schizophrenia in a state of exacerbation]. / Trombodinamicheskie pokazateli giperkoaguliatsii plazmy krovi u bol'nykh s affektivnym zabolevaniem i shizofreniei v stadii obostreniia.

AIM: To detect coagulability impairment of blood plasma in patients with schizophrenia or affective disease in a state of exacerbation using a thrombodynamics test. MATERIAL AND METHODS: The study included 46 women, 32 with attack-like/shift-like/or continuous schizophrenia (ICD-10: F20.00, F20.01, F20.02), 7 with schizotypal disorder (ICD-10: F21.3-21.4) and 7 with affective disorder (ICD-10: F32.00, F32.3). Thrombodynamics tests were performed on T-2 thrombodynamics analyzer ('Hemacore LLC', Moscow, Russia). RESULTS: For the first time, it was shown that in the patient population (n=46), the thrombodynamic parameters of the blood clot growth rate [initial velocity (Vi), steady-state velocity (Vst) and spontaneous clots adjusted velocity (V)] and clot size at 30 minute of thrombodynamics (Clot Size, CS) were significantly higher than normal values. The mean appearance of spontaneous clots (Tsp) was significantly lower than 30 minutes (p<0.0001) which indicated a rapid, spontaneous clots formation. The mean value of clot lag time (Tlag) and clot density (Density, D) did not differ significantly from normal values. The number of changed thrombodynamic parameters decreased in the following sequence: schizophrenia with different types of courses > schizotypal disorder>affective disorder. This is in good agreement with the fact that the course of affective disorders is more favorable than that in schizophrenia. CONCLUSION: The thrombodynamics test has a good potential for introduction into medicine to detect hypercoagulability and increased risks of thrombotic complications in patients, as well as to control for normalization of hemostasis with antiaggregant or anticoagulant drugs. Thrombodynamics makes it possible to identify a tendency to hypercoagulable states at an early stage, when other methods are still not sensitive enough. The study identified the hypercoagulability in patients with schizophrenia and affective disorders.

[Risk assessment of thrombotic events in patients with schizophrenia and schizoaffective disorder in the acute state: the 'fibrinodynamics' technology]. / Otsenka riska tromboticheskikh narushenii u bol'nykh shizofreniei i shizoaffektivnymi rasstroistvami v ostrom periode bolezni s ispol'zovaniem tekhnologii 'fibrinodinamika'.

AIM: To assess the risk of thrombotic events in patients with schizophrenia and schizoaffective disorder based on 'fibrinodynamics' technology. MATERIAL AND METHODS: A group of 76 women, including 38 with paranoid schizophrenia (F20.0), 18 with schizoaffective disorder (F25.1) in the acute stage, and 20 healthy controls, participated in the study. The technology includes the study of coagulation and fibrinolysis, Karmin author software, and calculation of peak time and hemostasis potential of spontaneous clots. Growth and lysis of fibrin clots were studied in plasma purified from platelets. All preanalytic procedures were conducted within 30 minutes after blood sampling. Blood serum was studied separately using the neuroimmunological test. Dynamic of brightness profiles of the clots was determined and a number of parameters (peak time and hemostasis potential of spontaneous clots) were calculated using the Karmin software. RESULTS: In patients with schizophrenia, the dynamic brightness profile of the clots has two peaks: the first peak is formed as a result of the growth and lysis of the clot initiated by the activator, the second peak is due to the growth and lysis of spontaneous clots in the volume of the measuring cuvette far from the activator. In healthy donors, the second peak under experimental conditions is absent. In the group of schizophrenic patients, a strong negative correlation is observed between the peak time of the second peak and the activity of leukocyte elastase (Spearman R = -0.75, p<0.0001), i.e. the greater the activity of elastase, the earlier the maximum of the second peak is formed and vice versa. In the control group, there is no such correlation. Evaluation of the potential of hemostasis of spontaneous clots showed that in 42% of schizophrenic patients this parameter is shifted above the norm, which indicates an increased risk of thrombosis of small brain arteries in these patients. CONCLUSION: The developed technology of 'fibrinodynamics' has a good potential for introduction into personalized medicine to identify increased risks of thrombosis of small cerebral vessels in patients with acute schizophrenia leading to the development of cognitive disorders and to control the normalization of hemostasis with antiplatelet or anticoagulant drugs.

[The cellular factors of innate immunity in nonpsychotic patients at high risk for schizophrenia]. / Kletochnye faktory estestvennogo immuniteta u bol'nykh s nepsikhoticheskimi psikhicheskimi rasstroistvami, otrazhayushchimi vysokii risk razvitiya shizofrenii.

AIM: Changes in the parameters of innate immunity in patients with schizophrenia are observed already in the first episode. The study was performed to find out whether these changes take place prior to disease manifestation, and what role do they play in the pathogenesis of schizophrenia. MATERIAL AND METHODS: Thirty-five male nonpsychotic patients at high risk of psychosis, aged between 17 to 23 years, were examined. Phagocyte activity (PA) of neutrophils in the blood serum was evaluated by the number of active neutrophils, i.e. phagocytic index (PhI), and phagocytic number (PhN), which was determined by counting latex particles absorbed with a single phagocytic cell. Cytotoxic activity of natural killer lymphocytes (NK CA) was evaluated by the number of cell targets K-562, which remained non-degraded after the contact with natural killer cells. The influence of monocytes on NKCA was determined as well. RESULTS AND CONCLUSION: Compared to controls, patients had the lower PhI level (p<0.001) which was compensated by the increase in PhN levels, and the lower NK CA level which was increased due to the influence of monocytes. Negative correlations between PhI and PhN (r= -0.83, p<0.01) and between the level of NKCA and PhI (r= -0.83, p<0.05) as well as the positive correlation between PhN and SOPS scores (r=0.69, p<0.01) were found. After treatment, there was the decreasein the severity of mental disorders (p<0.001). The level of PhAN was normalized in 61.9% of patients compared to 36.7% before treatment. After treatment, the proportion of patients with normal levels of NK CA was the same as before treatment (40 and 35%, respectively). The immune disturbances revealed in the study may play a role in the pathogenesis of the disease and have predictive value for schizophrenia.

Complement-Mediated Death of Ciliate Tetrahymena pyriformis Caused by Human Blood Serum.

Toxicity of human blood serum for ciliate Tetrahymena pyriformis is determined by the complement system. When ciliate are dying after being exposed to blood serum, cell membrane permeability for low-molecular-weight compounds significantly increases, probably due to pore formation. Serine protease inhibitors or exposure to physical factors inducing complement inactivation (e.g., heating up to 56°C) completely prevented ciliate death under the effect of human serum. Activation of serum complement upon interaction with Tetrahymena cells occurred by the classical or lectin pathway, while the contribution of the alternative activation pathway was negligible.

[The activity of complement system in children with autistic spectrum disorders]. / Aktivnost' sistemy komplementa u detei s rasstroistvami autisticheskogo spektra.

AIM: To evaluate the state of complement system (CS) activity in children with autistic spectrum disorders (ASD) and children with schizophrenia on the basis of development and implementation of a new method of CS determination. MATERIAL AND METHODS: A study included 249 patients, aged from 3 to 14 years. The control group consisted of 279 age-matched children. The authors developed a method for integral evaluation of CS activity based on the changes in the death of free swimming ciliata Tetrahymena pyriformis measured with the apparatus BioLat (Moscow, Russia). The integral CS activity (T50) was estimated as the time of death of 50% of ciliata in the blood serum (serum concentration was 5%). RESULTS AND CONCLUSION: A comparative analysis of CS activity showed statistical differences in median T50 values between patients and controls (p<0.005). Based on CS activity levels, three groups of patients were determined: 1) with the levels lower than the lowest value of the control group (n=112 (39%)); 2) higher than the highest level of the control group (n=103 (36%)); intermittent between low and high values of the control group (n=72 (25%)). Significant differences in T50 between the psychotic autism group and children schizophrenia group were identified (p<0.005). The CS activity was lower in patients with ASD compared to children with schizophrenia.