Indicator Of Platelet Activation Research Articles

The relation between aortic morphology and transcatheter aortic heart valve thrombosis: Particle tracing and platelet activation in larger aortic roots with and without neo-sinus

Transcatheter aortic heart valve thrombosis (THVT) affects long-term valve durability, transvalvular pressure gradient and leaflet mobility. In this study, we conduct high-fidelity fluid–structure interaction simulations to perform Lagrangian particle tracing in a generic model with larger aortic diameters (THVT model) with and without neo-sinus which is compared to a model of unaffected TAVI patients (control model). Platelet activation indices are computed for each particle to assess the risk of thrombus formation induced by high shear stresses followed by flow stagnation. Particle tracing indicates that fewer particles contribute to sinus washout of the THVT model with and without neo-sinus compared to the control model (−34.9%/−34.1%). Stagnating particles in the native sinus of the THVT model show higher platelet activation indices than for the control model (+39.6% without neo-sinus, +45.3% with neo-sinus). Highest activation indices are present for particles stagnating in the neo-sinus of the larger aorta representing THVT patients (+80.2% compared to control).This fluid–structure interaction (FSI) study suggests that larger aortas lead to less efficient sinus washout in combination with higher risk of platelet activation among stagnating particles, especially within the neo-sinus. This could explain (a) a higher occurrence of thrombus formation in transcatheter valves compared to surgical valves without neo-sinus and (b) the neo-sinus as the prevalent region for thrombi in TAV. Pre-procedural identification of larger aortic roots could contribute to better risk assessment of patients and improved selection of a patient-specific anti-coagulation therapy.

Soluble glycoprotein VI predicts abdominal aortic aneurysm growth rate and is a novel therapeutic target

AbstractA common feature in patients with abdominal aortic aneurysms (AAAs) is the formation of a nonocclusive intraluminal thrombus (ILT) in regions of aortic dilation. Platelets are known to maintain hemostasis and propagate thrombosis through several redundant activation mechanisms, yet the role of platelet activation in the pathogenesis of AAA-associated ILT is still poorly understood. Thus, we sought to investigate how platelet activation affects the pathogenesis of AAA. Using RNA sequencing, we identified that the platelet-associated transcripts are significantly enriched in the ILT compared with the adjacent aneurysm wall and healthy control aortas. We found that the platelet-specific receptor glycoprotein VI (GPVI) is among the top enriched genes in AAA ILT and is increased on the platelet surface of patients with AAAs. Examination of a specific indicator of platelet activity, soluble GPVI (sGPVI), in 2 independent cohorts of patients with AAAs is highly predictive of an AAA diagnosis and associates more strongly with aneurysm growth rate than D-dimer in humans. Finally, intervention with the anti-GPVI antibody (JAQ1) in mice with established aneurysms blunted the progression of AAA in 2 independent mouse models. In conclusion, we show that the levels of sGPVI in humans can predict a diagnosis of AAA and AAA growth rate, which may be critical in the identification of high-risk patients. We also identify GPVI as a novel platelet-specific AAA therapeutic target, with minimal risk of adverse bleeding complications, for which none currently exists.

Glycoprotein VI Platelet Receptor Blockade Attenuates Progression of Established Abdominal Aortic Aneurysms in Murine Models

Objective: Abdominal aortic aneurysms (AAA) frequently feature the formation of a nonocclusive intraluminal thrombus (ILT) along the site of aortic dilation. Platelets are known to maintain hemostasis and propagate thrombosis through several redundant activation mechanisms, yet the role of platelet activation in the pathogenesis of AAA associated ILT is still poorly understood. Thus, we sought to investigate how platelet activation via the glycoprotein VI receptor pathway impacts the pathogenesis of AAA. Methods and Results: RNA sequencing was performed on age-matched control human aortic tissue, AAA aortic tissue, and AAA ILT. Platelet transcripts comprised 25% of significantly enriched genes in the comparison of AAA thrombus to AAA tissue and control aortic wall, with GPVI increased by 9.1 Log2-FC (P = 3.21E−08). Circulating GPVI was significantly elevated in platelets isolated from AAA patients versus age-matched controls. Soluble GPVI (sGPVI—indicator of platelet activation), was significantly increased in the plasma of patients with fast-growing AAAs compared to slow-growing AAAs and healthy control subjects. To determine if GPVI blockade was protective from AAA progression, mice underwent either the angiotensin II (AngII) infusion or the topical elastase models of aneurysm formation. Following model initiation, aortic diameter was monitored by weekly ultrasounds. After two weeks, mice which developed an aneurysm (defined as an aortic diameter of >1.2mm) were randomized into control (IgG—50μg) or treatment (JAQ1—50μg, monoclonal GPVI antibody) groups. As expected, platelets isolated from JAQ1 treated mice did not activate in response to the GPVI specific agonist convulxin. Furthermore, JAQ1 treatment attenuated aneurysm progression, increased type I collagen deposition, attenuated macrophage accumulation, and increased survival in both murine AAA models versus IgG control treated mice. Conclusions: Platelets play a critical role in AAA pathophysiology and specific blockade of the GPVI-mediated activation pathway attenuates progression of established aneurysms in two independent murine models. Thus, our work demonstrates that specific targeting of GPVI to blunt platelet activation in AAA could be a potential therapeutic for a pathology with no current pharmacological treatments. R01HL147171-04 and R01HL158801-02. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Effect of semaglutide on global longitudinal strain and global myocardial work efficiency in patients with uncontrolled type 2 diabetes mellitus and obesity

Abstract Background Type 2 Diabetes mellitus (T2DM) increases of two-to three-fold the risk of cardiovascular disease (CVD). Cardiovascular outcome trials (CVOTs) demonstrated that glucagon-like peptide 1-receptor agonists (GLP1-RAs), as semaglutide in SUSTAIN-6 study, have effectively reduced CV risk in T2DM patients, so their use is recommended by guidelines. Purpose The objective of our work was to evaluate the effect of Semaglutide administration in a cohort of uncontrolled diabetic patients (within 5 years from diagnosis) on oxidative stress validated markers (8-isoprostane and NOX-2), platelet activation indicators (Sp-Selectin) and subclinical myocardial damage evaluated by measurement of deformation and efficiency parameters, obtained by speckle tracking echocardiography (STE). Methods We enrolled 70 Caucasian patients (mean age 65.5±8.2) with T2DM and obesity, 54 men and 16 women, 85.7% with hypertension, 14.2% with chronic obstructive pulmonary disease, 57.1% with sleep apnea syndrome, 18.5% with chronic kidney disease, and 41.4% with dyslipidemia. All patients were treated with statins and metformin, 42.8% with insulin, 24.2% with diuretics, 37.1% with ACE inhibitors, and 48.5% with angiotensin receptor antagonists. In the study the mean dose of semaglutide was 0.59±0.29 mg/week, no serious adverse events were reported. Results After 6 months of follow-up a significant improvement in fasting plasma glucose, insulinemia, HOMA, IGF-1, HbA1c and BMI (p<0.0001) was reported. In addition, there was a significant reduction in biomarkers of oxidative stress such as 8-isoprostane, Nox-2 and uric acid (p<0.0001), biomarkers of platelet activity such as Sp-Selectin and high-sensitivity C-reactive protein (hs-CRP) (p<0.0001). Moreover, we observed a significant improvement in left ventricular myocardial deformation parameters such as Global longitudinal strain (GLS) (p<0.0001) and global myocardial work efficiency (GWE) (p<0.0001). The linear correlation analysis showed that variation (Δ) GLS was inversely correlated with ΔHOMA (p=0.011), Δuric acid (p=0.025) and ΔSp-selectin (p<0.0001); ΔGWE was inversely correlated with ΔHOMA (p=0.011), Δuric acid (p=0.025) and ΔSp-selectin (p<0.0001). From stepwise multivariate linear regression model, ΔSp-selectin, ΔHOMA and Δuric acid justifying 27.8%(p<0.0001), 5.6%(p=0.010) and 4.4%(p=0.023) of ΔGLS variation, respectively. Instead ΔNOX-2, Δhs-CRP and ΔBMI justifying 22.3%(p<0.0001), 15.6%(p<0.0001), and 4.0%(p=0.022) of ΔGWE variation, respectively. Conclusion Treatment for 6 months with Semaglutide, in patients with uncontrolled T2DM and obesity, improved GLS and GWE. It’s plausible that this improvement may be justified by the reduction of inflammatory, oxidative stress and platelet activation parameters together with favorable metabolic changes; thus promoting coronary microcirculation protection with positive effects on myocardial contractility.

The Comparison of Soluble P-selectin, Anti-platelet Factor 4, and Platelet Maximum Aggregation Levels among Coronavirus Disease 2019 Patients

Abstract INTRODUCTION: The coronavirus disease 2019 (COVID-19) continues to have an enormous and extensive effect on global health, causing widespread devastation. Patients who have recovered from COVID-19 have an increased risk of thromboembolic disease. We suggest that soluble P-selectin and anti-platelet factor 4 (anti-PF4) plays a significant role in platelet activation, ultimately resulting in thrombosis. The purpose of this study is to compare the role of soluble P-selectin, anti-PF4, and platelet maximal aggregation levels in COVID-19 patients. MATERIALS AND METHODS: A cross-sectional study was conducted among COVID-19 patients who were admitted to the hospital between October 2021 and January 2022. RESULTS: From 160 individuals, we found that a number of individuals with older age (P = 0.014) and lower hemoglobin levels (P = 0.042) were significantly higher in the severe COVID-19 group compared to the nonsevere COVID-19 group. Remarkably, soluble P-selectin levels in mild-to-moderate COVID-19 were found to be significantly higher than the severe group, with statistical significance (P = 0.02). However, there was no significant difference in anti-PF4 levels between severe and nonsevere COVID-19 groups. Furthermore, platelet maximum aggregation was also significantly higher in the severe COVID-19 group than in the mild-to-moderate COVID-19 group by using 2.5 μM (P = 0.024), 5 μM (P = 0.026), and 10 mM adenosine-diphosphate (P = 0.02). CONCLUSION: Soluble P-selectin, an indicator of platelet activation, was shown to be significantly higher in mild-to-moderate COVID-19 group than the severe COVID-19 group. The maximum aggregation of platelets was also observed to be significantly greater in the severe COVID-19 group.

Effect of ticagrelor and clopidogrel dual antiplatelet therapy on MPVLR, MAADP, and AA inhibition rate in acute coronary syndrome patients after percutaneous coronary intervention.

To explore the effects of ticagrelor and clopidogrel dual antiplatelet therapy on the mean platelet volume-to-lymphocyte ratio (MPVLR), maximum amplitude of adenosine diphosphate-induced platelet-fibrin clots (MAADP), and arachidonic acid (AA) inhibition rates in patients with acute coronary syndrome (ACS) after percutaneous coronary intervention (PCI). A total of 120 patients with ACS undergoing elective PCI in our hospital between March 2020 and November 2021 were recruited. Patients were divided into 2 groups using the random number table method, with 60 patients in each group. The control group received clopidogrel + aspirin dual antiplatelet therapy, while the study group received ticagrelor + aspirin dual antiplatelet therapy. MPVLR, MAADP, and AA inhibition rates were compared between the 2 groups. Platelet activation indices, platelet micro PNA-223, and platelet gelsolin levels were measured before and 4 weeks after PCI. Changes in cardiac function indices, bleeding rates, and major adverse cardiovascular events (MACE) were compared between groups. The MAADP score of the study group was lower than that of the control group 3 days after surgery (P < .05). Compared with before surgery, CD62p, CD63, miR-223, PAC-1, platelet membrane glycoprotein IIb/IIIa complex, and gelsolin levels markedly decreased in both groups 4 weeks after surgery (P < .05). The platelet activation index and platelet miR-223 and gelsolin levels were significantly lower in the study group than in the control group 4 weeks after surgery (P < .05). The overall platelet inhibition effect was significantly better in the study group than in the control group (P < .05). Compared with before surgery, the left ventricular ejection fraction and stroke volume were significantly increased, and the left ventricular end-diastolic volume and left ventricular end-diastolic diameter significantly decreased in both groups 4 weeks after surgery (P < .05). No significant differences were found between the 2 groups in terms of the incidence of bleeding events or MACE (P > .05). Ticagrelor is more effective than clopidogrel for platelet inhibition after PCI in patients with ACS and is worthy of clinical recommendation.

Association between MPV and Cerebral Vascular Ischemic Burden in Mild to Moderate Alzheimer’s Disease

Title: Association between MPV and Cerebral Vascular Ischemic Burden in Mild to Moderate Alzheimers’s Disease &#x0D; Running Title: MPV and Ischemic Burden in AD &#x0D; ABSTRACT&#x0D; Objective: Vascular pathologies and chronic neuroinflammation play an important role in Alzheimer's Disease(AD). Increased platelet activity, which underlies the pathophysiology of atherosclerosis and systemic inflammation, has been reported several times in the setting of AD. However, the relationship between this increase and neuroimaging correlates has not been studied yet. This study aims to evaluate the relationship between mean platelet volume (MPV), as a reliable indicator of platelet activity, and vascular ischemic burden in neuroimaging of AD. Material- Method: Medical records of mild-moderate AD cases diagnosed in our dementia outpatient clinic between 2021-2022 were retrospectively reviewed. Patients were classified as having "mild" or "severe" vascular ischemic burden on MRI. Clinical findings and platelet markers were compared between the groups. Multivariate regression was applied for potential confounders regarding vascular ischemic burden. Results: Out of 59 patients, 36 had 'mild' and 23 had 'severe' ischemic burden. Demographic and clinical features were similar; however, MPV was significantly higher in the group with severe ischemia (p:0.013). Multivariate analysis revealed an independent association between MPV and ischemic burden. An MPV value of ≥8.7 fL had a sensitivity of 69.6% and a specificity of 61% for the presence of severe burden.&#x0D; Discussion: Our results highlight the role of platelet activation in the vascular pathogenesis of AD. During the early evaluation of AD, increased MPV can serve as a marker to determine the high-risk group in terms of cerebral ischemic burden. This might enable close monitoring and timely management of high-risk patients regarding the development of vascular morbidities. Keywords: Alzheimer's Disease, mean platelet volume, MPV, vascular ischemic burden, inflammation

Non-valvüler atriyal fibrilasyon hastalarında edoksaban tedavisi: Ortalama trombosit hacmi üzerinde paradoksal etki

Introduction: New generation oral anticoagulants (NOACs), which selectively and reversibly block the activity of clotting factor Xa, are now preferred as first-line therapy for preventing ischemic stroke in the treatment of atrial fibrillation (AF). Edoxaban, one of these NOACs, has been shown to be as effective as warfarin in preventing stroke or systemic embolism, while carrying a lower risk of bleeding and cardiovascular death. Mean platelet volume (MPV), as an indicator of platelet activity, is associated with an increased risk of ischemic stroke in patients with AF. Therefore, medical therapies that reduce MPV may play an important role in preventing unwanted ischemic events.&#x0D; &#x0D; Objective: The aim of this study is to determine whether edoxaban has an effect on platelet volume and other platelet indices, in addition to its protective anticoagulant effect against ischemic stroke.&#x0D; &#x0D; Materials and Methods: The study was designed as a retrospective cross-sectional study. Two hundred non-valvular AF patients without a history of oral anticoagulant use were included in the study. Complete blood count (CBC) and basic biochemical parameters (urea, creatinine, electrolytes, etc.) were recorded from the hospital registration system before edoxaban treatment was started, along with basic demographic data. The CBCs of the patients were reevaluated an average of 6 months (184 ± 9 days) after edoxaban treatment initiation, and platelet indices after edoxaban treatment were compared. Results were presented as mean ± standard deviation and percentage. Data were compared using Student's t-test and Wilcoxon test, and p

Is Mean Platelet Volume a Predictive Marker for the Development of Thrombosis in Patients with COVID-19 Infection?

Mean platelet volume (MPV) can provide important information about the course and prognosis of many diseases. MPV is an early indicator of platelet activation, which has an important role in the pathogenesis of thrombosis. In this study, we aimed to investigate whether MPV was a predictive marker for the development of thrombosis in hospitalized patients with COVID-19 infection. Fifty-seven patients whose courses were followed after the diagnosis of COVID-19 infection using a polymerase chain reaction test during the pandemic were included in the study. Our results demonstrated that there was a negative correlation between platelet count and MPV (r=0.470, p≤ 0.01), and there was a positive correlation between Platelet Distribution Width (PDW) and MPV (r=0,933, p≤ 0.01), but no significant correlation was found between the other variables and MPV.

Clinical significance of reactive thrombocytosis in the course of acute pancreatitis

BackgroundReactive thrombocytosis occurs secondary to systemic infections, inflammatory, and other conditions. The relationship between thrombocytosis and acute pancreatitis (AP) in inflammatory diseases is uncertain. This study aimed to evaluate the clinical significance of thrombocytosis in AP patients during hospitalization.MethodsSubjects within 48 h of AP onset were consecutively enrolled over 6 years. Platelet counts of ≥ 450,000/µL were defined as thrombocytosis, < 100,000/µL as thrombocytopenia, and other counts as normal. We compared clinical characteristics, including the rate of severe AP (SAP) assessed by the Japanese Severity Score; blood markers, including hematologic and inflammatory factors and pancreatic enzymes during hospitalization; and pancreatic complications and outcomes in the three groups.ResultsA total of 108 patients were enrolled. Although, SAP was more common in patients with thrombocytosis and thrombocytopenia (87.9% and 100%, respectively), the differences in lymphocytes and C-reactive protein, lactase dehydrogenase, and antithrombin levels, which are factors of the systemic inflammatory response, and the mean platelet volume, an indicator of platelet activation, were observed among patients with thrombocytosis and thrombocytopenia during hospitalization. Regarding pancreatic complications and outcomes, patients with thrombocytosis and thrombocytopenia had higher acute necrotic collection (ANC), pancreatic necrosis, intestinal paralysis, respiratory dysfunction, and pancreatic-related infection levels than patients with normal platelet levels. The relationship between pancreatic complications and thrombocytosis was assessed by multivariate logistic regression; the odds ratios for development of ANC, pancreatic necrosis and pancreatic-related infections were 7.360, 3.735 and 9.815, respectively.ConclusionsThrombocytosis during hospitalization for AP suggests development of local pancreatic complications and pancreatic-related infections.

Regulation of Mitochondria on Platelet Apoptosis and Activation

To explore the regulation of mitochondria on platelet apoptosis and activation, and the relationship between platelet apoptosis and activation. Platelets were isolated from peripheral venous blood of healthy volunteers. Cyclosporin A (CsA), which has a protective effect on the function of platelet mitochondria, BAPTA, which can chelate calcium ions across membranes in platelets, and NAC, an antioxidant that reduces the level of intracellular reactive oxygen species, were selected for coincubation with washed platelets, respectively. By flow cytometry, platelet aggregator was used to detect the changes of platelet mitochondrial function and platelet activation indexes after different interventions. H89, staurosporine, and A23187 led to platelet mitochondrial abnormalities, while CsA could effectively reverse the decline of platelet mitochondrial membrane potential caused by them. Antioxidant NAC could reverse platelet mitochondrial damage correspondingly, and completely reverse platelet shrinkage and phosphatidylserine eversion induced by H89. BAPTA, prostaglandin E1, acetylsalicylic acid and other inhibitors could not reverse the decline of platelet mitochondrial membrane potential. Mitochondrial function plays an important role in platelet apoptosis and activation. Abnormal mitochondrial function causes the imbalance of reduction/oxidation state in platelets, which leads to platelet apoptosis. Platelet apoptosis and activation are independent signal processes.

Mean Platelet Volume in Patients With Subclinical Hypothyroidism Attending at A Tertiary Care Hospital of Bangladesh

Background: Subclinical hypothyroidism (SCH) is a common endocrine disorder affecting about 3-8% of the general population. On the other hand, mean platelet volume (MPV) is an indicator of platelet activity, and elevated MPV is associated with adverse cardio-metabolic complications. This study was conducted to observe MPV in SCH and to correlate it with thyroid-stimulating hormone (TSH) and free thyroxine (FT4) levels. Materials and Methods: This cross-sectional observational study was conducted in Medicine and Endocrinology OPD of US- Bangla Medical College &amp; Hospital over twelve (12) months from September 2020 to August 2021. This study included forty (40) cases of newly detected SCH and twenty (20) age &amp; body mass index (BMI) matched euthyroid control subjects as per inclusion and exclusion criteria. Results: SCH group had higher TSH and MPV than controls (P value &lt;0.001 and &lt;0.05 respectively) where age, BMI, and FT4 level were comparable (P value&gt;0.05). MPV shows a positive correlation with BMI in SCH &amp; controls (P values &lt;0.05). MPV shows a significant positive correlation with TSH and a negative correlation with FT4 only in SCH (P&lt;0.05) but not in controls (P value&gt;0.05). Conclusion: Patients with SCH have elevated MPV, so they are at increased risk of developing an adverse cardiovascular outcome. J Dhaka Med Coll. 2022; 31(1) : 61-65

Overexpression of facilitative glucose transporter-3 and membrane procoagulation in maternal platelets of preeclamptic pregnancy

BackgroundPreeclampsia (PE) is a hypertensive disorder during pregnancy that results in significant adverse maternal and neonatal outcomes. Platelet activation is present in PE and contributes to the thrombo-hemorrhagic states of the disorder. However, the mechanisms that initiate and/or sustain platelet activation in PE are ill-defined. ObjectivesWe aimed to characterise this mechanism and the procoagulant potentials of platelets in PE. MethodsIn this quantitative observational study, we analyzed platelet procoagulant membrane dynamics in patients with PE (n = 21) compared with age-matched normotensive pregnancies (n = 20), gestational hypertension (n = 10), and non-pregnant female controls (n = 19). We analyzed fluorescently labeled indicators of platelet activation, bioenergetics, and procoagulation (phosphatidylserine exposure and thrombin generation), coupled with high-resolution imaging and thrombelastography. We then validated our findings using flow cytometry, immunoassays, classical pharmacology, and convolutional neural network analysis. ResultsPE platelets showed significant ultra-structural remodeling, are more extensively preactivated than in healthy pregnancies and can circulate as microaggregates. Preactivated platelets of PE externalized phosphatidylserine and thrombin formed on the platelet membranes. Platelets’ expression of facilitative glucose transporter-1 increased in all pregnant groups. However, PE platelets additionally overexpress glucose transporter-3 to enhance glucose uptake and sustain activation and secretion events. Although preeclampsia platelets exposed to subendothelial collagen showed incremental activation, the absolute hemostatic response to collagen was diminished, and likely contributed to greater blood loss perioperatively. ConclusionsWe revealed 2 bioenergetic mediators in the mechanism of sustained platelet procoagulation in preeclampsia. Although glucose transporter-1 and glucose transporter-3 remain elusive antiprocoagulant targets, they may be sensitive monitors of PE onset and progression.

Clinical value of the platelet and inflammatory factor activation in vascular endothelial injury in essential hypertension.

To investigate the clinical value of platelet and inflammatory factor activation in vascular endothelial injury in hypertension. A total of 120 hypertension patients diagnosed in our hospital from December 2019 to June 2021 were enrolled as study objects (Hypertension group); besides, another cohort of 60 healthy people undergoing physical examination at the same period were recruited as the controls (Control group). Next, the baseline clinical characteristics of subjects in the two groups were recorded and compared. Specifically, a hematology analyzer was adopt for detecting the mean platelet volume (MPV), platelet distribution width (PDW) and platelet hematocrit (PCT); ELISA for the level of IL-6, IL-8 and TNF-α; PHILIPS EPIQ 7 C (a device assessing endothelial vasodilator function in a non-invasive fashion) for reactive hyperemia index (RHI); univariate and multivariate regression analysis for risk factors triggering endothelial dysfunction; and Spearman correlation analysis for the correlation of platelet activation indicators and inflammatory factor level with vascular endothelial function. Compared with the Control group, the patients in the Hypertension group exhibited higher levels of MPV, PDW, PCT, inflammatory factors (IL-6, IL-8 and TNF-α) and lower RHI. Moreover, Spearman correlation analysis showed a significant negative correlation of MPV, PDW, PCT, IL-6, IL-8 and TNF-α level with RHI level. In addition, univariate and multivariate regression analysis presented that MPV, PCT, IL-8 and TNF-α were risk factors for vascular endothelial dysfunction. The activation of platelet and inflammatory factor is closely related to vascular endothelial function injury in patients with hypertension. To be specifically, platelet and inflammatory factor activation can effectively reflect the vascular endothelial function injury in patients with hypertension and has high clinical value.

Aluminum Nanoparticles Affect Human Platelet Function In Vitro.

Endoprostheses are prone to tribological wear and biological processes that lead to the release of particles, including aluminum nanoparticles (Al NPs). Those particles can diffuse into circulation. However, the toxic effects of NPs on platelets have not been comprehensively analyzed. The aim of our work was to investigate the impact of Al NPs on human platelet function using a novel quartz crystal microbalance with dissipation (QCM-D) methodology. Moreover, a suite of assays, including light transmission aggregometry, flow cytometry, optical microscopy and transmission electron microscopy, were utilized. All Al NPs caused a significant increase in dissipation (D) and frequency (F), indicating platelet aggregation even at the lowest tested concentration (0.5 µg/mL), except for the largest (80 nm) Al NPs. A size-dependent effect on platelet aggregation was observed for the 5-20 nm NPs and the 30-50 nm NPs, with the larger Al NPs causing smaller increases in D and F; however, this was not observed for the 20-30 nm NPs. In conclusion, our study showed that small (5-50 nm) Al NPs caused platelet aggregation, and larger (80 nm) caused a bridging-penetrating effect in entering platelets, resulting in the formation of heterologous platelet-Al NPs structures. Therefore, physicians should consider monitoring NP serum levels and platelet activation indices in patients with orthopedic implants.

EVALUATION OF SERUM SCUBE-1 LEVELS AND AFFECTING FACTORS IN SMOKERS

Aim: Serum signal peptide-CUB-EGF domain-containing protein-1 (SCUBE-1), an indicator of platelet activation, is a biochemical marker used to evaluate the risk for cardiovascular diseases. This study aimed to evaluate the alteration of plasma levels of SCUBE-1 in smokers compared to healthy controls and determine the affecting factors.&#x0D; Materials and Methods: This prospective study was designed as an experimental, single-centered study with a control group. The study included smokers aged 18-65 years who were admitted to the Smoking Cessation Clinic of a tertiary hospital and a control group consisting of healthy volunteers admitted to the Family Medicine Outpatient Clinic and had never smoked. Sociodemographic data of all participants and smoking histories and addiction levels of smokers were questioned. Exhaled carbon monoxide (CO) levels were measured. Plasma SCUBE-1 levels were studied and compared from samples obtained from venous blood. &#x0D; Results: A total of 82 individuals, consisting of the "smoker" patient group (n=44) and the "non-smoker" control group (n=38), were included in the study. While the mean SCUBE-1 value was 1.28±0.70 ng/ml in smokers, it was 1.54±1.09 ng/ml in non-smokers. There was no statistical difference between smokers and non-smokers in terms of SCUBE-1 (p=0.500). There was no statistically significant correlation between SCUBE-1 levels and exhaled CO level, smoking characteristics and addiction levels in smokers. &#x0D; Conclusion: Our study showed that the plasma SCUBE-1 value in smokers did not increase at statistically significant levels compared to the control group. Therefore, it was concluded that it would not be useful in evaluating the risk of cardiovascular diseases and the susceptibility to thrombosis.

The change of mean platelet volume and mean platelet volume to platelet count ratio one year after iniation of peritoneal dialysis

Aim: Cardiovascular diseases are the most common cause of mortality in patients undergoing peritoneal dialysis. Thrombocyte indices which are indicators of platelet activation are predictors of cardiovascular events. We aim to examine the change in platelet count, mean platelet volume, and mean platelet volume to platelet count ratio one year after initiation of peritoneal dialysis in patients with end-stage renal disease. Materials and Methods: This retrospective study included 28 patients. Demographic and clinical characteristics of the patients at the time of initiation of peritoneal dialysis were recorded from the patient files. Laboratory data within the last month before the initiation of peritoneal dialysis and in the first year were recorded from the patient files. The mean platelet volume to platelet count ratio was calculated as mean platelet volume (femtolitres) divided by platelet count (number of thousand platelets/microliter). Results: The mean age was 51.1 ± 14.6 years, and 42.8% of the patients were male. Diabetic nephropathy and hypertensive nephropathy were the most common causes of end-stage renal disease. One year after the initiation of peritoneal dialysis, the urea level decreased significantly, and C-reactive protein level increased significantly. Platelet count increased from 240 ± 55 x10 3 /μL to 274 ± 53 x10 3 /μL (p=0.003) and mean platelet volume decreased from 10.7 ± 1.0 fl to 10.2 ± 0.8 fl (p

Relationship between platelet mass index and postoperative atrial fibrillation after elective coronary artery bypass surgery: aretrospective study.

Atrial fibrillation (AF) is the most common complication after cardiac surgery. The pathogenesis of postoperative atrial fibrillation (POAF) is multifactorial and one of the known factors is inflammation. Platelet mass index (PMI) is an indicator of platelet activation and abetter inflammatory marker than mean platelet volume (MPV). In this retrospective study, we investigated the relationship between POAF and PMI. The study included 848 consecutive patients (655male and 193female) who had elective isolated coronary artery by-pass grafting (CABG) or combined CABG and valvular surgery. Platelet count and MPV were measured from preoperative blood samples to calculate PMI. Post-operative atrial fibrillation was defined as irregular and fibrillatory Pwaves occurring 48-96 h after cardiac surgery and lasting at least 30 s. The PMI values in patients who developed POAF were compared with those in patients who did not develop POAF. Patients who developed POAF had higher PMI values (2549.3 ± 1077.1) when compared with patients in sinus rhythm (2248.1 ± 683.4; p < 0.01). In multivariate regression analysis, age (OR: 1.05; 95%CI: 1.02-1.09; p = 0.01), left atrial diameter (OR: 1.05; 95% CI: 1.03-1.09; p = 0.02), hs-CRP (OR: 1.09; 95%CI: 1.05-1.13; p < 0.01), EuroSCOREII (OR: 1.27; 95% CI: 1.14-1.41; p < 0.01), and PMI (OR: 1.01; 95% CI: 1.001-1.02; p < 0.01) were independent predictors of POAF. In ROC analysis, PMI ≥ 2286 predicted POAF development with asensitivity of 69% and aspecificity of 58% (AUC: 0.66; p < 0.01) CONCLUSION: Asignificant relationship was found between preoperatively calculated PMI and POAF. We showed that PMI may be used to predict patients who are at high risk of developing POAF.

Heparin-induced thrombocytopenia: effect of heat inactivation of patient's serum on functional flow cytometric assay results.

Heat inactivation of a patient's sample is not systematically performed in the diagnostics of heparin-induced thrombocytopenia (HIT). Some authors recommend that the patient's sample is heat-inactivated to avoid the effect of thrombin on platelet activation in a functional assay. Others do not find this additional step essential or even advise against it. An enzyme-linked immunosorbent assay (ELISA) and flow cytometry-based functional assay with CD62P as a marker of platelet activation were performed. Forty-seven patients with suspected HIT and three healthy controls were included in the study. Each serum sample was divided into two aliquots: one was heat-inactivated and the other was not. Both aliquots were tested in parallel using the same donor platelets from four randomly selected individuals. We designed an index of platelet activation for both protocols to assess platelet activation in the assay and to compare the results. We observed a higher percentage of platelet activation in heat-inactivated compared to non-heat-inactivated sera. This phenomenon was seen in low and high heparin steps, although it did not occur for all samples. There were discrepant results in seven samples, which tested negative in the non-heat-inactivated protocol and positive in the heat-inactivated protocol. There was no case in which the result of a non-heat-inactivated aliquot was positive and the corresponding heat-inactivated aliquot was negative. Due to the higher percentages of donor platelet activation, all seven non-compliant cases met our current criteria for a positive result. However, those results were probably false-positive based on ELISA optical density value and 4T score. Therefore, in the current settings, heat inactivation of serum is not suitable for our flow cytometric functional assay since it can cause an elevated risk of creating false-positive results.

HMGB1-activatied NLRP3 inflammasome induces thrombocytopenia in heatstroke rat.

BackgroundThrombocytopenia, an early common complication in heatstroke (HS), has been widely considered as a mortality predictor of HS. The mechanism underlying thrombocytopenia in HS remains unknown. It is not known whether NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome is activated in HS platelet, which, in turn, induces platelet activation and thrombocytopenia. This study tried to clarify the activation of the NOD-like receptor signaling pathway under HS conditions and investigate its roles in mediating HS-induced thrombocytopenia.MethodsRat HS models were established in a certain ambient temperature and humidity. Platelets, isolated from blood, were counted and CD62P, an index of platelet activation, was measured by flow cytometry in all rats. The colocalization of NLRP3 inflammasome in platelet was detected by confocal fluorescence microscopy. Mitochondrial-derived reactive oxygen species (ROS) was detected using the molecular probes. Plasma HMGB1 and IL-1β levels were measured by ELISA.ResultsPlatelet activation, showed by upregulated CD62P, and thrombocytopenia were observed in HS rats. HS activated the NLRP3 inflammasome, which was induced by elevated levels of ROS, while the upregulated CD62P and thrombocytopenia triggered by NLRP3 inflammasome were attributed to the high mobility group box protein 1 (HMGB1) inplasma. Moreover, inhibition of the NOD-like receptor signaling pathway in rats with HS suppressed platelet activation and the decline of platelet count. Similar results were obtained when the receptor toll-like receptor 4 (TLR4)/advanced glycation end product (RAGE) was blocked.ConclusionsThe NOD-like receptor signaling pathway induces platelet activation and thrombocytopenia in HS rats. These findings suggested that the NLRP3 inflammasome might be the potential target for HS treatment.