Platelet Activation In Patients Research Articles

Blood clot properties, thrombin generation and platelet activation in patients with dysglycemia and established atherosclerotic cardiovascular disease: The CASCARA study.

Blood clot properties, thrombin generation and platelet activation in patients with dysglycemia and established atherosclerotic cardiovascular disease: The CASCARA study.

Prospects for the pharmacological validation of the use of platelets as a “peripheral model” of neurons

Depressive disorders often occur in patients with cardiovascular pathologies and are a predictor of the development of thrombotic events, such as myocardial infarction, acute ischemic cerebrovascular accident, and pulmonary embolism. These are believed to be caused by the structural and biochemical relationship between platelets and brain neurons, which allows us to consider platelets as a marker of central nervous system (CNS) pathologies. This review aimed to assess the relationship between the hemostasis system and the development of depressive disorders using platelets as a “peripheral model” of neurons and evaluate the effectiveness of drugs for the treatment of depression. The study was conducted in accordance with the recommendations of Preferred Reporting Items for Systematic Reviews and Meta-Analyses. A systematic literature search was conducted using PubMed, Cochrane, and CINAHL databases from 2018 to 2023, according to the following keywords: “hemostasis,” “acute cerebrovascular accident,” “depression,” “depressive disorders,” “platelets,” “cardiovascular diseases.” The data obtained indicate both a clinical link between depressive disorders and vascular events and the commonality of platelets and CNS cells because of the commonality of the following proteins: transporters and receptors of serotonin or 5-hydroxytryptamine, amyloid precursor protein, and brain neurotrophic factor, which were previously considered specific neural proteins. In addition, a relationship exists between hemostasis dynamics and drug therapy for depression. In this review, changes in hemostasis in terms of platelet activation in patients with depression and vascular disease were critically analyzed. The literature presents diverse mechanisms of platelet induction, which require further study. A rational study of the pathways of platelet activation in patients with depressive disorders will provide a comprehensive understanding of the molecular mechanisms underlying the relationship between hemostasis and depression in various vascular pathologies. Platelet activation in patients with depression and the dynamics of changes in hemostasis parameters during the treatment of depressive disorders allow us to consider hemostasis as a peripheral marker of the CNS and pharmacotherapy.

Comparison of platelet activation in patients undergoing coronary bypass surgery with conventional and mini extracorporeal systems

Aim: The aim of this study was to compare platelet activation in patients undergoing coronary bypass surgery with conventional and mini extracorporeal systems. Material and Methods: Our study is a retrospective study and a total of 116 patient data were obtained. Patients were divided into two groups as conventional extracorporeal and mini extracorporeal system bypass patients. Equal numbers of patients (n=58) were included in both groups. The data of patients who underwent coronary bypass surgery with conventional and mini extracorporeal systems between January 2022 and December 2022 were included in the study. Results: In our study, no significant difference was found between patients bypassed with conventional and mini extracorporeal system in terms of pump time and cross-clamp time. Although the duration of intensive care unit stay and total hospitalization were found to be shorter in patients bypassed with the mini-extracorporeal (MECC) system than those bypassed with the conventional method, the difference between the groups was not significant. As a result of our study, it was observed that postoperative ejection fraction (EF) values significantly increased and hematocrite (HTC), hemoglobin (Hb), platelet (PLT) and procalcitonin (PCT) values significantly decreased in both groups of patients who underwent bypass with conventional and MECC system, and no significant difference was found between pre- and postoperative mean platelet volume (MPV) and platelet distribution width (PDW) values. As a result of our study, postoperative PLT and PCT values in the MECC group were found to be significantly higher than those in patients who underwent bypass with the conventional method. Conclusion: Considering the results obtained in our study, it is seen that the values in patients bypassed with the MECC system are more favorable than those bypassed with the standard method, but more studies on the subject are needed.

Single-cell transcriptomics of the immune system in ME/CFS at baseline and following symptom provocation

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a serious and poorly understood disease. To understand immune dysregulation in ME/CFS, we use single-cell RNA sequencing (scRNA-seq) to examine immune cells in patient and control cohorts. Postexertional malaise (PEM), an exacerbation of symptoms following strenuous exercise, is a characteristic symptom of ME/CFS. To detect changes coincident with PEM, we applied scRNA-seq on the same cohorts following exercise. At baseline, ME/CFS patients display classical monocyte dysregulation suggestive of inappropriate differentiation and migration to tissue. We identify both diseased and more normal monocytes within patients, and the fraction of diseased cells correlates with disease severity. Comparing the transcriptome at baseline and postexercise challenge, we discover patterns indicative of improper platelet activation in patients, with minimal changes elsewhere in the immune system. Taken together, these data identify immunological defects present at baseline in patients and an additional layer of dysregulation in platelets.

Prolonged platelet hyperactivity after COVID-19 infection.

Platelet hyperactivity often occurs in patients with coronavirus disease 2019 (COVID-19). However, it remains unclear how long platelet hyperactivity lasts after the acute phase, owing to a lack of follow-up studies. To elucidate the course of platelet hyperactivity, we serially measured platelet activity in patients with COVID-19 up to 40 days after hospital admission using an easily assessable haematology analyser that semi-quantitates platelet clumps on a scattergram. Our results showed that platelet hyperactivity persisted for at least 40 days even after acute inflammation subsided in most patients with COVID-19, regardless of disease severity. Persistent platelet hyperactivity may contribute to thromboembolic complications in post-COVID-19 patients.

The LIPL study: Postprandial lipid profile, inflammation, and platelet activity in patients with chronic coronary syndrome

Background and aimsIt is suggested that the changes in atherosclerosis happen mainly under the influence of non-fasting lipids. To date, the studies in the postprandial state were primarily performed on healthy subjects. This exploratory, cross-sectional study investigates the change in lipid profile, inflammation, and platelet activation in patients with different cardiovascular risk profiles in the postprandial state. MethodsThe studied population consists of 66 patients with different cardiovascular risks: patients with a history of the chronic coronary syndrome (CCS) and diabetes mellitus type 2 (DM2) (n = 20), CCS without DM2 (n = 25), and a healthy control group (n = 21). Lipid variables and markers of platelet function and inflammation were assessed during the fasting state and three and 5 h after a standardized fat meal using a standardized oral fat tolerance test (OFTT), a milkshake with 90 g of fat. ResultsPatients with CCS and DM2 were significantly older and had the highest BMI. All patients with CCS were on acetylsalicylic acid, and 95% of CCS patients were on high-dose statins. The absolute leukocyte and neutrophile count increased significantly in the control group during the OFTT in comparison to CCS subjects. There was a significant decrease of HDL and increase of triglycerides during the OFTT, however with no difference between groups. There was no difference in the change of platelet activity between all groups. ConclusionThis study showed that OFTT leads to an increased postprandial inflammation response in healthy group compared to CCS ± DM2 while there was no change in lipid profile and platelet activity.

New Insights into the Role of HMGB2 in ST-Segment Elevation Myocardial Infarction.

Ischemic heart disease is one of the leading causes of death in the world, of which ST-segment elevation myocardial infarction (STEMI) is an important type. Inappropriate activation and accumulation of platelets typically induced thrombosis, which may result in acute vessel occlusion and STEMI. Multiple cytokines have been shown to regulate platelet activation, but the relationship between HMGB2 and platelet activation has not been elucidated. We collected peripheral blood of STEMI patients and healthy adults, and mass spectrometry analysis of platelet proteins was conducted. The "edgeR" package was used to identify the differentially expressed proteins (DEPs). The Kyoto Encyclopedia of Genes and Genomes (KEGG), Gene ontology (GO) and Gene Set Enrichment Analysis (GSEA) were used to identify the significantly changed pathways. Western blot and ELISA were used to detect the expression of a high mobility group box 2 (HMGB2). Flow cytometric analysis and platelet aggregation rate were performed to evaluate the activation of platelets. We identified ALOX5, HIST1H1B, S100A11, HMGB2, and RPS15A were the top five up-regulated proteins by differential expression analysis. Western blot verified that the relative protein expression of HMGB2 in platelet was significantly higher in STEMI patients compared with control adults, and the results of ELISA indicated that the serum HMGB2 level increased and significantly correlated with neutrophil count in STEMI patients. Further investigation showed that the platelet aggregation induced by ADP, the activation of integrin αIIbβ3 and CD62P expression on platelet surface were all enhanced by the recombinant HMGB2 (rHMGB2). In conclusion, HMGB2 may be the key molecule to regulate platelet activation in patients with STEMI, which may serve as a potential therapeutic target for STEMI.

Refractory kaposiform lymphangiomatosis relieved by splenectomy.

Kaposiform lymphangiomatosis (KLA) is a rare and complex lymphatic anomaly with a poor prognosis. There is no standard treatment, and drug therapies are the most common therapeutic method. However, some patients' symptoms become gradually aggravated despite medical treatment. Splenectomy may be an alternative option when pharmacological therapies are ineffective. We reviewed and evaluated the cases of 3 patients with KLA who ultimately underwent splenectomy. Results: The lesions were diffusely distributed and involved the lungs and spleens of the 3 patients. Laboratory examinations revealed that all three patients had thrombocytopenia and reduced fibrinogen levels. All patients underwent symptomatic splenectomy after the medication failed. Surprisingly, their symptoms greatly improved. Histopathological investigation of the splenic lesions of the three patients confirmed the diagnosis of KLA. Immunohistochemical staining showed positivity for CD31, CD34, podoplanin, Prox-1 and angiopoietin 2 (Ang-2). This study aimed to review the features of KLA patients treated by splenectomy and explore the underlying link between splenectomy and prognosis. The reason for the improvement after splenectomy may be related to increased Ang-2 levels and platelet activation in patients with KLA. Future research should seek to develop more targeted drugs based on molecular findings, which may give new hope for the treatment of KLA.

Characteristics of changes in the functional activity of platelets in patients with ACS using different regimes of antiplatelet treatment

Characteristics of changes in the functional activity of platelets in patients with ACS using different regimes of antiplatelet treatment

Gender differences in serum markers of inflammation and platelet activation in patients with non-valvular atrial fibrillation

The prevalence of atrial fibrillation is high and comparable in both sexes. Such factors as differently expressed blood biomarkers in women and men may play a role in the occurrence of atrial fibrillation and the development of thrombotic complications. To study markers of inflammation and platelet activation in patients with atrial fibrillation of non-valvular origin, receiving anticoagulant therapy and having a history of thrombotic complications and patients with atrial fibrillation without thrombotic complications, depending on the gender of the patients. The study included 22 healthy volunteers and 60 patients diagnosed with atrial fibrillation receiving anticoagulant therapy, of which 21 patients developed thrombotic complications. Serum levels of α2- macroglobulin, hsC-reactive protein, fetuin A, α-1-acid glycoprotein, L-selectin, serum amyloid P, adipsin, and platelet factor 4 were studied on FLEXMAP 3D using Acute Phase diagnostic test systems Panel 3. A comparative study of the content of biomarkers demonstrated an increased concentration of C-reactive protein in men and women in both groups of patients with atrial fibrillation; decrease in fetuin A and L-selectin in the group of women with thrombosis compared with women without thrombotic complications and compared with healthy women. There were no gender differences in the concentration of fetuin A and L-selectin in the group of patients with atrial fibrillation without thrombotic complications and in healthy volunteers. The level of adipsin had no gender differences in the group of patients with atrial fibrillation with thrombosis and in healthy volunteers, however, it was significantly increased in women without thrombosis. The content of platelet factor 4 in women in both groups of patients exceeded the value of this indicator in healthy women; no gender differences were found in the groups of patients with atrial fibrillation. Low levels of fetuin A and L-selectin, with a simultaneous increase in C-reactive protein and platelet factor 4, lead to an increase of prothrombogenic potential and to a change in the balance of pro- and antiinflammatory mediators towards increased inflammation in female patients with atrial fibrillation.

The LIPL Study Postprandial lipid profile, inflammation and platelet activity in patients with chronic coronary syndrome

Abstract Funding Acknowledgements Type of funding sources: None. Introduction In general, most people spend their day in a non-fasting state. Hence, it is suggested that the changes in atherosclerosis happen mainly under the influence of non-fasting lipids. Up to date, the studies in the postprandial state were primarily performed on healthy subjects. Aim This exploratory, cross-sectional study investigates the change in lipid profile, in biomarkers of inflammation, as well as markers of platelet activation in patients with different cardiovascular risk profiles in the postprandial state. Methods The studied population consists of 66 patients with different cardiovascular risk: patients with a history of chronic coronary syndrome (CCS) and diabetes mellitus type 2 (DM2) (n=20), CCS without DM2 (n=25), and a healthy control group (n=21). Lipid variables and markers of platelet function were assessed during the fasting state (baseline) and three and five hours after a standardized fat meal using a standardized oral fat tolerance test (OFTT), a milkshake with 90g of fat. Platelet activity was measured with the Multiplate Assay using adenosine diphosphate (ADP), arachidonic acid (ASPI) and thrombin-receptor activating peptide (TRAP) as stimulants. Results Patients with CCS and DM2 were significantly older and had the highest BMI. All patients with CCS were on acetylsalicylic acid, and 95% of CCS patients were on high-dose statins. HDL-c decreased significantly during the OFTT, with a peak after five hours (3.46±0.4 mg/dL, p<0.001). Triglycerides (TG) increased significantly during the OFTT, with a peak after five hours (130.2 ± 14.5 mg/dL, p<0.001) irrespective of the group. All other variables of the lipid profile remained stable during the OFTT. The absolute leucocyte and neutrophile count and the neutrophile to lymphocyte ratio (NLR) increased significantly during the OFTT in the whole study population, whereas the absolute lymphocyte count increased significantly only in the control group. A significant increase in platelet activity during OFTT was shown in the control group by the increased absolute platelet count, increased reticulated thrombocytes, and increased platelet reactivity measured by the ASPI and TRAP tests, respectively. There was no significant change in the markers of platelet activity during the OFTT in patients with CCS with/without DM2. Conclusion This study showed that a standardized fatty meal changes HDL-c and TG concentrations and leads to an increased postprandial inflammation response irrespective of the cardiovascular risk and to increased platelet activity in healthy subjects, while there was no increase in platelet activity in higher-risk CCS patients.

Single-cell analysis of platelets from patients with periodontitis and diabetes

BackgroundBlood platelets are known to play a role in the development of atherosclerotic disease, thrombi, and hemostasis. Investigation of blood platelet transcriptome could provide evidence of disorders that increase vulnerability to cardiovascular disease. However, research on the molecular insights of platelet activation in patients with periodontitis and patients with periodontitis and type 2 diabetes mellitus (DM) is still lacking. ObjectivesIn this study, we analyzed expression in blood platelets from patients with periodontitis and patients with concurrent periodontitis and DM to examine the transcriptomic profile of platelets induced by periodontitis and the modifying effects of DM. MethodsWe obtained the transcriptional profiles of blood platelets from 11 healthy donors, 10 patients with periodontitis, and 6 patients with periodontitis and DM using single-cell RNA sequencing. The biological processes and coexpressed modules of transcriptionally altered genes were further explored. ResultsBoth the patients with periodontitis and DM and those with periodontitis without DM showed higher levels of platelet activation and coagulation signals than the healthy individuals. Platelets from the patients with periodontitis had higher expression levels of genes for RHO GTPase effectors, whereas platelets from the patients with periodontitis and DM demonstrated higher expression of genes involved in oxidative phosphorylation and cellular responses to stress than those from the controls. However, compared with the patients with only periodontitis, those with periodontitis and DM presented a lower expression level of genes for hemostasis and platelet receptors. ConclusionThese results suggest that periodontitis contributes to establishment of blood coagulation via platelet dysregulation, whereas the comorbidities of patients with periodontitis and DM impair the components of platelets, thus preventing normal functions.

Association of High Mobility Group Box-Protein 1 and Platelet Microparticles in Patients After Hematopoietic Stem Cell Transplantation.

Thrombotic complications after allogeneic hematopoietic stem cell transplantation (allo-HSCT) significantly impact transplant outcomes. We focused on high mobility group box-protein (HMGB)1, one causative agent of thrombotic lesions in allo-HSCT, and investigated its association with platelets. We statistically analyzed available data from 172 patients with hematopoietic malignancies receiving allo-HSCT. A significant enhancement of monocyte-chemotactant protein-1, HMGB1, and platelet-derived microparticle (PDMP) levels was observed at day 0 after transplantation as compared to pre-transplantation. Multivariate analysis of the association among HMGB1 and 16 factors on day 0 revealed a significant correlation of HMGB1 levels with thrombin-antithrombin complex, interleukin-6, and PDMPs. High mobility group box-protein 1-induced procoagulant platelet induction and PDMP generation were performed in vitro using healthy platelets. High mobility group box-protein 1-induced PDMP generation was suppressed by toll-like receptor inhibitors and recombinant thrombomodulin. These results suggest that HMGB1 contributes to platelet activation in patients after allo-HSCT and is associated with PDMP-related thrombotic complications.

Significance of Some Markers of Systemic Inflammation and Platelet Activation in Patients with Type 2 Diabetes Mellitus in the Enugu State University of Science and Technology Teaching Hospital Enugu State Nigeria

Diabetes mellitus has over the years become a public health challenge and a complex disease which is characterized by chronic hyperglycemia that results in microvascular and macro vascular complications.

Translational insights into mechanisms underlying residual venous obstruction and the role of factor XI, P-selectin and GPVI in recurrent venous thromboembolism

BackgroundResidual venous obstruction (RVO) after deep vein thrombosis (DVT) is considered a risk factor of recurrent venous thromboembolism (VTE), arterial events and post-thrombotic syndrome (PTS). We hypothesized thrombo-inflammatory markers might be associated with RVO and clinical outcomes. Materials and methodsIn a DVT cohort with routine RVO-assessment and 5-year follow-up, patients were invited for blood withdrawal after stopping anticoagulants. Thrombin generation potential, coagulation enzyme:inhibitor complexes, soluble platelet markers and clinical markers were measured in platelet-poor plasma. Associations were represented as odds ratio (OR) or hazard ratio (HR) per standard deviation. ResultsPatients with RVO (102/306, 33 %) had higher rates of PTS (24 vs. 12 %, p = 0.008), but similar rates of recurrence (16 vs. 15 %, p = 0.91) and arterial events (7 vs. 4 %, p = 0.26). RVO was associated with thrombin peak height (OR 1.40 [1.04–1.88]), endogenous thrombin potential (ETP, OR 1.35 [1.02–1.79]), and CRP (OR 1.74 [1.10–2.75]). Recurrent VTE was associated with ETP (HR 1.36 [1.03–1.81]), FXIa:C1-inhibitor (HR 1.34 [1.04–1.72]), thrombin:antithrombin (HR 1.36 [1.16–1.59]), soluble P-selectin (HR 2.30 [1.69–3.11]), soluble glycoprotein VI (sGPVI, HR 1.30 [1.01–1.69]), D-dimer (HR 1.56 [1.31–1.86]), and factor VIII (HR 1.44 [1.15–1.82]). Arterial events were associated with sGPVI (HR 1.80 [1.25–2.59]). PTS was not associated with any marker. ConclusionsOur findings indicate RVO was associated with thrombo-inflammation, but this did not predict clinical outcomes in this setting. Importantly, we found recurrent VTE was associated with ongoing coagulation and platelet activation in patients well beyond the acute phase of DVT. Furthermore, sGPVI indicated an increased risk of arterial events, highlighting the role of platelets in arterial thrombosis following DVT.

Platelet CD36 links overweight and a prothrombotic phenotype in patients with non-valvular atrial fibrillation.

The pathophysiological mechanisms linking the overweight and prothrombotic state of non-valvular atrial fibrillation (NVAF) are incompletely understood. Our objective was to evaluate the effect of platelet CD36 on the risk of stroke associated with overweight in NVAF patients. A cross-sectional study enrolled 182 subjects with NVAF in two groups: normal weight (18.5 < body mass index(BMI) < 25.0 kg/m2) and overweight (BMI ≥ 25.0 kg/m2). Clinical data, medical history, vital signs, transthoracic echocardiography parameters, and medication were recorded. Biochemical characteristics including blood glucose and serum lipid were analyzed in the Laboratory. The expression of platelet CD36 and integrin αIIbβ3 was detected by flow cytometry. Among the 182 patients with NVAF, 68 (37.36%) were classified as normal weight, 114 (62.64%) as overweight. With an increase in BMI, waist-hip ratio, cholesterol, triglycerides, left atrium diameters, and the ratio of mitral inflow E velocity to myocardial e' velocity in the mitral annulus (E/e') increased significantly (P < 0.05). The mean fluorescent intensity of platelet CD36 increased significantly in overweight patients (P < 0.01), in line with platelet activation biomarkers (platelet integrin αIIbβ3). Platelet CD36 was positively correlated with BMI and platelet integrin αIIbβ3, respectively (P < 0.05). Additionally, platelet CD36 and BMI were independent risk factors for platelet activation in patients with NVAF. Platelet CD36 is speculated to mediate the complex crosstalk between overweight and platelet hyperactivity, leading to the prothrombotic state in overweight patients with NVAF. Platelet CD36 could be a potential target for preventing the prothrombotic state in overweight patients with NVAF.

Evaluation Of Platelet Aggregation Activity Depending on The Duration of Antiplatelet Administration in Patients with Coronary Heart Disease

To study the aggregation activity of platelets in patients with ischemic heart disease depending on the long-term intake of acetylsalicylic acid (ASA). Material and methods. The study included: 116 patients with coronary artery disease with stable angina pectoris, taking a standard dose of aspirin 75 mg/day. during various terms. Patients with SSN were divided into 4 groups according to the duration of taking ASA. Platelet aggregation was measured using a laser platelet aggregation analyzer Alat-2 Biol, with computer processing according to the AGGR program. Adenosine diphosphate (ADP) in concentrations of 0.1, 1.0, 5.0 mmol/l was used as an inductor. The results of the study of patients taking ASA for more than 5 years showed that spontaneous aggregation and ADP-induced platelet aggregation were higher than in patients taking the drug for less than 5 years. Statistically significant differences were observed when compared with a group of patients taking ASA for less than a year (spontaneous aggregation of 1.7±0.09 (p&lt;0.05), 0.1 μm ADP-induced aggregation of 6.58±0.86 (p&lt;0.05), 1.0 μm ADP-induced aggregation of 16.51±1.63 (p&lt;0.01), 5.0 μm ADP-induced aggregation 58.44±3.72 (p&lt;0.01). Conclusion. Thus, the results showed that with an increase in the duration of aspirin intake, there was a change in both spontaneous and ADP-induced platelet aggregation with a statistically significant increase.

Proprotein convertase subtilisin/kexin type 9 (PCSK9), platelet activation and interaction with the vascular endothelium: the impact of PCSK9 inhibition with evolocumab in acute coronary syndrome

Abstract Background/Introduction Platelet activation and endothelial dysfunction may contribute to adverse outcomes in patients with acute myocardial infarction. Pre-clinical studies indicate PCSK9 enhances platelet activation. Purpose Our goals were (1) to examine the role of PCSK9 as a potential mediator of platelet activation in patients with acute coronary syndrome (ACS) and (2) to perform immunohistochemical studies of left internal mammary artery (LIMA) specimens to examine interactions among PCSK9, platelets, and endothelial cells in specimens obtained during coronary bypass surgery. Methods Participants from the Evolocumab in Acute Coronary Syndrome trials (EVACS; NCT03515304, NCT04082442), with a NSTEMI and a troponin-I of &amp;gt;5 ng/ml or a STEMI were randomized to placebo or to 420 mg SC of evolocumab, a monoclonal anti-PCSK9 antibody, within 24 hours of hospitalization. We performed serial ex vivo analysis of PF4, a marker of platelet activation, in serum samples obtained at baseline (prior to study drug administration) and at day 30. PF4 values were normalized to total platelet count. All of the participants were on guideline-directed therapies for ACS. Additionally, LIMA samples from patients undergoing coronary bypass surgery were immunostained with PCSK9, the endothelial cell transmembrane glycoprotein CD31 (platelet endothelial cell adhesion molecule-1) and the platelet surface marker CD61 (integrin beta-3). Outcome data were summarized using medians and interquartile ranges. Results Forty-six participants were randomized in a 1:1 fashion to placebo or to evolocumab. Mean (±SD) age of the cohort was 60±13 years, 48% were women and 22% were African American. Baseline PF4 levels (expressed as ng/1k platelets) were similar between the two groups (placebo: 9.3 [4–12] vs evolocumab 8.0 [4–12], p=0.8). In the placebo group, there was a significant increase in PF4 at 30 days to 13.1 [11–14], p&amp;lt;0.01 (baseline vs 30 days). In contrast, there was no significant change from baseline in the evolocumab group at 30 days (10.7 [6–13]), which was significantly lower than the placebo group (p=0.04). Furthermore, immunostaining of LIMA specimens obtained from patients during coronary artery bypass surgery revealed colocalization of PCSK9, CD31, and CD61 on the vascular endothelial cell surface (see Figure). Conclusion PCSK9 inhibition with evolocumab decreases platelet activation in ACS patients on dual anti-platelet therapy. PCSK9 is associated with platelets and endothelial cells at the vascular endothelium. PCSK9 is a potential mediator of the interaction between platelets and vascular endothelial cells in patients with coronary artery disease. Funding Acknowledgement Type of funding sources: Other. Main funding source(s): Amgen

The LIPL study lipid panels and platelet activity in coronary heart disease

Abstract Introduction Measuring lipid panel in the fasting state can be inconvenient for patients and may aggravate their compliance. Moreover, people spend most of the day in the nonfasting state. Hence, it suggests that the changes in the process of atherosclerosis happen mainly under the influence of nonfasting lipids. Up to date, the studies in the postprandial state were primarily performed in healthy subjects. Aim This exploratory study investigates the change in lipid profile and platelet activity in patients with different cardiovascular risk profiles in the postprandial state. Methods The studied population consists of 66 patients with different cardiovascular risks: patients with coronary artery disease (CAD) and diabetes mellitus type 2 (DM2) (n=20), CAD without DM2 (n=25), and a healthy control group (n=21). Lipid variables and markers of platelet function were assessed during the fasting state and 3 and 5 hours after a standardized fat meal using a standardized oral fat tolerance test (OFTT), a milkshake with 90g of fat. The platelet activity was measured with a Multiplate test using ADP, ASPI and TRAP reagents. Results Patients with CAD and DM2 were significantly older and had the highest BMI. All patients with CAD were on acetylsalicylic acid, and 95% of CAD patients were on high-dose statins. Total cholesterol, LDL-c, Apolipoprotein A1, and Apolipoprotein B did not change during the OFTT, irrespective of the group. However, HDL-c decreased statistically significantly three and five hours after the fat loading with a peak after five hours (3.46±0.4 mg/dL, p&amp;lt;0.001). The lowest HDL-c was in the CAD and DM2 group (p=0.006). Triglycerides (TG) increased significantly during the OFTT, with a peak after 5 hours (130.2±14.5 mg/dL, p&amp;lt;0.001) irrespective of the group. There was no difference in TG concentration between the groups. Differences stayed statistically significant even after adjustment for age and BMI. Platelet activity increased after fat loading, as shown by a significantly increased thrombocyte count after three hours (p&amp;lt;0.001). Platelet activity measured by multiplate test with ADP (7.16±2.17 AU, p=0.005), ASPI (4.60±1.40 AU, p=0.005), and TRAP (11.41±3.10 AU, p=0.001) reagents increased statistically significant three hours after the fat loading. The platelet activity measured by all three reagents remained increased even after the adjustment for age and BMI (ADP: 7.14±2.10 AU, p=0.004, ASPI: 4.60±1.40 AU, p=0.006, TRAP: 11.40±3.10 AU, p=0.002). Moreover, the platelet activity measured by ADP (−13.12±4.93, p=0.030), and TRAP (−14.6±15.51, p=0.031) reagents was lower in the control group. When adjusted for age and BMI, there was no difference in the platelet activity between the three groups. Conclusion This study showed that fatty meal causes worsening of lipid profile and leads to increased platelet activity in subjects irrespective of cardiovascular risk profile. Funding Acknowledgement Type of funding sources: None.

Identification of early derangements of coagulation, hematological and biochemical profiles in patients with acute pancreatitis

BackgroundAcute pancreatitis (AP) is a severe disease involving various pathological processes. We aimed to use rapid -thromboelastography (r-TEG) combined with conventional coagulation assays (CCAs) and other laboratory tests, to identify early derangements in coagulation, hematological, and biochemical profiles in patients with AP. MethodsWe enrolled 177 patients diagnosed with AP and 121 controls. Blood samples were analyzed using r-TEG, CCAs, and hematological and biochemical tests within 2 h of patient admission. All testing parameters were compared between the patients and the controls. Pearson’s correlation coefficient was used to determine the correlation between the parameters among the patients. Logistic regression analysis was performed to evaluate the effects of the variables (demographic, coagulation, hematological and biochemical) on AP. ResultsUsing r-TEG and CCAs, we observed differences in coagulation parameters between the patients with AP and the controls. The r-TEG results showed a pro-coagulant state and increased platelet activation in AP patients. Pearson’s correlation analysis showed that inflammatory indicators were strongly correlated with coagulation/platelets in the pathological process of AP. Logistic regression analysis revealed that age, K, neutrophil (NEUT), triglyceride (TG) and blood amylase (AMY) were significantly associated with the development of AP. ConclusionCoagulation profile and platelet play essential roles in the pathogenesis of AP. Pro-coagulant state and increased platelet activation in patients with AP were demonstrated using r-TEG. The r-TEG parameter K, age, NEUT, TG, and AMY may be used as potential indicators of AP.