Thrombomodulin Levels Research Articles

High plasma thrombomodulin level is associated with a decreased risk of cognitive impairment after ischemic stroke

BackgroundThrombomodulin, a thrombin receptor with anticoagulant, anti-inflammatory, and cytoprotective properties, has been suggested to play a pivotal role in ischemic stroke. However, the association of plasma thrombomodulin with post-stroke cognitive impairment (PSCI) remains unclear. We aimed to prospectively investigate the associations of plasma thrombomodulin with PSCI among ischemic stroke patients in a multicenter cohort study. MethodsWe measured plasma thrombomodulin levels at baseline among 615 ischemic stroke patients from a preplanned ancillary study of the CATIS (China Antihypertensive Trial in Acute Ischemic Stroke). We used Montreal Cognitive Assessment (MoCA) to evaluate cognitive function at 3-month follow-up after ischemic stroke, and PSCI was defined as MoCA score <23. ResultsPlasma thrombomodulin was inversely associated with PSCI, and the adjusted odds ratio of PSCI for the highest versus lowest quartile of thrombomodulin was 0.50 (95% CI: 0.28-0.92, Ptrend=0.026). Each standard deviation increment of log-transformed thrombomodulin was associated with a 23% (odds ratio: 0.77, 95% CI: 0.62-0.97, P=0.029) decreased risk of PSCI. In addition, plasma thrombomodulin could significantly improve the risk reclassification of PSCI beyond established risk factors (net reclassification index: 25.04%, 95% CI: 7.20%-42.87%, P=0.007; integrated discrimination improvement: 1.13%, 95% CI: 0.18%-2.09%, P=0.020). ConclusionsHigh plasma thrombomodulin levels were associated with a decreased risk of PSCI among ischemic stroke patients. Our findings suggest that plasma thrombomodulin might be a predictive biomarker and potential therapeutic target for PSCI.

Endothelial function in patients after severe or critical acute phase of COVID-19 one year after the disease onset

BACKGROUND. The SARS-CoV-2 virus not only causes respiratory diseases but also significantly impacts endothelial function, which may be one of the mechanisms for developing long-term consequences of coronavirus disease (COVID-19). OBJECTIVE. To determine the levels of endothelial function markers (endothelin-1, thrombomodulin) in the peripheral blood of individuals who experienced non-hospital pneumonia on the background of COVID-19, in the early post-acute phase and one year after the onset of the disease, and to analyze the changes in individual levels of these markers. MATERIALS AND METHODS. The main group consisted of 16 individuals (age – 57.5 (43.8; 64.5) years, 8 (50.0 %) men, 7 (50.0 %) women), who were examined twice: at visit 1 – on day 60.0 (56.3; 62.5) from the onset of the disease; at visit 2 – on day 312.5 (300.0; 365.0) from the onset of the disease. The control group consisted of 10 individuals (age – 58.5 (39.5; 67.8) years, 4 (40.0 %) men, 6 (60.0 %) women). General clinical and laboratory methods were used, as well as an assessment of lung diffusion capacity (DLсо). RESULTS. At visit 1, the clinical status of 16 (100.0 %) individuals in the main group was impaired. At visit 2, the clinical status of 12 (75.0 %) individuals normalized, while 4 (25.0 %) individuals showed improvement; the severity of dyspnea according to the mMRC scale and heart rate decreased, and SpO2 and DLсо levels increased (p&lt;0.01, p&lt;0.01, p&lt;0.01, and p=0.03, respectively). The level of endothelin-1 in the control group was 14.6 (11.7; 17.0) pg/ml, and the thrombomodulin level was 451.7 (403.9; 652.4) pg/ml. The level of endothelin-1 at visit 1 in the main group was 11.1 (6.8; 15.9) pg/ml, and at visit 2 – 14.4 (11.2; 20.0) pg/ml (p=0.02), not differing from the control group (p=0.48 and p=0.61, respectively). The level of thrombomodulin at visit 1 in the main group was 723.1 (689.1; 1012.2) pg/ml, and at visit 2 – 811.5 (713.3; 911.7) pg/ml (p=0.40), which was higher than in the control group (p=0.01 and p=0.01, respectively). CONCLUSIONS. One year after COVID-19, most individuals show normalization of clinical status and improvement in lung diffusion capacity; however, elevated thrombomodulin levels persist, which requires further investigation. In some patients, the level of endothelin-1 also increases, which is why they should be monitored not only by a family doctor or a pulmonologist but also by a cardiologist.

A single-center study of reference intervals for TAT, PIC, TM and t-PAIC in healthy older Chinese adults

ObjectiveTo explore the distribution of thrombin–antithrombin complex (TAT), plasmin-α2-antiplasmin inhibitor complex (PIC), thrombomodulin (TM), and tissue plasminogen activator-inhibitor complex (t-PAIC) in healthy older Chinese adults, and establish the reference intervals (RIs).MethodsThe Biotech Shine i2900 chemiluminescence immune assay was used to measure the plasma concentrations of TAT, PIC, TM, and t-PAIC in 1628 adults ≥ 60 years. The RIs were established using the 2.5th and 97.5th percentiles of the distribution.ResultsTAT levels were lower in males than females across all ages. Differences between the ages of 60–79 and ≥ 80 in both sex groups were statistically significant, with an upward trend with age. PIC levels showed no difference between the sexes but increased with age in both groups. TM levels did not differ between the sex groups, with slight fluctuation with age. The level in females aged 60–69 was slightly higher than that in the other groups; the difference was statistically significant. T-PAIC levels were not significantly different between the sex groups, with less fluctuation with sex and age. The level in males ≥ 80 years old was slightly lower than that in the other groups; the difference was statistically significant. The RIs for all markers in healthy older Chinese adults were determined and statistically reported by age and sex. For TAT, the RIs for males aged 60–79 and ≥ 80 are 0.51–2.30 ng/mL and 0.88–3.72 ng/mL, respectively, whereas for females aged 60–79 and ≥ 80, the RIs are 0.68–2.82 ng/mL and 1.02–3.67 ng/mL, respectively. For PIC, the RIs for the age groups 60–69, 70–79, and ≥ 80 are 0.10–0.89 µg/mL, 0.12–1.00 µg/mL, and 0.21–1.04 µg/mL, respectively. The RI of TM for females aged 60–69 is 3.32–13.22 TU/mL, whereas it is 2.96–13.26 TU/mL for the other groups. The RI of t-PAIC for males aged ≥ 80 is 1.63–10.68 ng/mL, whereas it is 2.33–11.34 ng/mL for the other groups.ConclusionsDiscrepancies exist in thrombus markers among different sex and age groups. The RIs of TAT, PIC, TM and t-PAIC for healthy older Chinese adults were successfully established.

Iloprost and Organ Dysfunction in Adults With Septic Shock and Endotheliopathy

Soluble thrombomodulin is a marker of endotheliopathy, and iloprost may improve endothelial function. In patients with septic shock, high plasma levels of soluble thrombomodulin (>10 ng/mL) have been associated with worse organ dysfunction and mortality. To assess the effects of treatment with iloprost vs placebo on the severity of organ failure in patients with septic shock and plasma levels of soluble thrombomodulin higher than 10 ng/mL. This investigator-initiated, adaptive, parallel group, stratified, double-blind randomized clinical trial was conducted between November 1, 2019, and July 5, 2022, at 6 hospitals in Denmark. The trial had a maximum sample size of 380, with an interim analysis for futility only at 200 patients with 90 days of follow-up. In total, 279 adults in the intensive care unit (ICU) with septic shock and endotheliopathy were included. Patients were randomized 1:1 to masked intravenous infusion of iloprost, 1 ng/kg/min (n = 142), or placebo (n = 137) for 72 hours. The primary outcome was mean daily Sequential Organ Failure Assessment (SOFA) score in the ICU adjusted for trial site and baseline SOFA score for the per-protocol population. SOFA scores for each of the 5 organ systems ranged from 0 to 4, with higher scores indicating more severe dysfunction (maximum score, 20). The secondary outcomes included serious adverse reactions and serious adverse events at 7 days and mortality at 90 days. Of 279 randomized patients, data from 278 were analyzed (median [IQR] age, 69 [58-77] years; 171 (62%) male), 142 in the iloprost group and 136 in the placebo group. The trial was stopped for futility at the planned interim analysis. The mean [IQR] daily SOFA score was 10.6 (6.4-14.8) in the iloprost group and 10.5 (5.9-15.5) in the placebo group (adjusted mean difference, 0.2 [95% CI, -0.8 to 1.2]; P = .70). Mortality at 90 days in the iloprost group was 57% (81 of 142) vs 51% (70 of 136) in the placebo group (adjusted relative risk, 1.12 [95% CI, 0.91-1.40]; P = .33). Serious adverse events occurred in 26 of 142 patients (18%) for the iloprost group vs 20 of 136 patients (15%) for the placebo group (adjusted relative risk, 1.25 [95% CI, 0.73-2.15]; P = .52). Only 1 serious adverse reaction was observed. In this randomized clinical trial of adults in the ICU with septic shock and severe endotheliopathy, infusion of iloprost, 1 ng/kg/min, for 72 hours did not reduce mean daily SOFA scores compared with placebo. In a clinical context, administration of iloprost will be unlikely to improve outcome in these patients. ClinicalTrials.gov Identifier: NCT04123444.

Serum levels of biomarkers related to severity staging of Raynaud’s phenomenon, neurosensory manifestations, and vibration exposure in patients with hand-arm vibration injury

Our aim was to explore possible relationships between serum levels of biomarkers in patients with hand-arm vibration injury in relation to the severity of the vascular, i.e., Raynaud’s phenomenon (RP), and neurosensory manifestations, the current exposure level, and the duration of exposure. This study was of case series design and involved 92 patients diagnosed with hand-arm vibration injury. Jonckheere’s trend test was used to assess any association between serum levels of biomarkers and RP as well as neurosensory manifestations, graded by the International Consensus Criteria. Generalized linear models with adjustment for possible confounders were also used for associations between serum levels of biomarkers and; (1) severity of RP recorded as the extent of finger blanching calculated with Griffin score, (2) vibration perception thresholds, (3) magnitude of current exposure as [A(8); (m/s2)] value, and (4) the duration of exposure in years. Serum levels of thrombomodulin, von Willebrand factor, calcitonin gene related peptide (CGRP), heat shock protein 27, and caspase-3 were positively associated with severity of RP. Serum levels of CGRP were positively associated with the neurosensory component. No associations with exposure were shown for these biomarkers. For Intercellular adhesion molecule 1 and monocyte chemoattractant protein 1, no associations were found with neither severity nor exposure. Levels of serum biomarkers associated with endothelial injury or dysfunction, inflammation, vasodilation, neuroprotection, and apoptosis were positively associated with the severity of hand-arm vibration injury.

Extended survival of 9- and 10-gene-edited pig heart xenografts with ischemia minimization and CD154 costimulation blockade-based immunosuppression

BackgroundXenotransplantation has made significant advances recently using pigs genetically engineered to remove carbohydrate antigens, either alone or with addition of various human complement, coagulation, and anti-inflammatory ‘transgenes’. Here we evaluated results associated with gene-edited (GE) pig hearts transplanted in baboons using an established costimulation-based immunosuppressive regimen and a cold-perfused graft preservation technique. MethodsEight baboons received heterotopic abdominal heart transplants from 3-GE (GalKO.β4GalNT2KO.hCD55, n=3), 9-GE (GalKO.β4GalNT2KO.GHRKO.hCD46.hCD55. TBM.EPCR.hCD47.HO-1, n=3) or 10-G (9-GE+CMAHKO, n=2) pigs using Steen’s cold continuous perfusion for ischemia minimization. Immunosuppression (IS) included induction with anti-thymocyte globulin and αCD20, ongoing αCD154, MMF, and tapered corticosteroid. ResultsAll three 3-GE grafts functioned well initially, but failed within 5 days. One 9-GE graft was lost intraoperatively due to a technical issue and another was lost at POD 13 due to antibody mediated rejection (AMR) in a baboon with a strongly positive pre-operative cross-match. One 10-GE heart failed at POD113 with combined cellular and antibody mediated rejection. One 9-GE and one 10-GE hearts had preserved graft function with normal myocardium on protocol biopsies, but exhibited slowly progressive graft hypertrophy until elective necropsy at POD393 and 243 respectively. Elevated levels of IL-6, MCP-1, C-reactive protein, and human thrombomodulin were variably associated with conditioning, the transplant procedure, and clinically significant postoperative events. ConclusionRelative to reference genetics without thrombo-regulatory and anti-inflammatory gene expression, 9- or 10-GE pig hearts exhibit promising performance in the context of a clinically applicable regimen including ischemia minimization and αCD154-based IS, justifying further evaluation in an orthotopic model.

Endothelial injury and decline in lung function in persons living with HIV: a prospective Danish cohort study including 698 adults.

Endothelial injury may promote declining lung function. We aimed to investigate in well-treated persons living with HIV (PLWH) whether elevated levels of thrombomodulin (TM) and syndecan-1 (SDC1) are associated with excess lung function decline and worsening dyspnea. A prospective cohort study comprising patients from the Copenhagen municipality. We included 698 PLWH with undetectable viral load. Biomarkers and demographics were measured at baseline, spirometry [forced expiratory volume in one second (FEV1) and forced vital capacity (FVC)] and dyspnea score both at baseline and 2-year follow-up.Both biomarkers were dichotomized at the 3rd quartile. Decline in lung function was estimated using a linear mixed model with patient-specific random effect. Increase in dyspnea score was estimated using a general mixed logistic regression model. We did not find an association between elevated SDC1 or TM and an excess decline in neither FEV1: SDC1: 4.5 mL/year (95% CI: -3.9-12.9, p = 0.30), TM: 2.2 mL/year (95% CI: -6.0-10.4, p = 0.60) nor FVC: SDC1: 4.1 mL/year (95% CI: -6.0-14.2, p = 0.42), TM: 1.4 mL/year (95% CI: -8.3-11.1, p = 0.78). A subgroup analysis of never-smokers was consistent with the main analysis.Likewise, we did not find any association between elevated SDC1 and TM and increase in dyspnea score: SDC1: OR 1.43 (95% CI: 0.89-2.30, p = 0.14), TM: OR 1.05 (95% CI: 0.65-1.71, p = 0.26). We did not find a significant association between elevated biomarkers of endothelial injury and decline in lung function nor dyspnea.

Thrombomodulin as a promising Marker of Endothelial Dysfunction in Hemodialysis Patients with Non Alcoholic Fatty Liver Disease

Abstract Background Non-alcoholic fatty liver disease (NAFLD) is associated with endothelial dysfunction which is a common problem in haemodialysis patients and risk for high cardiovascular mortality in haemodialysis. Thrombomodulin is a promising marker of endothelial cell injury in different pathological conditions. This study evaluates the additive effect of non-alcoholic fatty liver disease (NAFLD) in prevalent HD (hemodialysis) patients on endothelial dysfunction. Methods This is a case-control study which was conducted on 60 ESRD (end-stage renal disease) patients on conventional hemodialysis and 30 apparently healthy controls. Patients were divided into 2 groups: group A (N = 30): with NAFLD&amp; group B (N = 30): without NAFLD, excluding elderly, diabetic, chronic liver disease, advanced heart failure, active infection, COVID-19 infection and autoimmune disease&amp; patients withhemodialysiscatheters. Thrombomodulin was measured for all participants by ELISA technique. Results Thrombomodulin had the ability to detect endothelial dysfunction in patients with NAFLD at Cut off value &amp;lt;0.8 ng/ml with sensitivity 53.33, specificity 80, PPV 72.7 and NPV 63.2. On comparing Thrombomodulin in patients with NAFLD(4.378±3.762 ng/ml), Non NAFLD (1.126±0.591 ng/ml)and control (0.755±0.314ng/ml) there was significant difference (P- value&amp;lt;0.001). Post hoc analysis showed significantly high Thrombomodulin level in patients with NAFLD compared to Non NAFLD and control with p-value&amp;lt;0.001 while there was no significant difference between patients with (Non NAFLD and control) p-value 0.792. NAFLD patients with higher Thrombomodulin level have 2.5 times higher risk to have endothelial dysfunction. There was no significant correlation between Thrombomodulin and all variables in the study. Conclusions Thrombomodulin can be used as specific marker for endothelial dysfunction in hemodialysis patients with Non Alcoholic fatty liver.

The β2-adrenergic receptor agonist formoterol attenuates necrosis and apoptosis in the rat myocardium under experimental stress-induced cardiac injury.

Currently, there is no effective therapy for takotsubo syndrome (stress-induced cardiac injury in humans) in the clinics. It has previously been shown that β2-adrenergic receptor (β2-AR) agonist formoterol reduces cardiomyocyte injury in experimental takotsubo syndrome. The aim of this study was to investigate whether formoterol prevents apoptosis and necrosis of cardiomyocytes and endothelial cells in stress-induced cardiomyopathy. Stress-induced cardiac injury was induced by immobilization of rats for 2, 6, and 24 hours. The myocardium of stressed rats showed a reduction in contractility and histological manifestations of cardiomyocyte damage: karyopyknosis, perinuclear edema of cardiomyocytes and endothelial cells, and microcirculation disturbances augmented with extended exposure to stress. In addition, apoptosis of endothelial cells was detected 6hours after the onset of stress and peaked at 24 hours. Apoptosis of cardiomyocytes significantly gained only after 24 hours of stress exposure. These morphological alterations were associated with increased levels of serum creatine kinase-MB, syndecan-1, and thrombomodulin after 24 hours of stress. Administration of β2-AR agonist formoterol (50 μg/kg) four times during 24-hour stress exposure led to the improvement in myocardial inotropy, decrease in the severity of histological signatures, reduction in the number of TUNEL-positive cardiomyocytes, serum creatine kinase-MB, syndecan-1, and thrombomodulin levels. Present data suggest that apoptosis and necrosis of cardiomyocytes and necrosis of endothelial cells in stress-induced cardiac injury can be mitigated by activation of the β2-AR. However, formoterol did not eliminate completely cardiomyocyte apoptosis, histological alterations, or endothelium injury markers under stress.

Predictive value of thrombin-antithrombin III complex and tissue plasminogen activator-inhibitor complex biomarkers in assessing the severity of early-stage acute pancreatitis.

The development of acute pancreatitis (AP) is strongly linked to blood clotting and fibrinolysis issues. Modern clinical practices now utilize advanced blood markers like thrombin-antithrombin III complex (TAT), plasmin-α2-plasmin inhibitor complex, thrombomodulin (TM), and tissue plasminogen activator-inhibitor complex (t-PAIC) to assess thrombosis risk. Our study used a highly sensitive chemiluminescence technique to measure these markers in AP patients, aiming to determine their early predictive value for AP severity. There were 173 patients with AP, all of whom developed symptoms within 72h; 102 individuals had onset symptoms within 48h. The biomarkers were measured upon admission before determining the severity of AP. The levels of TAT, plasmin-α2-plasmin inhibitor complex, TM, and t-PAIC were significantly higher in the severe acute pancreatitis (SAP) group compared with the mild acute pancreatitis and moderate severe acute pancreatitis groups. For the patients within 72h of onset, TAT, TM, and t-PAIC predicted the occurrence of SAP. For the patients within 48h of onset, TAT and t-PAIC predicted the occurrence of SAP. The area under the curve (AUC) of prediction models is similar to Bedside Index for Severity in Acute Pancreatitis (BISAP) but significantly higher than C-reactive protein (P<0.05). Notably, t-PAIC had a larger AUC than TAT, BISAP, and C-reactive protein. In the initial 48h, plasma TAT and t-PAIC levels may predict the development of SAP. Within 72h, plasma levels of TAT, TM, and t-PAIC may predict the development of SAP, and the TAT+TM+t-PAIC prediction model achieved a maximum AUC of 0.915, comparable to BISAP.

The clinical significance of TAT, PIC, TM, and t-PAIC in vascular events of BCR/ABL-negative myeloproliferative neoplasms

Predicting the likelihood vascular events in patients with BCR/ABL1-negative myeloproliferative neoplasms (MPN) is essential for the treatment of the disease. However, effective assessment methods are lacking. Thrombin-antithrombin complex (TAT), plasmin-α2- plasmininhibitor complex (PIC), thrombomodulin (TM), and tissue plasminogen activator-inhibitor complex (t-PAIC) are the new direct indicators for coagulation and fibrinolysis. The aim of this study was to investigate the changes of these four new indicators in thrombotic and hemorrhagic events in BCR/ABL1-negative MPN. The study cohort of 74 patients with BCR/ABL negative myeloproliferative disorders included essential thrombocythemia, polycythemia vera, and primary myelofibrosis (PMF). A panel of 4 biomarkers, including TAT, PIC, TM, and t-PAIC were determined using Sysmex HISCL5000 automated analyzers, whereas fibrin/fibrinogen degradation products (FDP), D-dimer and Antithrombin III (ATIII) were analyzed using Sysmex CS5100 coagulation analyzer. A total of 24 (32.4%) patients experienced thrombotic events and hemorrhagic events occurred in 8 patients (10.8%). Compared to patients without hemorrhagic-thrombotic events, patients with thrombotic events had higher fibrinogen (FIB) level, FDP level and lower ATIII activity, while patients with hemorrhagic events had lower white blood cell count and hemoglobin level, higher FDP level (P < 0.05). Patients with a JAK2V617F mutation were more likely to experience thrombotic events (P < 0.05). In addtion, patients with thrombotic events had higher TAT, PIC, TM, and t-PAIC levels than patients without hemorrhagic-thrombotic events (P < 0.05), whereas patients with hemorrhagic events had a lower median value in TAT and TM (no statistical difference, P > 0.05). Patients with higher TAT, TM and t-PAIC were more likely to experience thrombotic events (P < 0.05), and only TAT was positively correlated with thrombotic events (Spearman r =0.287, P = 0.019). TAT, PIC, TM, and t-PAIC combined with ATIII and FDP have a certain value for predicting thrombosis in patients with BCR/ABL1-negative MPN. These 6 parameters are worth further exploration as predictive factors and prognostic markers for early thrombotic events.

COAGULATION AND ANTICOAGULATION PARAMETERS IN MULTIPLE SCLEROSIS PATIENTS WITH AND WITHOUT COVID-19

The aim. To investigate plasma levels of main coagulation and fibrinolytic factors in MS patients with and without COVID-19 history. Materials and methods. A total of 127 participants were enrolled in this study, including 97 MS patients and 30 healthy controls (HC). Patients with MS were divided into two groups: MS+Covid group (n=41) – patients with MS, who had a laboratory-verified diagnosis of COVID-19 in the past 3-6-month period and MS group (n=56) – patients with MS, who did not suffer from COVID-19 previously. Determination of plasma levels of prothrombin, plasminogen, tissue-type plasminogen activator (tPA), plasminogen activator inhibitor-1 (PAI-1), protein C (PC), soluble thrombomodulin (TM) was performed by means of enzyme-linked immunosorbent assay. Spectrophotometric techniques were used to determine concentrations of fibrinogen, soluble fibrin monomeric complexes (SFMC) as well as plasminogen activity and inhibitory potential of α-2-antiplasmin. Results. The MS group was characterized by elevated levels of plasma prothrombin, fibrinogen, D-dimer, SFMC, soluble TM compared to HC, while PC concentration did not differ between MS and HC groups. Plasma plasminogen level as well as plasma level of the potential plasmin activity were significantly decreased in MS patients compared to HC group. The plasma tPA level was significantly reduced while plasma PAI-I level was significantly increased in MS patients compared to HC. Patients of MS group had an increased level of plasma α-2-antiplasmin activity compared with HC group. To note, most of studied parameters did not differ between two MS groups, except protein C, soluble thrombomodulin levels and plasma α-2-antiplasmin activity. Conclusions. The results of our study showed that MS patients have got altered hemostasis parameters; however, further study is necessary to find out the relationship between particular components of coagulation and fibrinolytic systems and pathophysiology of MS. Additionally, our findings demonstrated that a SARS-CoV-2 infection had a limited effect on hemostasis parameters in MS patients, causing changes in only a few parameters, including thrombomodulin and protein C levels as well as α-2-antiplasmin activity.

Assessment of Thrombomodulin Level in Plasma of Patients with Compensated and Decompensated Liver Cirrhosis

Assessment of Thrombomodulin Level in Plasma of Patients with Compensated and Decompensated Liver Cirrhosis

Laboratory indicators of hemostasis, lipid metabolism and endothelial dysfunction in men aged 18–50 years with different subtypes of ischemic stroke

Objective: to evaluate laboratory parameters of hemostasis, lipid metabolism and endothelial dysfunction and their relationship in men aged 18–50 years with atherothrombotic (ATS), lacunar (LS) and cardioembolic (CES) stroke. Material and methods. The study included 89 men with ATS (n=36), LS (n=34) and CES (n=19). Neuroimaging, ultrasound and laboratory blood serum analyses were performed in all patients. Results. The mean age of the patients was 42.6±5.3 years. The main risk factors for ATS, LS and CES included: arterial hypertension (75; 97.8 and 73.7% of cases, respectively), dyslipidemia (60; 41.3 and 42.1%), tobacco smoking (71.7; 67.4 and 52.6%), regular alcohol consumption (35; 19.6 and 36.8%), obesity (23.3; 8.7 and 15.8 %), diabetes mellitus (8.3; 6.5 and 10.5 %). Lower tissue plasminogen activator levels were found in patients with CES (2.66±1.77 ng/ml) compared to patients with LS (3.38±3.0 ng/ml) and ATS (3.48±2.45 ng/ml). Plasminogen activator inhibitor-1 levels were significantly increased in all stroke subtypes. The mean level of soluble thrombomodulin was highest in patients with LS (100.86±58.22 pg/ml) compared to patients with ATS (96.37±85.71 pg/ml) and CES (75.28±39.36 pg/ml). The level of asymmetric dimethylarginine was higher in patients with ATS (1.46±0.42 μmol/l) and in patients with LS (0.79±0.37 μmol/l), and in patients with CES (0.4±0.13 μmol/l) it was within the reference values. Conclusion. We noted differences in laboratory parameters of the hemostasis, lipid metabolism and endothelial dysfunction in men aged 18–50 years with different stroke subtypes (ATS, LS and CES), as well as clinical and laboratory correlations.

Differential expression of serum TM, PAF, and CD62P in patients with autologous arteriovenous fistula and the correlation with vascular access function.

End-stage renal disease (ESRD) is the final stage of chronic kidney disease (CKD). We aimed to analyze the expression differences of serum thrombomodulin (TM), platelet-activating factor (PAF), and P-selectin (CD62P) in patients with autologous arteriovenous fistula (AVF) and the correlation with vascular access function. The case data were retrospectively analyzed. Moreover, 160 patients with AVF maintenance hemodialysis were selected as the AVF group, and 150 healthy participants were selected as the healthy control group. According to the function of vascular access, patients in the AVF group were divided into Group A (n = 50, after the first establishment of AVF), Group B (n = 64, normal vascular access function after hemodialysis treatment), and Group C (n = 46, vascular access failure). Pearson analysis was conducted to explore the correlation between serum TM, PAF, CD62P content, and vascular pathological examination indicators, to evaluate the value of TM, PAF, and CD62P levels in predicting vascular access failure in patients with AVF. The serum levels of TM, PAF, and CD62P were positively correlated with the expressions of CD68 and MCP-1, respectively (p < .001). Serum TM was positively correlated with the levels of PAF and CD62P (p < .001), and PAF was positively correlated with the levels of CD62P (p < .001), respectively. Serum levels of TM, PAF and CD62P were risk factors for vascular access failure in AVF patients (p < .05). The area under the curve of serum TM, PAF and CD62P levels in predicting vascular access failure in AVF patients was 0.879. The serum levels of TM, PAF, and CD62P in AVF patients were correlated with the vascular access function of AVF patients, which was very important for maintaining the stability of vascular access function, and had certain value in predicting vascular access failure/disorder in AVF patients, and could be popularized and applied.

Prognostic value of coagulation markers in patients with colorectal caner: A prospective study.

The occurrence, growth, and metastasis of colorectal cancer (CRC) are connected to the hypercoagulable state of blood (CRC). This study aimed to identify significant coagulation factors to predict metastasis and prognosis of CRC. Thrombomodulin (TM), thrombin-antithrombin complex (TAT), α2-plasmininhibitor-plasmin complex (PIC), and tissue plasminogen activator-inhibitor complex (t-PAIC) were detected by chemiluminescence immunoassay using Sysmex HISCL5000 automated analyzers. The Sysmex CS 5100 automatic blood coagulation analyzer was used to detect d-dimer (DD), fibrin degradation product (FDP), prothrombin time (PT), thrombin time (TT), international normalized ratio (INR), fibrinogen (Fbg), and activated partial thromboplastin time (APTT). Area under the curve (AUC) and the receiver operating characteristic curve (ROC) were used to assess the diagnostic efficacy of markers. Kaplan-Meier analysis was used to calculate survival probabilities. Independent prognostic factors and the nomogram were developed using single-factor and multifactor cox regression analysis model. The following indicators (TM, TAT, PIC, t-PAIC, DD, FDP, PT, INR, APTT, and Fbg) were markedly higher in CRC patients than in healthy controls, and they were higher in the metastasis (M) group than in the nonmetastasis (NM) group. The combination "TAT + PIC + DD + FDP + Fbg" can distinguish M from NM with exceptional sensitivity and specificity. Patients with CRC who had high levels of TAT, PIC, DD, FDP, Fbg, TM, tPAIC, PT, and INR had significantly shorter survival. The prognosis of CRC patients can be predicted by coagulation indicators. The independent predictive variables for overall survival were found to be TM and DD. To forecast CRC patient survival, a nomogram was created.

Thrombomodulin Serum Levels-A Predictable Biomarker for the Acute Onset of Ischemic Stroke.

The early diagnosis of acute ischemic stroke (AIS) can be challenging in cases presenting with a scarcity of clinical signs, normal cerebral imaging in early stages and a lack of specific serum markers. Thrombomodulin has been shown to be associated with cerebrovascular ischemic events and can be considered an important biomarker for the acute onset of ischemic stroke. In our study, we compared the serum levels of thrombomodulin (sTM) between a relevant patient group of 70 AIS patients and a control group of patients without AIS admitted into the neurology department between June 2022 and May 2023. sTM levels were measured at 24 h and 48 h after patients' admissions into the hospital. There was a significant difference between the two groups (AIS: 23.2 ± 9.17 ng/mL vs. controls: 3.64 ± 1.72 ng/mL; p-value < 0.001). sTM values were correlated with the score of neurological deficits, with gender and dyslipidemia. The association of sTM values with the acute onset of AIS as an end point was significant, which allows rapid therapeutic interventions, even in the absence of a well-defined clinical syndrome (AUC = 0.99). Reanalysis of the patients after propensity score matching increased the power of sTM as a biomarker (AUC = 1). sTM represents a potentially useful biomarker to diagnose the onset of an AIS, even in scarce clinical presentations, which makes thrombomodulin a valuable indicator for early treatment initiation.

Are serum thrombomodulin and interleukin-8 levels associated with disease severity and mortality in critically ill children with respiratory failure?

Thrombomodulin (TM) is found on endothelial cell surfaces and increases in response to endothelial injury of different organs. Interleukin (IL)-8 regulates pulmonary inflammation. TM and IL-8 are candidate biological markers of acute respiratory distress syndrome (ARDS). The aim of the present study was to compare TM and IL-8 levels in pediatric patients with and without ARDS who received respiratory support and to determine their relationships with prognosis. This was a prospective observational study of 55 patients who received respiratory support in the pediatric intensive care unit. Eighteen patients without active infection were defined as the control group. Two blood samples were taken for serum IL-8 and TM levels on the first and third days of respiratory support. The patient group had significantly higher IL-8 and TM levels than the control group [median IL-8: 102.7 (IQR: 180.42-189.47) vs. 45.4 (55.14-70.49) ng/L, p = 0.011; median TM: 6.9 (6.83-9.18) vs. 3.4 (3.62-5.05) ng/mL, p = 0.021]. Patients with ARDS had significantly higher marker levels on the first and third days than those who did not have ARDS. The TM and IL-8 levels of deceased patients were significantly higher than those of the survivors on the first day. In mortality prediction, the cut-off point for IL-8 was found to be >154.7 ng/L, which had sensitivity of 76.9% and specificity of 73.8%. The cut-off point for TM was >8.4 ng/mL, which had sensitivity of 76.9% and specificity of 66.7%. In our study, higher marker levels correlated with impaired oxygenation and higher mortality. Higher TM and IL-8 levels in ARDS might reflect the degree of vascular injury and inflammation.

Маркеры эндотелиальной дисфункции у реконвалесцентов коронавирусной инфекции COVID-19

Vessel endothelial dysfunction is one of the key reasons for the development of thrombosis and unfavorable outcome in patients with COVID-19 coronavirus infection. The risk of thrombosis in patients with COVID-19 may persist during the convalescence period, after discharge from hospital. The purpose — to assess hemostatis in convalescents with moderate COVID-19. Material and methods. The study of hemostasis was conducted in 32 patients aged 40 to 79 years with coronavirus infection COVID-19 during the period of convalescence, after discharge from hospital. The control group consisted of 20 healthy people of the same age. The study included determining biomarkers of endothelial dysfunction in venous blood: P-selectin, von Willebrand factor (VWF), D-dimer and thrombomodulin. Results. It was found that in 24 of 32 patients (75%) after COVID-19 the level of D-dimer was significantly higher than in the control group. Median D-dimer was elevated even 3-4 months after discharge from hospital. P-selectin levels were elevated in 12 (37%) patients who recovered from COVID-19. The median P-selectin was higher than that of the control group 3-4 months after discharge from hospital. A decrease in thrombomodulin levels was recorded in 10 patients (31%). The parameter median was lower than that in the control group only during the first 2 months after discharge from hospital. The values of the FFB factor in patients after COVID-19 did not differ from those in the control group. Conclusion. A significant proportion of convalescents with moderate COVID-19, even 3-4 months after discharge from hospital, retain endothelial dysfunction and procoagulant potential, which causes the risk of thrombotic complications.

Comparison of thrombomodulin, vWF, and ADAMTS13 levels between preeclampsia and normal pregnancy

To determine and compare plasma thrombomodulin, von Willebrand factor and von Willebrand factorcleaving protease levels between pre-eclamptic and healthy pregnant females. The cross-sectional, comparative study was conducted at the Department of Haematology, University of Health Sciences, Lahore, Pakistan, from November 2019 to December 2020, and comprised pregnant females who were divided into healthy pregnant group A and pre-eclamptic group B. Plasma thrombomodulin and von Willebrand factor-cleaving protease levels were determined by using commercially available enzyme-linked immunosorbent assay kit, and von Willebrand factor level was determined by using immuno-turbidimetric assay kit. Data was analysed using SPSS 25. Of the 88 participants, there were 44(50%) females with mean age 25.5±6 years in group A and 44(50%) in group B with mean age 26±5 years. Median thrombomodulin level in group B was significantly higher than group A (p=0.003). Median von Willebrand factor-cleaving protease levels were lower in group B compared to group A (p=0.838). A significant difference in von Willebrand factor level was observed between the groups (p=0.038). Females with pre-eclampsia had significantly higher plasma levels of von Willebrand factor and thrombomodulin than healthy pregnant subjects.