Spontaneous Clotting Research Articles

Spontaneous Clots in Body Fluids: Can They Cell Block?

Spontaneous Clots in Body Fluids: Can They Cell Block?

Comparison of standard and global hemostasis assays in cord and peripheral blood of newborns.

Umbilical cord blood is used for the testing of various parameters in newborns. However, data on its applicability for hemostasis assays is insufficient. To evaluate whether umbilical cord blood can be used for standard tests, thromboelastometry and thrombodynamics for preterm and term newborns. 187 newborns were included in the study. Blood was taken from the umbilical cord and by venipuncture of the newborn. Clotting times, fibrinogen, D-dimer, thromboelastometry and thrombodynamics were measured. Clotting times and fibrinogen indicated a hypocoagulable shift, while thromboelastometry and thrombodynamics showed a hypercoagulable shift in hemostasis in umbilical cord blood compared to newborn blood. D-dimer indicated an enhanced process of thrombus lysis in newborn blood compared to cord blood. Collecting blood into a tube with the addition of a contact pathway inhibitor did not significantly change the global assay parameters in either umbilical cord blood or newborn blood. In the thrombodynamics assay, spontaneous clotting was detected but suppressed by the addition of a tissue factor inhibitor. Hemostasis in cord and newborn blood differs for both global and standard tests. Hypercoagulability in newborns registered with the global assay thrombodynamics is associated with the presence of tissue factor in the blood. 1. We found a hypercoagulation shift in newborns compared with the adult references, possibly due to the presence of tissue factor in blood. 2. Blood coagulation is enhanced in cord blood compared with blood sampled from the vein of a newborn according to thromboelastometry and thrombodynamics assays. 3. Clotting times and fibrinogen concentrations in cord blood differ from these parameters in newborn blood. 4. Studying of the (patho)physiological features of hemostasis in newborns should consider differences in cord blood and vein sampled blood.

Pro‑coagulant Considerations in Patients with Arterial Hypertension and Multifocal Atherosclerosis

The aim of the work to determine the features of hemostasis and blood rheology in patients with arterial hypertension (HTN) and multifocal atherosclerosis (MFA).Materials and methods. The study enrolled male and female patients aged from 40 to 70 years, including 59 patients with controlled stage I–II hypertension and multifocal vascular lesions (Group 1) and 42 patients with controlled stage III hypertension, who have suffered an ischemic stroke and have multifocal vascular lesions (Group 2). A test using the Thrombodynamics analyser system T-2 (GemaKor, LLC, Moscow, Russia) was performed to detect the impairment of hemostasis.Results. Patients with HTN and MFA have an impaired coagulation hemostasis system (an increase in the initial and stationary clot growth rate and the size of the clot, as well as the presence of spontaneous clots), which leads to a high residual risk of cerebral complications, despite BP lowering to target figures and control of lipid profile.Discussion. Elevated blood pressure in patients with MFA leads to endothelial dysfunction, which is accompanied by activation of coagulation and fibrinolysis pathways. These changes lead to a violation of microcirculatory hemostasis in the brain, the development and progression of cerebral ischemia, and subsequently the occurrence of stroke, both the first and repeated.Conclusion. An important result of this study is the first registered change in the coagulation link of hemostasis in patients with HTN and MFA aged from 40 to 70 years, which can be considered an additional criterion for stroke prediction.

Comparison of thrombodynamic methods and routine hemostasis tests in the evaluation of hypercoagulable syndrome in chronic glomerulonephritis

Nephrotic syndrome (NS) is associated with a high risk of thrombotic complications. In this group of patients, routine local tests for assessing hemostasis do not accurately reflect hypercoagulable state. Global functional tests for assessing hemostasis, including thrombodynamics (TD), are considered promising for assessing disorders in the blood coagulation system of these patients. To compare the rate of hypercoagulability according to routine hemostatic tests and TD and to evaluate the factors associated with increased risk of thrombotic complications in patients with chronic glomerulonephritis (CGN). The study included 94 patients with active CGN who were not receiving anticoagulant therapy; 63 (80.3%) patients had NS, and 31 (19.7%) had active CGN without NS. Hemostasis parameters were assessed using local coagulation tests and TD test. Using logistic regression analysis, factors associated with the risk of thrombosis were assessed. Of the 94 patients with active CGN in 63 without preventive anticoagulant therapy, hypercoagulability according to routine tests was detected in 6 (9.5%) patients with NS and in 3 (9.7%) patients without NS (p<0.05). Hypercoagulability according to the TD test was detected in 24 (53.9%) patients with NS and in 5 (32.2%) without NS (p<0.05). The formation of spontaneous clots was observed in 29 (30.9%) of patients with CGN, most of them 24 (83%) with NS. 10.6% of patients in our cohort experienced thromboembolic events. The risk of thromboembolic events according to the univariate regression analysis was associated with older age, higher lipid levels, use of glucocorticosteroids and detection of spontaneous clots by the TD test. No association of thromboembolic events with abnormalities in routine hemostasis tests was obtained. In patients with CGN with nephrotic syndrome, hypercoagulability is detected in 9.5% of cases with routine coagulation tests and in 53.9% of cases with TD test. Detection of spontaneous clots by TD test is associated with a risk of thromboembolic events.

GWAS-significant loci and severe COVID-19: analysis of associations, link with thromboinflammation syndrome, gene-gene, and gene-environmental interactions.

The aim of this study was to replicate associations of GWAS-significant loci with severe COVID-19 in the population of Central Russia, to investigate associations of the SNPs with thromboinflammation parameters, to analyze gene-gene and gene-environmental interactions. DNA samples from 798 unrelated Caucasian subjects from Central Russia (199 hospitalized COVID-19 patients and 599 controls with a mild or asymptomatic course of COVID-19) were genotyped using probe-based polymerase chain reaction for 10 GWAS-significant SNPs: rs143334143 CCHCR1, rs111837807 CCHCR1, rs17078346 SLC6A20-LLZTFL1, rs17713054 SLC6A20-LLZTFL1, rs7949972 ELF5, rs61882275 ELF5, rs12585036 ATP11A, rs67579710 THBS3, THBS3-AS1, rs12610495 DPP9, rs9636867 IFNAR2. SNP rs17713054 SLC6A20-LZTFL1 was associated with increased risk of severe COVID-19 in the entire group (risk allele A, OR = 1.78, 95% CI = 1.22-2.6, p = 0.003), obese individuals (OR = 2.31, 95% CI = 1.52-3.5, p = 0.0002, (p bonf = 0.0004)), patients with low fruit and vegetable intake (OR = 1.72, 95% CI = 1.15-2.58, p = 0.01, (p bonf = 0.02)), low physical activity (OR = 1.93, 95% CI = 1.26-2.94, p = 0.0035, (p bonf = 0.007)), and nonsmokers (OR = 1.65, 95% CI = 1.11-2.46, p = 0.02). This SNP correlated with increased BMI (p = 0.006) and worsened thrombodynamic parameters (maximum optical density of the formed clot, D (p = 0.02), delayed appearance of spontaneous clots, Tsp (p = 0.02), clot size 30min after coagulation activation, CS (p = 0.036)). SNP rs17078346 SLC6A20-LZTFL1 was linked with increased BMI (p = 0.01) and severe COVID-19 in obese individuals (risk allele C, OR = 1.72, 95% CI = 1.15-2.58, p = 0.01, (p bonf = 0.02)). SNP rs12610495 DPP9 was associated with increased BMI (p = 0.01), severe COVID-19 in obese patients (risk allele G, OR = 1.48, 95% CI = 1.09-2.01, p = 0.01, (p bonf = 0.02)), and worsened thrombodynamic parameters (time to the start of clot growth, Tlag (p = 0.01)). For rs7949972 ELF5, a protective effect against severe COVID-19 was observed in non-obese patients (effect allele T, OR = 0.67, 95% CI = 0.47-0.95, p = 0.02, (p bonf = 0.04)), improving thrombodynamic parameters (CS (p = 0.02), stationary spatial clot growth rates, Vst (p = 0.02)). Finally, rs12585036 ATP11A exhibited a protective effect against severe COVID-19 in males (protective allele A, OR = 0.51, 95% CI = 0.32-0.83, p = 0.004). SNPs rs67579710 THBS3, THBS3-AS1, rs17713054 SLC6A20-LZTFL1, rs7949972 ELF5, rs9636867 IFNAR2-were involved in two or more of the most significant G×G interactions (p perm ≤ 0.01). The pairwise combination rs67579710 THBS3, THBS3-AS1 × rs17713054 SLC6A20-LZTFL1 was a priority in determining susceptibility to severe COVID-19 (it was included in four of the top five most significant SNP-SNP interaction models). Overall, this study represents a comprehensive molecular-genetic and bioinformatics analysis of the involvement of GWAS-significant loci in the molecular mechanisms of severe COVID-19, gene-gene and gene-environmental interactions, and provides evidence of their relationship with thromboinflammation parameters in patients hospitalized in intensive care units.

Prothrombotic state in rheumatoid arthritis

Aim. To study the indices of standard coagulogram and thrombodynamics test in native plasma and in the test with phospholipids in relation to the activity of rheumatoid arthritis (RA) and the ongoing therapy.Material and methods. We examined 28 patients with rheumatoid arthritis and eight age- and sex-matched healthy controls: 11 patients with high rheumatoid arthritis activity (DAS28&gt;5.2) (Group 1), nine patients with low and moderate rheumatoid arthritis activity (DAS28&lt;5.2) (Group 2) and eight rheumatoid arthritis patients receiving anticoagulants (Group 3). Results. Elevated fibrinogen was more common in the RA patient groups: 5/11(45%) in group 1, 3/9(33%) in group 2 and 3/8(38%) in group 3. In the control group, fibrinogen was normal, p&gt;&lt;0.05. Increased SFMC was found in all patients in all three groups (100%) and only in 2 of the controls (25%), with p&gt;&lt;0.05. Mean clot density was significantly higher in RA groups than in controls: 26811, 25437 and 24740 versus 20631 c.u. in groups 1, 2, 3 and control, respectively, p&gt;&lt;0,01. In patients with anticoagulants, lag time (1.4 minutes) was longer than without anticoagulants (1.1-1.2 minutes), with p&gt;&lt;0.05 in all cases. Spontaneous clots were detected only in patients: 3 in groups 1 and 1 each in groups 2 and 3. Hypocoagulation was detected only in group 3 in 1/8(12%) patients, and thrombotic readiness status was detected in groups 1 and 2: in 2/11(18%) and 1/9(11%) patients, respectively. The frequency of normal- and hypercoagulation did not differ between the patient and control groups. Conclusion. According to the thrombodynamics test, hypercoagulability is present in RA patients. Thrombodynamics test can be used to identify the risk of thrombosis and to individualize therapy in RA patients. Keywords: prothrombotic state, hypercoagulation, rheumatoid arthritis, thrombodynamics&gt;˂ 5.2) (Group 2) and eight rheumatoid arthritis patients receiving anticoagulants (Group 3).Results. Elevated fibrinogen was more common in the RA patient groups: 5/11(45%) in group 1, 3/9(33%) in group 2 and 3/8(38%) in group 3. In the control group, fibrinogen was normal, p˂ 0.05. Increased SFMC was found in all patients in all three groups (100%) and only in 2 of the controls (25%), with p˂ 0.05. Mean clot density was significantly higher in RA groups than in controls: 26811, 25437 and 24740 versus 20631 c.u. in groups 1, 2, 3 and control, respectively, p˂ 0,01. In patients with anticoagulants, lag time (1.4 minutes) was longer than without anticoagulants (1.1-1.2 minutes), with p˂ 0.05 in all cases. Spontaneous clots were detected only in patients: 3 in groups 1 and 1 each in groups 2 and 3. Hypocoagulation was detected only in group 3 in 1/8(12%) patients, and thrombotic readiness status was detected in groups 1 and 2: in 2/11(18%) and 1/9(11%) patients, respectively. The frequency of normal- and hypercoagulation did not differ between the patient and control groups.Conclusion. According to the thrombodynamics test, hypercoagulability is present in RA patients. Thrombodynamics test can be used to identify the risk of thrombosis and to individualize therapy in RA patients.

Children and Snakebite: Snake Venom Effects on Adult and Paediatric Plasma.

Snakebite is a globally neglected tropical disease, with coagulation disturbances being the primary pathology of many deadly snake venoms. Age-related differences in human plasma have been abundantly reported, yet the effect that these differences pose regarding snakebite is largely unknown. We tested for differences in coagulotoxic effects (via clotting time) of multiple snake venoms upon healthy human adult (18+) and paediatric (median 3.3 years old) plasma in vivo and compared these effects to the time it takes the plasmas to clot without the addition of venom (the spontaneous clotting time). We tested venoms from 15 medically significant snake species (from 13 genera) from around the world with various mechanisms of coagulotoxic actions, across the three broad categories of procoagulant, pseudo-procoagulant, and anticoagulant, to identify any differences between the two plasmas in their relative pathophysiological vulnerability to snakebite. One procoagulant venom (Daboia russelii, Russell's Viper) produced significantly greater potency on paediatric plasma compared with adult plasma. In contrast, the two anticoagulant venoms (Pseudechis australis, Mulga Snake; and Bitis cornuta, Many-horned Adder) were significantly more potent on adult plasma. All other procoagulant venoms and all pseudo-procoagulant venoms displayed similar potency across both plasmas. Our preliminary results may inform future studies on the effect of snake venoms upon plasmas from different age demographics and hope to reduce the burden of snakebite upon society.

Cloud serpent coagulotoxicity: The biochemical mechanisms underpinning the anticoagulant actions of Mixcoatlus and Ophryacus venoms

Mexico is home to an extreme diversity of herpetofauna, with venomous snakes imposing a significant burden upon public health. However, little is known about the pathophysiological venom actions of a number of potentially medically important species, including those from the genera Mixcoatlus and Ophryacus. Our study aimed to fill this knowledge gap by ascertaining the effects of Mixcoatlus melanurus, Ophryacus smaragdinus and Ophryacus sphenophrys venoms upon the coagulation cascade utilising a series of well-validated coagulation assays. While M. melanurus venom exhibited no significant coagulotoxic activities, both O. smaragdinus and O. sphenophrys venoms exerted multiple coagulotoxic activities upon the coagulation cascade which would be contributing towards a net anticoagulant venom activity. O. sphenophrys significantly inhibited the spontaneous clotting of plasma but O. smaragdinus did not. They differed in that O. sphenophrys inhibited the clotting enzymes factor IXa and factor XIa. However, O. smaragdinus was able to inhibit factor Xa in isolation-assays. Both O. smaragdinus and O. sphenophrys degraded fibrinogen, with O. smaragdinus venom causing a significantly weaker fibrinogen clot than O. sphenophrys. In vitro antivenom efficacy assays were undertaken to ascertain the efficacy of Antivipmyn-Tri antivenom (which is made using Bothrops, Crotalus, and Lachesis venoms). This antivenom was chosen due to the phylogenetic uncertain position of the Ophryacus, but with some molecular genetics’ studies placing it as sister to Lachesis. Despite the complexity of the antivenom immunising mixture, the anticoagulant activity of O. sphenophrys venom was relatively poorly neutralised by the antivenom. This work contributes to the understanding of the functional activity of Mixcoatlus and Ophryacus venoms, laying a foundation for future work investigating the coagulotoxins present within Ophryacus venoms in addition to providing data useful for the evidence-based design of clinical management strategies for the envenomed patient.

A review of VEXAS syndrome in 116 French patients

British Journal of DermatologyVolume 186, Issue 3 p. e115-e115 Plain Language SummaryFree Access A review of VEXAS syndrome in 116 French patients First published: 07 March 2022 https://doi.org/10.1111/bjd.20989AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat Abstract Linked Article: Georgin-Lavialle et al. Br J Dermatol 2022; 186:564–574. Autoinflammatory syndromes are conditions in which fever and signs of inflammation occur without an infectious cause. Some of these, mostly rare, syndromes are linked to mutations (faults in genetic code) in a specific gene. VEXAS syndrome (Vacuoles, E1 Enzyme, X chromosome, Autoinflammatory, Somatic) has recently been described and linked to a mutation in the UBA1 gene, located on the X chromosome; it is therefore much commoner in men. A major feature of the condition is relapsing polychondritis (an inflammation of the cartilage particularly affecting the respiratory tract). Other features include a tendency to spontaneous blood clotting, lung inflammation, joint pains and skin lesions including vasculitis and neutrophilic dermatosis. VEXAS is often associated with myelodysplasia (premalignant changes in blood cells), and often has a poor prognosis. Treatment includes glucocorticoids and anti-inflammatory disease modifying drugs (DMARDs). In this paper from France, the authors from multiple centres of expertise in autoinflammatory diseases worked with laboratories performing UBA1 gene analysis to collect data on their patients with VEXAS syndrome over a 6-month period. The authors added lymph node enlargement and erosive arthritis to the clinical features. They identified three clusters of disease in their patients. The first had mild to moderate disease with less fever; this group was strongly linked to a mutation in UBA1, and had a relatively good outcome. The second cluster had more severe disease, including relapsing polychondritis, and myelodysplasia was common; this group had a higher mortality rate. The third group comprised older patients who presented with inflammatory features such as skin vasculitis and weight loss. The authors found that increased mortality in VEXAS syndrome was linked to involvement of lung tissue and the gastrointestinal tract (e.g. perforation of the gut). Volume186, Issue3March 2022Pages e115-e115 RelatedInformation

​Circulating Cytokines in Myocardial Infarction Are Associated With Coronary Blood Flow.

BackgroundThe level of systemic inflammation correlates with the severity of the clinical course of acute myocardial infarction (AMI). It has been shown that circulating cytokines and endothelial dysfunction play an important role in the process of clot formation. The aim of our study was to assess the concentration of various circulating cytokines, endothelial function and blood clotting in AMI patients depending on the blood flow through the infarction-related artery (IRA).MethodsWe included 75 patients with AMI. 58 presented with ST-elevation myocardial infarction (STEMI) and 17 had non-ST-elevation myocardial infarction (non-STEMI). A flow-mediated dilation test (FMD test), thrombodynamics and rotational thromboelastometry as well as assessment of 14 serum cytokines using xMAP technology were performed.FindingsNon-STEMI-patients were characterized by higher levels of MDC, MIP-1β, TNF-α. Moreover, we observed that patients with impaired blood flow through the IRA (TIMI flow 0-1) had higher average and initial clot growth rates, earlier onset of spontaneous clots, C-reactive protein (CRP) and IL-10 compared to patients with preserved blood flow through the IRA (TIMI flow 2-3). Patients with TIMI 2-3 blood flow had higher level of IP-10. IL-10 correlated with CRP and pro-inflammatory cytokines levels, initial clot growth rate and clot lysis time in TIMI 0-1 patients. All these differences were statistically significant.InterpretationWe demonstrated that concentrations of the inflammatory cytokines correlate not only with the form of myocardial infarction (STEMI or non-STEMI), but also with the blood flow through the infarct-related artery. Inflammatory response, functional state of endothelium, and clot formation are closely linked with each other. A combination of these parameters affects the patency of the infarct-related artery.

Paired and partial correlations of immune parameters of neuro-immuno-test and coagulation parameters of thrombodynamics test in children with children's autism

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. 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. 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. 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.

Blood Clotting Decreases Pulmonary Circulation during the Coronavirus Disease

Spontaneous blood clotting in pulmonary circulation caused by thrombo-inflammation is one of the main mortality causes during the COVID-19 disease. Blood clotting leads to reduced pulmonary circulation and blood oxygenation. Lung inflammation can be evaluated with noninvasive diagnostic techniques. However, the correlation of the severity of the inflammation with the pulmonary blood flow has not been established. To address this question, in this work, we develop a multiscale model taking into account the interaction of a local model of thrombus growth with 1D hemodynamics in a vessel network. Flux reduction depending on the level of lung obstruction is evaluated. In particular, the model obtains that an obstruction level of 5% leads to a 12% reduction of blood flux. The suggested approach can be used to investigate the interaction of blood clotting and flow not only in the pulmonary network but also in other complex vessel networks.

Plasmatic and cell-based enhancement by microparticles originated from platelets and endothelial cells under simulated in vitro conditions of a dilutional coagulopathy

BackgroundAggressive fluid management and other external factors may lead to hypothermia, acidosis and hemodilution (defined as Lethal Triad, LT) contributing to a trauma-induced coagulopathy (TIC) that worsens patients’ outcomes. Procoagulant microparticles (MP) are crucial players at the interface of cellular and plasmatic coagulation. However, their functions remain largely unexplored. This study aimed to characterize effects of MP subtypes and concentrations on functional coagulation under in vitro simulated conditions.MethodsBlood from eleven volunteers were collected to simulate in vitro conditions of hemodilution (HD) and LT, respectively. HD was induced by replacing a blood volume of 33% by crystalloids and for LT, samples were further processed by reducing the temperature to 32 °C and lowering the pH to 6.8. MP were obtained either from platelet concentrates (platelet-derived MP, PDMP) or from cell culture (ECV304 cells for endothelial-derived MP, EDMP) by targeted stimulation. After introducing MP to in vitro conditions, we measured their concentration-dependent effects (1.000, 10.000 and 15.000 MP/μl blood) on coagulation compared to whole blood (WB). For each condition, coagulation was characterized by flow cytometric platelet activation and by quantification of fibrin clot propagation using Thrombodynamics® technology.ResultsMP originated from platelets and endothelial cells affected blood coagulation in a concentration-dependent manner. Particularly, high PDMP quantities (10.000 and 15.000 PDMP/μl blood) significantly induced platelet activation and fibrin clot growth and size in HD conditions. In LT conditions as well, only high PDMP concentration induced platelet activation, clot growth and size. In contrast, EDMP did not induce platelet activation, but resulted in enhanced formation of spontaneous clots, irrespective of simulated condition. With increasing EDMP concentration, the time until the onset of spontaneous clotting decreased in both HD and LT conditions.DiscussionThe study demonstrates an essential role of MP within the coagulation process under simulated coagulopathic conditions. PDMP affected platelets promoting clot formation likely by providing a surface enlargement. EDMP presumably affected clotting factors of the plasmatic coagulation resulting in an increased formation of spontaneous clots.ConclusionUnder simulated conditions of a dilutional coagulopathy, MP from different cellular origin indicate a divergent but both procoagulant mechanism within the coagulation process.

СОСТОЯНИЕ СВЕРТЫВАЮЩЕЙ СИСТЕМЫ КРОВИ У ДЕТЕЙ ПРИ СОСУДИСТЫХ МАЛЬФОРМАЦИЯХ И ВОСПАЛИТЕЛЬНЫХ ЗАБОЛЕВАНИЯХ ЧЕЛЮСТНО-ЛИЦЕВОЙ ОБЛАСТИ

The article presents the results of a study of hemostasis in children with vascular malformations and inflammatory diseases of the maxillofacial region using standard and integrated methods for assessing hemostasis. Objective of the research: to assess the state of the hemostatic system in children with vascular malformations and inflammatory diseases of the maxillofacial region using standart and integrated methods. Materials and methods: on the basis of St. Vladimir's Children's Clinical Hospital in 2015–2019. А prospective open controlled comparative nonrandomized selective study of coagulological status was performed using standard coagulological tests and integral methods for assessing hemostasis (thromboelastography – TEG, thrombodynamics – TD) in 105 patients with lymphatic, lymphovenous, venous, arteriovenous vascular malformations of the head and neck (age 6 [5; 9] years), 47 children with infectious and inflammatory diseases of the maxillofacial area (age 10 [4; 17] years). The control group included 37 children (age 9 [5; 13] years). Results: according to the data, in most patients with vascular malformations, the coagulogram did not reveal pronounced shifts in hemostasis. TEG indices demonstrated hypercoagulability in vascular malformations: the onset time of clot R formation was 11,20 [8,72; 15,75] min (the norm is 9–27 min); clot K formation time was reduced to 3,90 [2,30; 6,02] min (the norm is 2–9 min). According to TD data, the process of fibrin clot growth in patients with vascular malformations accelerated: the clot V growth rate was 32,80 [28,70; 40,20] μm/min (norm 20–29 μm/min), an increase in the rate was observed mainly due to the acceleration of the clot growth initiation. The formation of spontaneous clots was noted in 32% of cases. In the group of infectious and inflammatory diseases of the maxillofacial area, the hypercoagulation was most pronounced: fibrinogen level significantly increased compared with the control group (3,21 [2,69; 4,72] g/l vs 2,69 [2,37; 3,17 ] g/l; p=0,0025). The soluble fibrin monomer complex (SFMC) indicator statistically significantly increased to 5,50 [0,00; 6,00] mg% (1,50 [0,00; 5,00] mg% in the control group, p=0,006). TEG showed a decrease in R (11,10 [8,82; 14,32] min vs 15,2 [11,8; 20,6] min; p=0,001) and K (3,65 [2,45; 5,10] min vs 6,70 [4,20; 8,25] min; p=0,0001), statistically significant compared to the control group. The alpha angle increased to 45,70 [36,20; 56,02] (30,8 [23,25; 41,15] in the control group, p=0,0001); maximum amplitude (MA) and clot density (G) increased in comparison with the control: 56,6±8,68 mm vs 48,10±6,20 mm; p=0,0001 and 6,50 [4,80; 8,00] Kd/sc vs 4,60 [3,60; 5,30] Kd/sc; p=0,0001. The TD indices in patients in this group also reflected a hypercoagulable state: the rate of V clot formation increased to 38,60 [33,00; 51,40] μm/min (30,45 [27,60; 33,30] μm/min in the control group, p&lt;0,0001); the initial rate of clot formation also increased – 63,50 [59,10; 68,62] μm/min (58,74 [56,57; 64,20] μm/min in the control group, p=0,0055); the size (CS) and density (D) of the clot increased – 1425,5 [1265,7; 1505,2] μm (1251,00 [1168,82; 1322,50] μm in the control group, p=0,0029) and 25 362,50 [21 922,00; 29 210,50] conv. units (22 883,00 [20 807,25; 24 658,64] conv. units in the control group, p=0,0208). Spontaneous clots were formed in 50% of cases. Conclusion: integral tests are a sensitive method for assessing the state of hemostasis in patients with vascular malformations and infectious and inflammatory diseases. The revealed hypercoagulable shifts in the form of clot growth rate acceleration work as the basis for a thorough dynamic assessment of the hemostasis system in children with vascular malformations and infectious-inflammatory diseases in order to prevent thrombotic complications.

The decrease in procoagulant activity of blood during combined therapy with antidepressants and antipsychotics in patients with endogenous mental disorders

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). 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). 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. 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.

Trombodynamics Method in the Assessment of Coagulation Parameters in Psychopharmacotherapy of Endogenous Mental Disorders

Background: currently, it has been proven that the pathogenesis of endogenous mental disorders is associated with the process of neuroinflammation in the brain of patients. It is also known that chronic neuroinflammation, accompanied by a violation the permeability of the blood-brain barrier. It is accompanied by the activation of platelets that generate procoagulant microparticles, which leads to a disturbance of the hemostasis system, causing an increase in blood clotting in patients. Objective: to investigate the dynamics of procoagulant activity of blood in patients with endogenous mental disorders before and after psychopharmacotherapy.Patients and methods: the study included 185 patients aged 16 to 64 years with the following mental disorders: schizophrenia with attack-like/attack-progressive/continuous type of course (F20.00–2), affective disease (F31.1–5; F32.0–3; F33.0–3), schizotypal disorder with affective fluctuations (F21.3–4). The thrombodynamic test (TD) was performed on T-2 Trombodynamis device according to the manufacturer’s instructions (Hemacore LLC, Moscow, Russia). All patients received standard pharmacotherapy according to their condition.Results: a significant decrease of procoagulant activity of spontaneous clots in the patients’ blood after psychopharmacological treatment is observed. Our data on the positive dynamics of changes in the values of TD test’s indicators in most of the examined patients suggest that a decrease in the coagulation activity of the patients’ blood as a result of treatment may be associated with the anti- inflammatory effect of antipsychotics and antidepressants.Conclusion: for the first time, it was shown that there is a positive dynamic in changing the values of the main parameters of the TD test in most patients with endogenous mental diseases. The results of TD tests can be the basis for monitoring the response to therapy.

PMD28 Systematic Review on the Clinical Efficacy of the Thrombodynamics Analyser System

To conduct a systematic review of the literature on the clinical efficacy of the Thrombodynamics Analyser System (TD) for the evaluation of the coagulation state of the blood. We searched Medline, the Cochrane Library, and Russian database eLIBRARY for clinical studies reported comparative efficacy of TD as an additional test to other methods for evaluating the hemostasis system. The search was conducted in April 2019 and included studies published in English or Russian. 363 citations were found (104 in Medline and the Cochrane Library, 132 references in eLIBRARY and 127 publications in references), of which six relevant publications were included. Five studies evaluated the effectiveness of TD for assessing the risk of venous thromboembolic complications (VTEC) and one study assessed the effectiveness of TD for predicting the success of in vitro fertilization (IVF) procedures. Initial clot growth rate (Vi, μm / min) (Lobastov K. et al., 2020; Katelnitskaya O.V. et al., 2017), the stationary clot growth rate (Vs, μm / min) (Lobastov K. et al., 2020), the appearance of spontaneous clots (SC, %) Katelnitskaya O.V. et al. (2017), the clot growth rate (V, μm / min) (Silina et al., 2016), the measurement results of TD, were predictor markers of VTEC in the postoperative period. The clot growth rate (V, μm / min) > 32.3 μm/min before IVF was a predictor of a negative outcome of IVF (RR = 1.41; 95% CI 1.2 - 1.67; p <0.001) (Balandina A.N. et al., 2019). Two studies did not evaluate the relationship between the TD test parameters and the hemostatic system with at least one final outcome. The results of this systematic review can be used to estimate the cost-effectiveness of TD for predicting VTEC in the postoperative period or the success of IVF.

Изменения в системе гемостаза у беременных с задержкой роста плода

Введение: Задержка роста плода (ЗРП) занимает второе место в структуре причин перинатальной смертности, а ее наличие имеет длительное неблагоприятное влияние на здоровье ребенка. Оценка степени активации системы гемостаза при ЗРП в сопоставлении с клиническими исходами имеет важное значение в понимании патогенеза, улучшении прогнозирования и профилактики этого патологического состояния. Цель исследования: оценить состояние гемостаза у беременных с ЗРП в сравнении с женщинами с физиологическим течением беременности. Материалы и методы: Тип исследования: поперечный срез на базе когортного. В исследование включено 52 беременных. Основная группа — 32 пациентки с ЗРП, выявленной при ультразвуковой фетометрии; контрольная группа — 20 практически здоровых женщин без отягощенного акушерско-гинекологического анамнеза, с физиологически протекавшей беременностью, завершившейся неосложненными родами. Оценку состояния системы гемостаза проводили на сроке 24-32 нед гестации. Результаты: Среди факторов тромботического риска у беременных с ЗРП чаще выявлялось табакокурение во время беременности. Наличие ЗРП было значимо связано с маловодием, генитальной и внутриматочной инфекцией, преэклампсией, нарушениями маточно-плацентарно-плодового кровотока. У женщин с ЗРП обнаружен более высокий уровень фибриногена, а также повышение скорости роста сгустка, больший размер сгустка, более частое формирование спонтанных сгустков в сравнении с контрольной группой. Заключение: У беременных с ЗРП имеется протромботическая готовность плазмы, что может служить основанием для дальнейшей разработки антитромботической коррекции с целью улучшения перинатальных исходов. Background: Fetal growth retardation (FGR) is the second leading cause of perinatal mortality, has a long-term adverse effect on child health. Assessment of hemostasis activation in FGR in comparison with clinical outcomes is important for understanding pathogenesis, improving the prognosis and prevention of this pathological state. Objectives: to assess hemostasis state in pregnant women with FGR compared to women with physiological pregnancy. Patients/Methods: Type of study: crosssectional based on cohort. The study included 52 pregnant women. The main group consisted of 32 patients with FGR diagnosed by ultrasound fetometry; the control group consisted of 20 practically healthy women without burdened obstetric-gynecological history, with physiological pregnancy that ended in uncomplicated childbirth. Hemostasis assessment was carried out at 24-32 weeks of gestation. Results: Smoking during pregnancy as a factor of thrombotic risk was more common in pregnant women with FGR. FGR was significantly associated with oligohydramnios, genital and intrauterine infection, preeclampsia, and placental insufficiency. Women with FGR showed a higher level of fibrinogen, as well as an increased rate of clot growth, clot larger size, and more frequent formation of spontaneous clots in comparison with the control group. Conclusions: Pregnant women with FGR are characterized by prothrombotic state that may be the basis for further development of antithrombotic correction for improving perinatal outcomes.

Pets in peril: The relative susceptibility of cats and dogs to procoagulant snake venoms

Snakebite is a common occurrence for pet cats and dogs worldwide and can be fatal. In Australia the eastern brown snake (Pseudonaja textilis) is responsible for an estimated 76% of reported snakebite cases to domestic pets nationally each year, with the primary pathology being venom-induced consumptive coagulopathy. While only 31% of dogs survive P. textilis bites without antivenom, cats are twice as likely to survive bites (66%). Even with antivenom treatment, cats have a significantly higher survival rate. The reason behind this disparity is unclear. Using a coagulation analyser (Stago STA R Max), we tested the relative procoagulant effects of P. textilis venom—as well as 10 additional procoagulant venoms found around the world—on cat and dog plasma in vitro, as well as on human plasma for comparison. All venoms acted faster upon dog plasma than cat or human, indicating that dogs would likely enter coagulopathic states sooner, and are thus more vulnerable to procoagulant snake venoms. The spontaneous clotting time (recalcified plasma with no venom added) was also substantially faster in dogs than in cats, suggesting that the naturally faster clotting blood of dogs predisposes them to being more vulnerable to procoagulant snake venoms. This is consistent with clinical records showing more rapid onset of symptoms and lethal effects in dogs than cats. Several behavioural differences between cats and dogs are also highly likely to disproportionately negatively affect prognosis in dogs. Thus, compared to cats, dogs require earlier snakebite first-aid and antivenom to prevent the onset of lethal venom effects.

Tyrosine Kinase Inhibitor-Induced Colitis as a Rare Cause of Bloody Diarrhea

A45-year-old woman was hospitalized in the emergency room because of bloody diarrhea with severe abdominal pain. For the previous 2 weeks, the patient had been taking the selective tyrosine kinase inhibitor (TKI) dasatinib (100 mg once daily) for Philadelphia chromosome-positive acute lymphoblastic leukemia. A colonoscopy showed numerous erosions/ulcers with spontaneous oozing, bleeding, and surface hemorrhagic clots, as well as many yellowish exudative plaques from the transverse colon to the rectum (Figure A and B, Video 1).