Predictive indicators in peripheral blood and left atrium blood for left atrial spontaneous echo contrast in atrial fibrillation patients.

OBJECTIVES: The purpose of this study was to demonstrate the discriminating predictive indicators in peripheral blood and left atrium blood for predicting the risk of left atrial spontaneous echo contrast (LASEC) in atrial fibrillation patients underwent catheter ablation. METHODS: A total of 108 consecutive AF patients treated with radiofrequency ablation between July 2022 and July 2023 were enrolled and divided into two groups based on preprocedural transesophageal echocardiography: the non LASEC group (n = 71) and the LASEC group (n = 37). Circulating platelet and endothelial- derived MPs (PMPs and EMPs) in peripheral blood and left atrial blood were detected. Plasma soluble P-selectin (sP-selectin) and von Willebrand factor (vWF) were observed. Diagnostic efficiency was measured using receiver operating characteristic (ROC) curve. RESULTS: Peripheral sP-selectin, vWF and EMPs expressions elevated in all subjects when compared to those in left atrium blood. Levels of sP-selectin and vWF were significantly higher in peripheral blood of LASEC group than those of non LASEC group (p = 0.0018,p = 0.0271). Significant accumulations of peripheral PMPs and EMPs were documented in LASEC group by comparison with non LASEC group (p = 0.0395,p = 0.018). The area under curve(AUC) of combined PMPs and sP-selectin in predicting LASEC was 0.769 (95%CI: 0.678-0.845, sensitivity: 86.49%, specificity: 59.15%), significantly larger than PMPs or sP-selectin alone. CONCLUSIONS: Expressions of PMPs, sP-selectin, EMPs and vWF Increased in NVAF patients with LASEC and that might be potential biomarkers for LASEC prediction.

Immunoexpression of aortic endothelial P-selectin and serum apolipoprotein A-1 levels after administration of arabica (Coffea arabica) and robusta (Coffea canephora) coffee bean extracts: In vivo study in atherosclerosis rat model.

Atherosclerosis is a leading cause of cardiovascular disease-related death worldwide. Some studies suggested that the natural ingredients in coffee may negatively affect cardiovascular diseases, while other studies indicated that coffee contains anti-inflammatory compounds that are beneficial for cardiovascular diseases. The aim of this study was to measure the expression of P-selectin in aortic endothelial cells and the level of serum apolipoprotein A-1 (ApoA-1) in an atherosclerosis rat model after the administration of arabica and robusta coffee bean extracts at mild-moderate and high doses. An experimental study was conducted with a complete randomized design using 36 adult male white rats (Rattus norvegicus) divided into six groups: negative control (NC), positive control (PC), arabica mild-moderate dose (A1), arabica high dose (A2), robusta mild-moderate dose (R1), and robusta high dose (R2). Animals were induced atherosclerosis with atherogenic feed and then were treated with arabica and robusta coffee bean extracts at two different doses for four weeks. The results showed that the expression of P-selectin in the group of rats treated with robusta coffee bean extract was lower than arabica coffee bean extract group. Rats with robusta coffee bean extract mild-moderate dose had the highest ApoA-1 levels compared to other groups significantly (p<0.05). The level of ApoA-1 was higher in both mild-moderate and high dose of robusta coffee groups compared to the negative control group (both with p<0.001). In conclusion, mild-moderate intake of robusta coffee bean extract could reduce aortic P-selectin immunoexpression and increase serum ApoA-1 levels in an atherosclerosis rat model.

Application value of P-selectin and Clara cell secretory protein 16 expression in children with severe adenovirus pneumonia.

This study investigated the roles of P-selectin and Clara cell secretory protein 16 (CC16) levels in the pathogenesis of severe adenovirus (ADV) pneumonia in children and evaluated their ability to predict disease. Fifty-one children (age, 1-5 years) with ADV pneumonia who were admitted to Xiamen Children's Hospital were included in this study and divided into the mild group (24 patients) and severe group (27 patients). A control group comprising healthy children of the same age who underwent routine physical examinations during the same period (30 patients) was also included. The univariate analysis demonstrated that the levels of the white blood cell count and C-reactive protein, procalcitonin, d-dimer, and P-selectin were increased in a severe group compared with a mild group, while CC16 levels were significantly decreased (p < 0.05). The logistic regression analysis revealed that P-selectin and CC16 levels were independent risk factors for severe ADV pneumonia in children. The areas under the ROC curves suggested that P-selectin and CC16 exhibited high predictive value for severe ADV pneumonia. P-selectin values more than 898.58 pg/mL and CC16 values less than 11.355 ng/mL predicted severe ADV pneumonia. P-selectin and CC16 levels are correlated with the severity of ADV pneumonia in children.

Platelet transfusion enhances pro-aggregatory status shortly after coronary artery bypass grafting (CABG while modulating platelet pro-inflammatory state 1-week post-surgery.

During coronary artery bypass grafting (CABG), the surgical procedure, particularly the manipulation of the major arteries of the heart, induces a significant inflammatory state that may compromise platelet function to the extent that platelet transfusion is required. Given stored platelets as a major source of biological mediators, this study investigates the effects of platelet transfusion on the major pro-aggregatory, pro-inflammatory and immunomodulatory markers of platelets. Platelets from 20 patients, 10 who received platelet transfusion and 10 without, were subjected to flow cytometery where P-selectin and CD40 ligand (CD40L) expressions and PAC-1 binding (activation-specific anti GPIIb/GPIIIa antibody) analysed at five-time points of 24 h before surgery, immediately, 2 h, 24 h and 1 week after surgery. Analysis of intra-platelet transforming growth factor-beta-1 (TGF-ß1) was also conducted using western blotting. Patients with platelet transfusion showed increased levels of P-selectin, CD40L and intra-platelet TGF-ß1 2-h after surgery compared to those without transfusion (p < 0.05). PAC-1 binding was increased 24 h after surgery in transfused patients (p < 0.05). Given the significant post-transfusion elevation of platelet TGF-ß1, P-sel/CD40L reduction in transfused patients a week after was of much interest. This study showed for the first time the significant effects of platelet transfusion on the pro-inflammatory, pro-aggeregatory and immunomodulatory state of platelets in CABG patients, which manifested with immediate, midterm and delayed consequences. While the increased pro-inflammatory conditions manifested as an immediate effect of platelet transfusion, the pro-aggregatory circumstances emerged 24 h post-transfusion. A week after surgery, attenuations of pro-inflammatory markers of platelets in transfused patients were shown, which might be due to the immunomodulatory effects of TGF-ß1.

Comparative Analysis of P-selectin Levels in Psoriasis, Vitiligo, and Nonskin Disease in a Tertiary Care Hospital: A Case-Control Study.

INTRODUCTION: The role and function of P-selectin levels in various inflammatory and immune-mediated diseases have been established. Whether they have an association with inflammatory skin diseases such as vitiligo and psoriasis needs to be established. OBJECTIVE: The objective of this study was to assess P-selectin levels in psoriasis and vitiligo and to compare them with matched controls without skin disease. MATERIALS AND METHODS: The study included a total of 90 subjects with age- and sex-matched - 30 each in psoriasis, vitiligo and 30 controls without skin disease. Psoriasis and vitiligo severity was assessed using the Psoriasis Area and Severity Index and the Vitiligo Area Scoring Index scores. P-selectin levels were assessed and compared among the groups. P-selectin levels were also compared with the severity of psoriasis and vitiligo. Chi-square and analysis of variance tests were used to compare the data. RESULTS: The mean age of subjects was 36.28 ± 11.80 years. Majority of the subjects were males (65.6%). The three groups were matched for age, sex, and other demographics. The mean P-selectin levels were 610.43 ± 134.19, 292.52 ± 60.99, and 158.97 ± 34.76 ng/ml, respectively, in the psoriasis, vitiligo, and control groups, respectively (P < 0.001). No significant association of P-selectin levels was observed with psoriasis severity; however, with increasing vitiligo severity, there was a significant increase in P-selectin levels (P < 0.001). CONCLUSION: Patients with skin diseases have raised P-selectin levels. Within skin diseases, inflammatory diseases such as psoriasis have higher P-selectin levels as compared to autoimmune diseases such as vitiligo. A significant association of P-selectin levels was observed with vitiligo severity but not with psoriasis severity.

Résumé Introduction:Le rôle et la fonction des niveaux de P-sélectine dans diverses maladies inflammatoires et à médiation immunitaire ont été établis. Si leur association avec des maladies inflammatoires de la peau telles que le vitiligo et le psoriasis doit être établie.Objectif:L'objectif L'objectif de cette étude était d'évaluer les niveaux de P-sélectine dans le psoriasis et le vitiligo et de comparer l'anthropo avec des témoins appariés sans maladie cutanée.Matériels et méthodes:L'étude a inclus un total de 90 sujets ­ 30 dans chaque groupe, des sujets de même âge et sexe atteints de psoriasis, de vitiligo. et contrôles sans maladie de peau. La gravité du psoriasis et du vitiligo a été évaluée à l'aide du Psoriasis Area and Severity Index et du Vitiligo. Scores de l'indice de notation de zone. Les niveaux de P-sélectine ont été évalués et comparés entre les groupes. Les niveaux de P-sélectine ont également été comparés aux gravité du psoriasis et du vitiligo. Des tests du chi carré et d'analyse de variance ont été utilisés pour comparer les données.Résultats:L'âge moyen des sujets était de 36,28 ± 11,80 ans. La majorité des sujets étaient des hommes (65,6 %). Les trois groupes ont été appariés en fonction de l'âge, du sexe et d'autres données démographiques. Les taux moyens de P-sélectine étaient respectivement de 610,43 ± 134,19, 292,52 ± 60,99 et 158,97 ± 34,76 ng/ml dans les patients atteints de psoriasis, de vitiligo et de contrôle. groupes, respectivement (P <0,001). Aucune association significative entre les taux de P-sélectine et la gravité du psoriasis n'a été observée; cependant, avec l'augmentation En cas de gravité du vitiligo, il y avait une augmentation significative des taux de P-sélectine ( P < 0,001).Conclusion:les patients atteints de maladies de peau ont augmenté la sélectine P les niveaux. Parmi les maladies de la peau, les maladies inflammatoires telles que le psoriasis ont des taux de sélectine P plus élevés que les maladies auto-immunes telles que comme le vitiligo. Une association significative des taux de P-sélectine a été observée avec la gravité du vitiligo mais pas avec la gravité du psoriasis.

P-selectin and C-reactive protein in relation to home blood pressure and coronary calcification: a SCAPIS substudy.

BACKGROUND: Soluble P-selectin (sP-selectin) and high-sensitivity C-reactive protein (hsCRP) have previously been associated with hypertension, but the relation with out-of-office blood pressure (BP) and coronary artery calcification score is unknown. We aimed to examine the relationship between sP-selectin, hsCRP and home BP, as well as coronary artery calcification score and carotid artery plaques. METHODS: In the Swedish CArdioPulmonary bioImage Study (SCAPIS), 5057 randomly selected participants were evaluated with office and home BP using the semi-automatic Omron M10-IT device. For this cross-sectional study, participants with sP-selectin <4 standard deviations above mean and hsCRP <5 mg/l, representing low-grade inflammation, were included. Using generalized linear models, these inflammatory markers were evaluated in relation to BP classifications, as well as coronary artery calcification score and carotid artery plaques. RESULTS: Of participants, 4548 were included in the analyses. The median age was 57.2 (53.4-61.2) years, and 775 (17.0%) reported taking medication for hypertension. Participants in the highest quartile of sP-selectin [odds ratio (OR) 1.67, 95% confidence interval (CI) 1.40-1.98, P  < 0.001] and hsCRP [OR 2.25, (95% CI 1.89-2.60), P  < 0.001] were more likely to have sustained hypertension. Participants in the highest quartile of hsCRP were also more likely to have masked hypertension, OR (95% CI) 2.31 (1.72-3.10), P  < 0.001 and carotid artery plaques, OR (95% CI) 1.21 (1.05-1.38), P  = 0.007. CONCLUSION: Increased sP-selectin and hsCRP were independently associated with sustained hypertension. These findings indicate an association between hypertension and platelet activity, as expressed by sP-selectin.

Proteomic profiling for biomarker discovery in heparin-induced thrombocytopenia.

ABSTRACT: New analytical techniques can assess hundreds of proteins simultaneously with high sensitivity, facilitating the observation of their complex interplay and role in disease mechanisms. We hypothesized that proteomic profiling targeting proteins involved in thrombus formation, inflammation, and the immune response would identify potentially new biomarkers for heparin-induced thrombocytopenia (HIT). Four existing panels of the Olink proximity extension assay covering 356 proteins involved in thrombus formation, inflammation, and immune response were applied to randomly selected patients with suspected HIT (confirmed HIT, n = 32; HIT ruled out, n = 38; and positive heparin/platelet factor 4 [H/PF4] antibodies, n = 28). The relative difference in protein concentration was analyzed using a linear regression model adjusted for sex and age. To confirm the test results, soluble P-selectin was determined using enzyme-linked immunosorbent assay (ELISA) in above mentioned patients and an additional second data set (n = 49). HIT was defined as a positive heparin-induced platelet activation assay (washed platelet assay). Among 98 patients of the primary data set, the median 4Ts score was 5 in patients with HIT, 4 in patients with positive H/PF4 antibodies, and 3 in patients without HIT. The median optical density of a polyspecific H/PF4 ELISA were 3.0, 0.9, and 0.3. Soluble P-selectin remained statistically significant after multiple test adjustments. The area under the receiver operating characteristic curve was 0.81 for Olink and 0.8 for ELISA. Future studies shall assess the diagnostic and prognostic value of soluble P-selectin in the management of HIT.

Evaluation of soluble P-selectin as a predictive biomarker in acute symptomatic pulmonary embolism: Insights from a prospective observational study.

BACKGROUND: Soluble P-selectin (sP-selectin) has been proposed as a potential biomarker for venous thromboembolism (VTE) diagnosis with interesting results. However, its role in predicting early mortality in pulmonary embolism (PE) remains unexplored. METHODS: This observational, prospective, single-center study enrolled consecutive patients aged 18 or older with confirmed acute symptomatic PE and no prior anticoagulation. The study aims to assess the prognostic capacity of sP-selectin measured at the time of PE diagnosis for short-term mortality and major bleeding. RESULTS: A total of 196 patients, with a mean age of 69.1 years (SD 17), were included, of whom 52.6% were male. Within 30 days, 9.7% of patients (n = 19) died, and 5.1% (n = 10) suffered major bleeding. PE risk stratification revealed 4.6% (n = 9) with high-risk PE, 34.7% (n = 68) with intermediate-high-risk PE, 38.3% (n = 75) with intermediate-low-risk PE, and 22.5% (n = 44) with low-risk PE according to the European Society of Cardiology score. Mean plasma sP-selectin levels were comparable between survivors and non-survivors (489.7 ng/mL ±63 vs. 497.3 ng/mL ±51; p = .9). The ROC curve for 30-day all-cause mortality and major bleeding yielded an AUC of 0.49 (95% CI 0.36-0.63) and 0.46 (95% CI 0.24-0.68), respectively. Multivariate and survival analyses were precluded due to lack of significance. CONCLUSIONS: sP-selectin was not useful for predicting short-term mortality or major bleeding in patients with acute symptomatic pulmonary embolism. Further studies are required to clarify the role of sP-selectin in VTE, particularly in prognosticating PE outcomes.

Improving platelet function following prophylactic platelet transfusion in patients with hematological malignancies.

INTRODUCTION: Platelet transfusion is a standard treatment to prevent bleeding in patients with hematological malignancies. Although transfusions can improve platelet count, their impact on platelet function remains controversial. METHODS: We conducted flow cytometry to assess platelet function before and after transfusion and performed subgroup analyses to examine differences based on blood type, corrected count increment (CCI), and platelet microparticles. RESULTS: Overall, 50 patients who received prophylactic platelet transfusion were enrolled. CD42b expression increased, whereas CD41 expression decreased after transfusion. Apheresis platelets exhibited the lowest expression of PAC-1 and P-selectin when exposed to agonist stimulations. PAC-1 expression increased under high adenosine diphosphate (ADP) stimulation, while P-selectin expression increased under both high ADP and thrombin receptor-activating peptide stimulation. In the subgroup analysis, patients with a CCI >4500 and those with the same blood types exhibited a more significant increase in PAC-1 and P-selectin expression under agonist stimulation. When comparing apheresis platelets collected on different days, only the percentage of platelet-derived microparticles showed a significant increase. CONCLUSION: Prophylactic transfusion improved platelet function. Platelet function significantly improved in patients with a CCI >4500, those with the same blood types as that of apheresis platelets, or those with platelet-derived microparticle levels <4.7%. No significant improvement in platelet function was noted after the transfusion of different blood types with acceptable compatibility or the transfusion of incompatible blood types. Our results suggest that transfusing platelets with the same blood type remains the optimal choice.

Asymmetric dimethylarginine correlates with indicators of prethrombotic state in patients with nonvalvular atrial fibrillation.

OBJECTIVE: The mechanism of asymmetric dimethylarginine (ADMA) in thrombosis in patients with nonvalvular atrial fibrillation (NVAF) is still unclear. Our aim was to investigate the relationship between ADMA and indicators of prethrombotic state in NVAF patients and to analyze the predictive role of ADMA in NVAF thrombosis. METHODS: A total of 192 NVAF patients were continuously selected from January 2023 to October 2023. Plasma ADMA levels were measured by high-performance liquid chromatography. P-selectin (P-sel), von Willebrand factor (vWF), D-dimer (D-D), and plasminogen activator inhibitor-1 (PAI-1) levels were measured by enzyme-linked immunosorbent assay (ELISA). Nitric oxide (NO) levels were measured by the nitrate reductase assay for plasma nitrite/nitrate, then the Griess method (Shanghai Hailian Biotechnology Co., Shanghai, China) was used to calculate plasma NO levels. RESULTS: In our study, ADMA levels were significantly elevated and positively correlated with P-sel, vWF, D-D, and PAI-1, whereas NO levels were significantly negatively correlated with these prethrombotic factors in NVAF. Furthermore, multifactorial logistic regression analysis showed that ADMA and LA diameter were independent predictors of high thrombosis risk (CHA2DS2-VASc ≥2 score) in patients with NVAF. CONCLUSIONS: Our findings suggested that ADMA correlated with the prethrombotic state in NVAF and that reduction of ADMA levels in NVAF patients may be a novel therapeutic strategy for thrombosis risk reduction.

Profiling plasma alterations of extracellular vesicles in patients with acutely decompensated cirrhosis and bacterial infection.

BACKGROUND: Extracellular vesicles (EVs) modulate inflammation, coagulation and vascular homeostasis in decompensated cirrhosis. AIM: To characterize the profile of plasmatic EVs in patients with decompensated cirrhosis and bacterial infections and evaluate the association between EVs and the development of hemostatic complications. METHODS: We measured the levels of EVs using high-sensitivity flow cytometry and phospholipid-dependent clotting time (PPL) in a prospective cohort of hospitalized patients with acutely decompensated cirrhosis with versus without bacterial infections. A separate cohort of patients with bacterial infections without cirrhosis was also enrolled. We measured endothelium-, tissue factor (TF)-bearing, platelet- and leukocyte-derived EVs. In patients with infections, EVs were reassessed upon resolution of infection. Bleeding and thrombotic complications were recorded during 1-year follow-up. RESULTS: Eighty patients with decompensated cirrhosis were recruited (40 each with and without bacterial infections). Electron microscopy confirmed the presence of plasma EVs. Despite no difference in total EVs and PPL, patients with cirrhosis and infection had significantly higher TF+ EVs, P-Selectin+ EVs (activated platelet-derived), CD14+ EVs (monocyte/macrophages derived) and CD14+ TF+ EVs versus those with cirrhosis without infection. Upon infection resolution, levels of these EVs returned to those without infection. Patients with infections showed a significant association between reduced P-Selectin+ EVs and bleeding complications (HR 8.0 [95%CI 1.3-48.1]), whereas high levels of leukocyte-derived EVs (CD45+) and CD14+ EVs were significantly associated with thrombotic complications (HR 16.4 [95%CI 1.7-160] and 10.9 [95%CI 1.13-106], respectively). Results were confirmed in a validation cohort. CONCLUSION: Bacterial infections are associated with particular alterations of plasma EVs profile in decompensated cirrhosis. Bacterial infections trigger the release of EVs originating from various cell types, which may tip the precarious hemostatic balance of patients with acutely decompensated cirrhosis towards hyper- or hypocoagulability.

Comprehensive investigation of platelet function in patients with cirrhosis.

Cirrhosis presents with thrombocytopenia and possibly thrombocytopathy. Previous studies exploring platelet function gave conflicting results and most controversies are explained by the variety of methods employed for investigation. We sought to assess in-vitro the overall platelet function in cirrhosis. We investigated 34 patients by using the following tests. (i)Aggregometry. (ii)Measurement of the content of platelet granules. (iii)Cytometric platelet activation. (iv)Plasmatic markers of in-vivo platelet activation. (v)Platelet procoagulant activity by thrombin generation (TG) in platelet-rich plasma (PRP). TG measured in PRP for patients and controls was similar. Platelets from patients with cirrhosis showed reduction of aggregation and secretion of ATP. Similar results were observed for platelet activation parameters such as P-selectin expression and PAC-1 platelet binding. Plasma levels of ßeta-thromboglobulin and soluble P-selectin, were increased in patients-vs-controls. In contrast, there were no patients-vs-controls differences for plasmatic platelet-factor-4. Results are consistent with a state of in-vivo platelet activation and decreased in-vitro aggregation. Since bleeding events following invasive procedures are uncommon in cirrhosis, we speculate that in-vitro aggregometry testing does not reflect the situation occurring in-vivo. Results of the study and pathophysiological considerations support the conclusion that platelet function in cirrhosis as determined by aggregometry, although somewhat impaired, may support the overall hemostatic potential, which is needed for most invasive interventions. These conclusions are in line with the recommendations of international guidelines, warning against indiscriminate use of prophylactic preprocedural administration of platelets before invasive procedures. Decision on platelet support should not be made based on in-vitro laboratory testing for platelet function.

Occult cancer in patients with unprovoked venous thromboembolism: A nested case-control study.

OBJECTIVES: Detecting occult cancer in patients with unprovoked venous thromboembolism (VTE) remains a significant challenge. Our objective was to investigate the potential predictive role of coagulation-related biomarkers in the diagnosis of occult malignancies. METHODS: We conducted a nested case-control study with a 1-year prospective cohort of 214 patients with unprovoked VTE, with a focus on identifying occult cancer. At the time of VTE diagnosis, we measured various biomarkers, including soluble P-selectin (sP-selectin), dimerized plasmin fragment D (D-dimer), platelets, leukocytes, hemoglobin, total extracellular vesicles (EVs), EVs expressing tissue factor on their surface (TF+EVs), and EVs expressing P-selectin on their surface (Psel+EVs) in all participants. RESULTS: We observed statistically significant increased levels of sP-selectin (P = .015) in patients with occult cancer. Despite an increase in Psel+EVs, TF+EVs, D-dimer, and platelets within this group, however, no significant differences were found. When sP-selectin exceeded 62 ng/mL and D-dimer surpassed 10,000 µg/L, the diagnosis of occult cancer demonstrated a specificity of up to 91% (95% CI, 79.9%-96.7%). CONCLUSIONS: The combination of sP-selectin and D-dimer can be a valuable biomarker in detecting occult cancer in patients with unprovoked VTE. Further research is necessary to ascertain whether easily measurable biomarkers such as sP-selectin and D-dimer can effectively distinguish between patients who have VTE with and without hidden malignancies.

A tight interplay between platelet activation and mitochondrial DNA release promotes platelet storage lesion in platelet concentrates.

BACKGROUND AND OBJECTIVES: Platelet storage lesion (PSL) adversely affects the quality of platelet concentrates (PCs). Platelets are prone to activation during storage. Moreover, elevated free mitochondrial DNA (mtDNA) levels in PCs are associated with a higher risk of adverse transfusion reactions. Therefore, we aimed to evaluate the correlation between platelet activation markers and mtDNA release during PC storage. MATERIALS AND METHODS: Six PCs prepared by the platelet-rich plasma method were assessed for free mtDNA copy number using quantitative real-time PCR and CD62P (P-selectin) expression by flow cytometry on days 0 (PC collection day), 3, 5 and 7 of storage. Lactate dehydrogenase (LDH) activity, pH, platelet count, mean platelet volume (MPV) and platelet distribution width (PDW) were measured as well. The correlation between free mtDNA and other PSL parameters, and the correlation between all parameters, was determined. RESULTS: Significant increases in free mtDNA, MPV and PDW, and a significant decrease in platelet count and pH were observed. CD62P expression and LDH activity elevated significantly, particularly on storage days 5-7 and 0-3, respectively. Moreover, a moderate positive correlation (r = 0.61) was observed between free mtDNA and CD62P expression. The r values between free mtDNA and LDH, pH, platelet count, MPV and PDW were 0.81, -0.72, -0.49, 0.81 and 0.77, respectively. CONCLUSION: The interplay between platelet activation and mtDNA release in promoting PSL in PCs may serve as a promising target for future research on applying additive solutions and evaluating the quality of PCs to improve transfusion and clinical outcomes.

Asymmetric Dimethylarginine Is Associated with the Phenomenon of Coronary Slow Flow in Patients with Nonvalvular Atrial Fibrillation.

INTRODUCTION: Coronary slow flow phenomena (CSFP) are associated with endothelial and blood component abnormalities in coronary arteries. Asymmetric dimethylarginine (ADMA) can damage the endothelium of the heart or blood vessels in patients with non-valvular atrial fibrillation (NVAF), causing changes in levels of biological indicators. Our aim was to analyze the relationship between ADMA and CSFP in NVAF patients. METHODS: We consecutively enrolled 134 patients diagnosed with NVAF and underwent coronary angiography, 50 control patients without a history of atrial fibrillation and with normal coronary angiographic flow were included at the same time. Based on the corrected TIMI frame count (CTFC), the NVAF patients were categorized into two groups, CTFC ≤27 frames and CTFC >27 frames. Plasma ADMA, P-selectin (p-sel), von Willebrand factor (vWF), D-dimer (D-Di), plasminogen activator inhibitor 1 (PAI-1), and nitric oxide (NO) were detected by ELISA in the different groups. RESULTS: We found that plasma ADMA levels were significantly higher among NVAF patients in the CTFC >27 grade group compared with the control or CTFC ≤27 group. In addition, the levels of blood cells and endothelium-related biomarkers (NO, P-selectin, vWF, D-Di, and PAI-1) were significantly altered and correlated with ADMA levels. Multifactorial analysis showed that plasma ADMA (odd ratio [OR; 95% CI]: 1.65 [1.21-2.43], p < 0.001) and left atrial internal diameter (OR [95% CI]: 1.04 [1.02, 1.1], p < 0.001) could be used as independent risk factors for the development of CSFP in patients with NVAF. The ROC curves of ADMA can predict the development of CSFP in NVAF patients. The minimum diagnostic concentration for the development of CSFP in patients was 2.31 µmol/L. CONCLUSION: Our study demonstrated that CSFP in NVAF patients was associated with high levels of ADMA and left atrial internal diameter. Therefore, aggressive preoperative detection and evaluation of ADMA and left atrial internal diameter can help deal with the intraoperative presence of CSFP.

Elevated Selenoprotein P Levels in Thalassemia Major Patients.

INTRODUCTION: Previous studies have measured selenium levels and glutathione peroxidase 3 (GPX3) activity in patients with thalassemia major (TM). However, Selenoprotein P (SEPP), which is responsible for the storage and transport of selenium, has not been studied in thalassemia patients. This study aims to correlate thyroid functions of TM patients with their SEPP and GPX3 levels. MATERIALS AND METHODS: Eighty subjects (40 controls, 40 TM patients) were included in this study. GPX3 and SEPP concentrations were measured in all subjects using sandwich ELISA. Iron, ferritin, urinary iodine, thyroxine (T4), triiodothyronine (T3), thyrotropin (TSH), anti-thyroid peroxidase (anti-TPO), and anti-human thyroglobulin (anti-hTG) concentrations were also measured. RESULTS: Mean SEPP concentration was higher in the TM group compared to the control group. A slight elevation in GPX3 levels was also observed in thalassemia patients, yet it was not statistically significant. In both TM patients and controls, ferritin was inversely correlated with free T4 concentration and GPX3 was inversely correlated with free T4 and T3 concentrations. There was also a negative correlation between SEPP and TSH concentrations in healthy subjects. CONCLUSION: This is the first study, which has measured SEPP concentrations in thalassemia patients. SEPP levels were higher in TM patients compared to controls. Correlations between thyroid hormones and selenoproteins may indicate that selenium is necessary for thyroid function. Detailed studies are required to elaborate the role of SEPP in thyroid metabolism in thalassemia patients.

Comparative Study on the Chronic Vascular Responses Induced by Regular Versus Occasional Waterpipe Smoke Inhalation in Mice.

BACKGROUND/AIMS: Waterpipe smoke (WPS) is the second most prevalent form of smoking in the world. There are ample evidences about the vascular alterations caused by regular WPS (Reg-WPS). Nonetheless, comparison of the chronic vascular response induced by regular versus occasional WPS (Occ-WPS) exposure is very scarce. METHODS: We investigated, in BALB/c mice, the effects of Occ-WPS (30 minutes/day, 1 day/week) versus Reg-WPS (30 minutes/day, 5 days/week) for 6 months on thrombogenicity and platelet aggregation in vivo and in vitro. Moreover, various markers of endothelial integrity, inflammation and oxidative stress were assessed by enzyme-linked immunosorbent assay and colorimetric assay. Control mice were exposed to air. RESULTS: Our results showed that either Occ-WPS or Reg-WPS exposure shortened the thrombotic time in pial microvessels in vivo. Moreover, in pial venules, this effect was more marked in Reg-WPS group (-47%) compared with Occ-WPS (-34%). Similarly, exposure to either Occ-WPS or Reg-WPS reduced the prothrombin time and activated partial thromboplastin time. Platelet count was increased only in Reg-WPS exposure. Exposure to either Occ-WPS or Reg-WPS induced platelet aggregation in vitro. In addition, there was a statistically significant difference between Occ-WPS and Reg-WPS groups in platelet count and aggregation. Plasma concentration of tissue factor (+98%), P-selectin (+14%) and E-selectin (+16%) were significantly increased in Occ-WPS group compared with air exposed group. Likewise, compared with air group Reg-WPS caused an increase in concentration of tissue factor (+193%), P-selectin (+21%) and E-selectin (+42%). Nevertheless, only Reg-WPS induced a decrease (-38%) in the plasma concentration of tissue plasminogen activator. Notably, our results showed a statistically significant difference between Occ-WPS and Reg-WPS groups in the concentration of tissue factor. Erythrocyte numbers, hemoglobin concentration, hematocrit and lactate dehydrogenase activity were augmented only in Reg-WPS group compared with either control or Occ-WPS groups. Likewise, only Reg-WPS induced an increase in proinflammatory cytokines, tumor necrosis factor-α and interleukin-1ß compared with either control or Occ-WPS groups. However, markers of oxidative stress including 8-isoprostane and total antioxidants were enhanced in both Occ-WPS and Reg-WPS compared with control group. CONCLUSION: Our data confirm the vascular toxicity of the chronic Reg-WPS exposure and shows that even occasional chronic exposure to WPS caused thrombosis, platelet aggregation, endothelial alterations and oxidative stress. The latter findings are an additional cause of concern about the long-term toxicity of occasional waterpipe smoking.

Platelets mediate inflammatory monocyte activation by SARS-CoV-2 spike protein.

Infection with SARS-CoV-2, the causative agent of COVID-19, causes mild to moderate disease in most patients but carries a risk of morbidity and mortality. Seriously affected individuals manifest disorders of hemostasis and a cytokine storm, but it is not understood how these manifestations of severe COVID-19 are linked. Here, we showed that the SARS-CoV-2 spike protein engaged the CD42b receptor to activate platelets via 2 distinct signaling pathways and promoted platelet-monocyte communication through the engagement of P selectin/PGSL-1 and CD40L/CD40, which led to proinflammatory cytokine production by monocytes. These results explain why hypercoagulation, monocyte activation, and a cytokine storm are correlated in patients severely affected by COVID-19 and suggest a potential target for therapeutic intervention.

Serum thromboxane B2 but not soluble P-selectin levels identify ischemic stroke patients with persistent platelet reactivity while on aspirin therapy.

BACKGROUND: Aspirin non-response due to persistent platelet reactivity has been associated with adverse vascular events. Light transmission aggregometry (LTA), the 'gold standard' for measuring the platelet response to aspirin therapy, is a cumbersome procedure and a simple and reliable alternative is required. Our aim was to explore whether serum thromboxane B2 (sTXB2) and soluble P-selectin can be used to identify patients who are at risk of increased platelet reactivity while on aspirin. METHODS AND RESULTS: We recruited 293 ischemic stroke patients, taking aspirin for more than seven days, and performed LTA to classify them. Based on therapeutic serum salicylate levels, 63 patients were excluded due to suspected non-compliance, followed by ELISA measurement of TXB2 and P-selectin in serum. Accordingly, patients were classified into 'Responders' (n = 122, 53%), 'Semi-responders' (n = 76, 33%) and 'Non-responders' (n=32, 14%) by LTA. Patients who had platelet aggregation of ≥70% with 10µM ADP and ≥20% with 0.5mM AA were defined as 'Non-responders'. In comparison with 'Responders', 'Non-responders' had 8.63-fold increased risk of secondary vascular events (p = 0.008). ROC curve analysis revealed that sTXB2, at a cut-off level of >4.15 ng/mL, could distinguish the patient group with elevated platelet reactivity with a sensitivity of 84.3% (AUC = 0.84), and was in fair agreement with the LTA-based classification of patients. Soluble P-selectin levels, on the other hand, had no discriminatory ability. CONCLUSION: We suggest sTXB2 measurement as an alternative to the LTA approach for identifying aspirin-treated ischemic stroke patients who are at risk of enhanced platelet reactivity and subsequent vascular events.