[Evaluation of hemostasis disorders using the thrombodynamic test in patients with chronic glomerulonephritis with nephrotic syndrome].

BACKGROUND: Nephrotic syndrome (NS) is accompanied by a risk of thrombotic complications due to hypercoagulability. Routine laboratory tests are not sensitive enough to detect these disorders, and therefore the use of integral coagulation tests, including a new thrombodynamic test (TT) in patients with NS, is of high relevance. AIM: Using a TT to determine hemostasis disorders in patients with chronic glomerulonephritis (CGN) with NS. MATERIALS AND METHODS: The study included 49 patients with CGN, mean age 37 years, of which 25 (51%) women and 24 (49%) men. Of all the examined patients, 20 (40.8%) of people had NS, 29 (59.2%) had no NS. The process of clot formation was assessed by TT. RESULTS: According to TT, 30% (6/20) of patients with NS and 13.7% (4/29) of patients without NS have hypercoagulation with changes in parameters that go beyond the reference values. In patients with NS, an increase in clot density (D), clot formation rate (V) and clot size (CS) was found, especially when albumin decreased below 25 g/l. Negative correlations were found between the levels of albumin, creatinine and clot density (D), which reflects the level of hyperfibrinogenemia, the rate of clot formation (V) and the integral index of coagulation (CS). The results indicate mainly the activation of the plasma hemostasis due to the internal coagulation pathway. However, the correlation of Tlag (delay time for the onset of clot formation after contact of blood plasma with the insert-activator) with serum cholesterol levels may also indicate activation of the extrinsic coagulation pathway. CONCLUSION: In CGN patients with NS, activation of the plasma hemostasis is noted, as evidenced by an increase in the rate of formation (V) and size of the clot (CS) after 30 minutes, as well as the density of the formed clot (D).

[Peculiarities of blood coagulation disorders in patients with COVID-19].

AIM: To study the relationship of hemostatic disorders with inflammation and estimate their role in the course and outcomes of COVID-19. MATERIALS AND METHODS: We examined 215 consecutive patients with moderate and severe forms of acute COVID-19. The patients were on anticoagulants and immunosuppressive drugs. Hemostasis was assessed using the thrombodynamics assay, thromboelastography, fibrinogen and D-dimer levels, prothrombin time, and soluble fibrin-monomer complexes (ethanol gelation test). The hemostatic parameters were correlated with hematological and biochemical tests, including markers of inflammation (C-reactive protein, interleukins 6 and 8), as well as with the disease severity and outcomes. RESULTS: Laboratory signs of coagulopathy were revealed in the vast majority of the cases. Despite the use of low-molecular-weight heparins in the prophylactic and therapeutic doses, coagulopathy in COVID-19 manifested predominantly as hypercoagulability that correlated directly with the systemic inflammation and metabolic changes due to liver and kidney dysfunction. A direct relationship was found between the grade of coagulopathy and the severity of COVID-19, including comorbidities and the mortality. The chronometric hypocoagulability observed in about 1/4 cases was associated with a high level of C-reactive protein, which may decelerate coagulation in vitro and thereby mask the true inflammatory thrombophilia. Persistent hyperfibrinogenemia and high D-dimer in the absence of consumption coagulopathy suggest the predominance of local and/or regional microthrombosis over disseminated intravascular coagulation. CONCLUSION: The results obtained substantiate the need for laboratory monitoring of hemostasis and active prophylaxis and treatment of thrombotic complications in COVID-19.

The laboratory control of anticoagulant thromboprophylaxis during the early postpartum period after cesarean delivery.

INTRODUCTION: The incidence of venous thromboembolism (VTE) after cesarean section is up to 0.6%, and the widespread use of cesarean section draws attention to this group. The dosage and duration of low-molecular-weight heparin (LMWH) prophylaxis after delivery is estimated by anamnestic risk-scales; however, the predictive potency for an individual patient's risk can be low. Laboratory hemostasis assays are expected to solve this problem. The aim of this study was to estimate the potency of tests to reflect the coagulation state of patients receiving LMWH in the early postpartum period. MATERIALS AND METHODS: We conducted an observational study on 97 women undergoing cesarean section. Standard coagulation tests (Fg, APTT, prothrombin, D-dimer), an anti-Xa assay, rotation thromboelastometry and thrombodynamics/thrombodynamics-4D were performed. Coagulation assay parameters were compared in groups formed in the presence or absence of LMWH to estimate the laboratory assays' sensitivity to anticoagulation. RESULTS: Coagulation assays revealed hypercoagulation after delivery and a tendency toward normalization of coagulation during early postpartum. The thromboprophylaxis results revealed a higher percentage of coagulation parameters within the normal range in the LMWH group. CONCLUSION: This research is potentially beneficial for the application of thrombodynamics and thrombodynamics-4D in monitoring coagulation among patients with high VTE risk who receive thromboprophylaxis with heparin.

Eculizumab effect on the hemostatic state in patients with paroxysmal nocturnal hemoglobinuria.

Paroxysmal nocturnal hemoglobinuria (PNH) is characterized by a hypercoagulable state associated with acute hemolysis. Eculizumab is used to reduce the intensity of intravascular hemolysis in PNH patients. The hemostatic status of three patients with PNH was assessed during eculizumab treatment by D-dimer assay and the global assays: thromboelastography (TEG), thrombin generation test (TGТ), and thrombodynamics (TD). In the state of hemolytic crisis before the therapy D-dimer concentration was increased in two patients accompanied by hypercoagulation changes in TEG parameter angle (α). TD parameter the clot growth velocity (V) revealed hypercoagulability while TGT parameter ETP was within the normal range in all patients. The lactate dehydrogenase (LDH) activity decreased during the 8months of eculizumab therapy. The physical health was improved, the frequency of hemolytic crisis decreased. Patients periodically exhibited hypercoagulable state: the mean values α=38±11° (with normal range 20-40°), ETP=1311±442nM·min (with normal range 800-1560nM·min), V=31±4µm/min (with normal range 20-29µm/min). During the eculizumab therapy two patients had the repeated clinical manifestation of acute hemolytic crisis, the parameters of the global tests were increased compared to the previous measurement. The global hemostasis tests TEG, TGT and TD revealed hypercoagulability in patients with PNH during eculizumab therapy.

Thrombodynamics as a tool for monitoring hemostatic disorders in patients with chronic glomerulonephritis complicated by nephrotic syndrome.

Nephrotic syndrome (NS) is associated with a high risk for venous and arterial thrombosis due to hypercoagulability. Integral tests designed to assess hemostasis can become an alternative for measuring hypercoagulability in patients with NS. STUDY OBJECTIVE: To assess hemostatic disorders in CGN patients complicated by NS using the thrombodynamics test. MATERIALS AND METHODS: The study included 60 adult patients with chronic glomerulonephritis (CGN), mean age 37 years, 31 (52%) women, and 29 (48%) men. Among all patients, 53 % of patients had NS, 47 % had no sign of NS. Hemostasis was assessed using the thrombodynamics test. The results were compared with biochemical parameters, which are usually associated with NS and renal dysfunction. RESULTS: According to the thrombodynamics test, CGN patients with NS demonstrated a tendency to hypercoagulability: increased rates of V (rate of clot growth), increased D (clot density), and increased CS (clot size) after 30 minutes. A positive correlation of these parameters with the serum albumin, creatinine levels, and glomerular filtration rate (GFR) indicates the influence of severe NS and renal dysfunction on the hemostasis activation in CGN patients with NS. CONCLUSION: According to the thrombodynamics test, CGN patients with NS demonstrate increased rates of clot formation, increased clot size after 30 minutes, and increased clot density due to secondary hemostasis activation. These changes positively correlate with the severity of hypoalbuminemia, hypercholesterolemia, and renal dysfunction in NS patients.

Correction of Anticoagulant Therapy in Patients with Severe COVID-19 Virus Infection Using a Thrombodynamics Coagulation Assay.

BACKGROUND: The average frequency of thrombosis in patients with COVID-19 is still high despite low molecular weight heparin (LMWH) prophylactic. Global hemostasis assays, particularly thrombodynamics (TD), known to be sensitive to both hypercoagulation and heparin effects, could potentially be useful for individual management of anticoagulant therapy. METHODS: A total of 74 patients with lung involvement >50% were randomized into two groups: Group A (44 patients) received weight-based dosing of LMWH, and Group B (30 patients) received the first LMWH dose by a weight-based dosing protocol and then received an adjusted dose based on TD daily results. The endpoints of the study were thrombosis and bleeding as well as discharge or death of the patient. RESULTS: The incidence of thrombosis was 3 times lower in Group B under TD control compared to Group A without TD control: 7% versus 23 respectively (p = .05). The relative risk of thrombosis if the average clot growth rate V in TD exceeded the threshold value of 25 µm/min was 14.3 (p = .0005, 95% confidence interval 3.2-63.7). There were no clinically significant bleeding episodes in Group B while there were 7% in unregulated Group A. Mortality in Group B under TD control was lower than that in Group A without control: 27% versus 36%, respectively (p = .13). CONCLUSIONS: The dosing LMWH under thrombodynamics control in severe patients with COVID-19 allows for a significant reduction in thrombotic complications. Long-term hypercoagulation revealed by thrombodynamics (3 and more days) is a strong predictor of thrombosis (AUC = 0.83).

[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.

[The possibility of using integral indicators of thrombodynamics for the safety of rehabilitation treatment after a stroke]. / Vozmozhnost' ispol'zovaniya integral'nykh pokazatelei trombodinamiki dlya bezopasnosti reabilitatsionnogo lecheniya posle insul'ta.

OBJECTIVE: To assess the possibility of using the integral indicators of thrombodynamics to improve the safety of rehabilitation measures in patients in the recovery period of stroke. MATERIAL AND METHODS: A prospective study included 52 patients in the recovery period of stroke. To compare the effect of the intensity of physical activity on the change in the integral indicators of thrombodynamics in accordance with the objectives of the study, the patients were randomized into two groups. In the first group, patients received treatment, including physiotherapy, stabilometric trainings, neuropsychological tasks. Patients of the second group received complex treatment, including more intense physical activity with the use of cyclic exercises, biomechanotherapy. To assess the state of hemostasis, an integral thrombodynamics test was used, and the numerical parameters of the spatial dynamics of the growth of a fibrin clot were calculated. RESULTS: The state of compensated hypercoagulability was revealed in the majority of patients before the start of medical rehabilitation, despite taking antithrombotic therapy, which was evidence of the ineffectiveness of the therapy. At the same time, it was noted that it was its action, probably during the ongoing program of physical rehabilitation, that ensured the stability of the integral indicators of thrombodynamics and the absence of clinically significant unwanted thromboembolic complications. As a result of the analysis of the data in dynamics before and after treatment, a direct relationship was traced between the intensity of physical activity and the tendency to disturb the hemostatic balance. CONCLUSION: The intensity of physical activity during treatment undoubtedly influenced the state of hemostasis. The expediency of monitoring the dynamics of coagulation activity in patients in the recovery period of stroke has been demonstrated.

[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.

Utilization of the Caprini score in conjunction with thrombodynamic testing reduces the number of unpredicted postoperative venous thromboembolism events in patients with colorectal cancer.

BACKGROUND: The thrombodynamic test (TD) is a novel global test of hemostasis that allows to study the spatial-temporal characteristics of a clot formation in real time under conditions close to natural ones and demonstrates high sensitivity to detect the state of hypercoagulation. The main paraments of the test are the velocity of clot growth, clot's size, and clot density. The objective of this study was to compare the classic Caprini 2005 score and its modified version in association with the results of TD. The goal is to predict postoperative venous thromboembolism (VTE) in surgical patients undergoing surgery for colorectal cancer. METHODS: This was a prospective observational clinical study involving 80 patients (33 men and 47 women; mean age, 73.9 ± 7.2 years) who underwent major (79 cases) or minor (1 case) surgery for colorectal cancer. Patients were at high risk for postoperative VTE (ie, a mean Caprini score of 9.9 ± 2.0) and received combined prophylaxis (ie, antiembolic compression stockings and enoxaparin 40 mg once daily) until discharge. Enoxaparin was administered at a fixed time of blood sampling for the TD test. Duplex ultrasound scan was performed to detect postoperative vein thrombosis before and 5 to 7 days after surgery. RESULTS: Postoperative vein thrombosis was found in 21 of 80 patients (26.3%; 95% confidence interval, 17.9%-36.8%). Regression analysis and receiver operating characteristic (ROC) curve showed that Caprini scores significantly predicted VTE (P < .0001; area under the curve [AUC] = 0.839 ± 0.045). Analysis of ROC curve coordinates showed that a cutoff point of 11 scores had a sensitivity of 76.2% and a specificity of 74.6%. The results of the TD test showed significant hypercoagulation despite enoxaparin administration in patients with VTE. Regression analysis and ROC curves demonstrated that the following TD parameters had the greatest predictability for postoperative DVT: initial velocity of clot growth (Vin) and clot size (CS) measured at 12 hours after enoxaparin administration (AUC, 0.697 ± 0.063 and AUC, 0.790 ± 0.059, respectively), as well as Vin and CS measured 24 hours after the enoxaparin injection (S = 0.847 ± 0.059 and S = 0.803 ± 0.069, respectively). The cutoff points for VTE prediction at 12 and 24 hours seemed to be a Vin of greater than 62.5 and greater than 64.5 µm/minute (normal range, 35-56 µm/minute) as well as a CS of greater than 1351.5 and greater than 1333.5 µm (normal range, 800-1200 µm), respectively. Identified thresholds for TD parameters have been integrated into Caprini scores under the item "other congenital or acquired thrombophilia." The total Caprini scores were recalculated in patients where one or all TD parameters had exceeded the cutoff followed by reanalysis of the ROC curves. The best predictability was found for Caprini scores considering the elevation of all four TD parameters (AUC, 0.924 ± 0.029) with increased cutoff to a score of 12 with a sensitivity of 85.7% and a specificity of 81.4%. The use of cutoffs for the original and modified scores could be used to calculate the number of patients that were under cutoff but developed with VTE: 10.2% and 5.9%, respectively. CONCLUSIONS: Integrating TD parameters into the Caprini score increases the ability to predict postoperative VTE.

[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.

[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.

Hyper-coagulability in obese patients accurately identified by combinations of global coagulation assay parameters.

BACKGROUND: Routine laboratory methods are insensitive to hyper-coagulation, which may be detected by global hemostasis tests. Calibrated Automated Thrombogram (CAT) is a gold standard method to measure thrombin generation and coagulation potential. Thrombodynamics (TD) is a new global assay that monitors the spatio-temporal propagation of blood coagulation, separating initiation from amplification/propagation phases of coagulation and visualizing fibrin clot formation. AIM: We investigated whether CAT and/or TD can identify hyper- and hypo-coagulable states in patients with well-characterized phenotypes and which parameters could be used as potential predictors of thrombotic risk. METHODS: Blood was collected from: (1) forty healthy volunteers; (2) twelve obese patients scheduled for bariatric surgery (BMI ≥ 35 kg/m2); (3) nine patients under therapy with vitamin K-antagonists (median INR 2.7); (4) eight patients treated with low molecular weight heparins (anti-Xa activity between 0.5 and 0.7 U anti-Xa/ml); (5) ten patients with hemophilia A or B. Tissue factor induced thrombin generation was measured with CAT. Propagation of thrombin generation and clot growth from a tissue factor coated surface were monitored with TD. RESULTS: Thrombin generation and fibrin clot formation parameters were significantly higher in obese patients compared to healthy volunteers and anticoagulated or hemophilic patients. ROC analysis of combined CAT or CAT/TD parameters (integrating thrombin generation and fibrin clot formation) demonstrated an excellent accuracy in detecting hyper-coagulability. CONCLUSION: Combinations of CAT assay parameters and of parameters of thrombin generation burst with final fibrin clot properties allow recognizing accurately hyper-coagulable plasma and may represent predictive markers for thrombotic events.

[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.

[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.

C1-esterase inhibitor enhances thrombin generation and spatial fibrin clot propagation in the presence of thrombomodulin.

Package inserts for C1-esterase inhibitor (C1INH) products include warnings for an elevated risk of possible thrombosis in certain individuals, referring to thromboembolic events (TEEs) that were reported to occur after C1INH infusions. However, the mechanism(s) that could explain possible development of TEEs due to C1INH remains unknown. In this work, we evaluated plausible impact of C1INH on the protein C (PC) anticoagulant system. We performed thrombin generation (TG) assays (TGA) and analyzed spatial fibrin clot propagation using thrombodynamics in plasma of individual donors after the addition of thrombomodulin (TM) and C1INH. The addition of C1INH was consistent with the plasma concentrations resulting from doses currently approved for the HAE treatment up to ones consistent with off-label use in patients with risk of inflammation. 16 IU/ml of C1INH significantly enhanced thrombin peak (TP) generation in the presence of 12 and 15 nM TM. TG enhancement was observed by the addition of C1INH to make concentrations equal to 2 and 4 IU/ml in some donor plasmas. C1INH addition in the presence of TM enhanced the stop time of spatial clot growth in Thrombodynamics assay. A chromogenic activity assay demonstrated that C1INH inhibited PC activation by thrombin in the presence of TM. Substitution of TM with APC in TGA attenuated the TP enhancing effect of C1INH. The collective results of the present study suggest a concentration dependent C1INH interaction with the PC system. This study introduces a plausible TM-dependent mechanism, that may explain reported TEEs via suppressed production of APC in the presence of C1INH.

The hemostasis system in children with hereditary spherocytosis.

INTRODUCTION: Patients with hereditary spherocytosis (HS) are characterized by having an increased risk for thrombosis. An early manifestation of thrombotic complications can occur even in childhood, especially after surgery. Hypercoagulability can be associated with hemolytic crises. AIM: The aim of this study was to investigate the hemostatic state in children with HS using global hemostasis assays. METHODS: The hemostatic status of 62 children (38 boys and 24 girls; age range: 0.5 to 17 years) with HS during and without hemolytic crisis was assessed using clotting times (APTT, TT, and PR), fibrinogen and D-dimer levels, and global hemostasis, thromboelastography (TEG) and thrombodynamics (TD) assays. One hundred and two healthy children undergoing annual medical examination were enrolled as a control group. RESULTS: TEG and TD parameters were increased in the children with HS compared to the control group (60 ±â€¯5 mm vs. 53 ±â€¯4 mm, p < 0.05 for TEG maximum amplitude; 28 ±â€¯3 µm/min vs. 24 ±â€¯2 µm/min, p < 0.05 for TD clot growth rate), while APTT, TT and PR were not significantly different between the two groups. Patients with HS were divided into 2 groups: those during hemolytic crisis (28 patients) and those without hemolytic crisis (34 patients). TEG and TD parameters were increased in those during hemolytic crisis compared to the steady state HS group (62 ±â€¯5 mm vs. 57 ±â€¯4 mm, p < 0.05 for TEG maximum amplitude; 31 ±â€¯4 µm/min vs. 26 ±â€¯3 µm/min, p < 0.05 for TD clot growth rate). The D-dimer levels were increased in 4 HS patients, for whom the activation of blood clotting was noted. Fibrinogen levels were decreased in patients with HS compared to the control group (2.1 ±â€¯0.4 mg/ml vs. 2.6 ±â€¯0.4 mg/ml, p < 0.05). Other tests were within the reference ranges for both groups. CONCLUSIONS: The global hemostasis tests TEG and TD revealed hypercoagulability in patients with HS. More dramatic changes were observed in patients experiencing a hemolytic crisis.

Relationship Between Haemostasis Parameters and Anxiety Under Examination Stress: A Pilot Study.

This work aims to clarify how blood coagulation parameters reflect mild stress response in males and females. Healthy student volunteers of both sexes were used in this pilot study. A new global sensitive assay of haemostasis, spatial thrombodynamics, along with conventional coagulometry approach were used to evaluate of blood coagulation parameters. Psychodiagnostics scales (according to Spielberger and Taylor) are employed to evaluate anxiety as stress-induced response. We have selected exam stress, which despite being a mild stressor may nevertheless cause somatic disorders. We provide the first evidence of a statistically significant increase in initial clot growth velocity in women, but not men, in response to exam stress. The exam situation produces higher situational anxiety in female volunteers, and so they express remarkable stress-induced haemostatic responses, including plasma- and platelet-based changes. In contrast, male volunteers do not express pronounced stress-induced changes in haemostasis, and only display a decrease in plateletcrit value and an increase in prothrombin time. Mild form of stress (exam) induces changes in some blood coagulation parameters. A statistically significant remarkable increase in Vinit value and some other plasma- and platelet-based parameters has been seen in female students (but not male ones) under exam stress.