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Cerebrovascular Diseases (Basel,... 2015Platelet-leukocyte aggregation (PLA) and platelet activation are found to be on the higher side in ischemic stroke patients. The correlation of PLA with clinical...
BACKGROUND
Platelet-leukocyte aggregation (PLA) and platelet activation are found to be on the higher side in ischemic stroke patients. The correlation of PLA with clinical features has not been intensively investigated and the influence of genetic factors on PLA is still unexplored. The interaction of platelets with leukocytes is mainly determined by the proteins encoded by six genes: P-Selectin (SELP encodes CD62P) on the thrombocyte binding to P-Selectin-Glycoprotein-Ligand-1 (PSGL1) on the leukocyte, intracellular-adhesion-molecule 2 (ICAM2) interacting with Integrin alpha M (ITGAM) and Glycoprotein 1b-alpha (GP1BA) binding to Integrin alpha L (ITGAL).
METHODS
Seventy-nine patients with acute ischemic stroke and 151 controls without vascular disease from a single German center were enrolled. A neurologist and a neuroradiologist ascertained clinical and radiological features. PLA and platelet activation were analyzed using flow cytometry with various antibodies. Coding as well as tagging SNPs in six genes determining PLA were genotyped. Three groups of parameters were correlated with each other: (i) clinical and radiological parameters, (ii) laboratory parameters, (iii) genetic parameters. For the comparisons, robust nonparametric statistical tests were applicable.
RESULTS
PLA and platelet activation were higher in ischemic stroke patients compared to controls. Both, anticoagulant and antiplatelet treatment in the patient group affected platelet activation but not PLA. PLA correlated weakly with measures of stroke severity but not with thrombus length or stroke etiology. The association of SNP rs2228315 in the P-Selectin Glycoprotein Ligand-1-gene (PSGL1) with ischemic stroke and platelet activation was significant before correction for multiple testing while a trend was observed for the association with PLA. Regression analysis revealed that (i) platelet activation was an independent determinant of stroke, (ii) that PLA correlated with stroke, sex, age and platelet activation and (iii) that platelet activation correlated only with stroke. None of the SNPs survived in the regression analysis for stroke, PLA or platelet activation as dependent variables.
CONCLUSIONS
The most important result of our study is that PLA and platelet activation are independent of other vascular risk factors correlated with stroke in our sample. In addition, we identified the missense SNP rs2228315 in the PSGL1-gene as a candidate polymorphism for ischemic stroke-related PLA. Association between this SNP and stroke as well as coronary artery disease has also been shown by two other studies.
Topics: Adult; Aged; Aged, 80 and over; Blood Platelets; Brain Ischemia; Female; Humans; Leukocytes; Male; Middle Aged; P-Selectin; Platelet Activation; Platelet Aggregation; Platelet Function Tests; Risk Factors; Stroke
PubMed: 25720421
DOI: 10.1159/000375396 -
Current Protocols Jun 2021Platelets are small but very abundant blood cells that play a key role in hemostasis, contributing to thrombus formation at sites of injury. The ability of platelets to...
Platelets are small but very abundant blood cells that play a key role in hemostasis, contributing to thrombus formation at sites of injury. The ability of platelets to perform this function, as well as functions in immunity and inflammation, is dependent on the presence of cell surface glycoproteins and changes in their quantity and conformation after platelet stimulation. In this article, we describe the characterization of platelet surface markers and platelet function using platelet-specific fluorescent probes and flow cytometry. Unlike traditional platelet tests, immunophenotypic analysis of platelets by flow cytometry allows the analysis of platelet function in samples with very low platelet counts as often encountered in clinical situations. © 2021 Wiley Periodicals LLC. Basic Protocol 1: Immunophenotyping of platelet surface receptors Alternate Protocol: Fix-first method for immunophenotyping of platelet surface receptors Basic Protocol 2: Determination of platelet activation using P-selectin expression and/or PAC1 binding Basic Protocol 3: Determination of procoagulant platelets using annexin V binding or antibodies specific for coagulation factor V/Va or X/Xa Support Protocol: Preparation of isolated platelets.
Topics: Blood Platelets; Factor Va; Flow Cytometry; Immunophenotyping; Platelet Activation
PubMed: 34170638
DOI: 10.1002/cpz1.178 -
Seminars in Thrombosis and Hemostasis Apr 2016Flow cytometry enables studies of several different aspects of platelet function in response to a variety of platelet agonists. This can be done using only a small... (Review)
Review
Flow cytometry enables studies of several different aspects of platelet function in response to a variety of platelet agonists. This can be done using only a small volume of whole blood, and also in blood with low platelet counts. These properties, together with the increasing number of flow cytometers available in hospitals worldwide, make flow cytometry an interesting option for laboratories interested in studies of platelet function in different clinical settings. This review focuses on practical issues regarding the use of flow cytometry for platelet function testing. It provides an overview of available activation markers, platelet agonists, and experimental setup issues. The review summarizes previous experience and factors important to consider to perform high-quality platelet function testing by flow cytometry. It also discusses its current use and possibilities and challenges for future use of flow cytometry in clinical settings.
Topics: Blood Platelet Disorders; Blood Platelets; Flow Cytometry; Humans; Platelet Activation; Platelet Aggregation; Platelet Function Tests; Reproducibility of Results; Sensitivity and Specificity; Thrombosis
PubMed: 26886398
DOI: 10.1055/s-0035-1570082 -
Aging May 2018The cardiovascular effects of testosterone and dihydrotestosterone are generally attributed to their modulatory action on lipid and glucose metabolism. However, no...
The cardiovascular effects of testosterone and dihydrotestosterone are generally attributed to their modulatory action on lipid and glucose metabolism. However, no studies suggest that circulating androgen levels influence the activation and reactivity of blood platelets - one of the main components of the haemostasis system directly involved in atherosclerosis. The levels of testosterone, dihydrotestosterone and oestradiol in plasma from men and women aged from 60 to 65 years were measured by LC-MS; the aim was to identify any potential relationships between sex steroid levels and the markers of platelet activation (surface membrane expression of GPII/IIIa complex and P-selectin) and platelet reactivity in response to arachidonate, collagen or ADP, monitored with whole blood aggregometry and flow cytometry. The results of the part of the study indicate that the concentrations of testosterone and its reduced form, dihydrotestosterone are significantly negatively associated with platelet activation and reactivity. These observations were confirmed in an model: testosterone and dihydrotestosterone significantly inhibited platelet aggregation triggered by arachidonate or collagen. Our findings indicate that testosterone and dihydrotestosterone are significant haemostatic steroids with inhibitory action on blood platelets in older people.
Topics: Aged; Blood Platelets; Dihydrotestosterone; Estradiol; Female; Humans; Male; Middle Aged; Platelet Activation; Platelet Aggregation; Testosterone
PubMed: 29723157
DOI: 10.18632/aging.101438 -
Physiological Research Mar 2022Exposure to high altitudes and exercise alters body's physiology and may cause acute cardiovascular events. Platelet activation is one of the key players in these...
Exposure to high altitudes and exercise alters body's physiology and may cause acute cardiovascular events. Platelet activation is one of the key players in these events. Therefore, we investigated the effect of vigorous exercise at higher altitude (2650 m) on platelet aggregation and serum markers of platelet activation. 14 healthy subjects performed a step incremental ergometer test until exhaustion at the Environmental Research Station (UFS, 2650 m) at Zugspitze. Platelet aggregation and serum levels of endothelin-1, soluble p-selectin, platelet factor 4 and Chromogranin A were measured. Platelet activation was significantly enhanced after exercise at high altitude compared to measures immediately prior exercise. We detected significantly enhanced serum levels of endothelin-1 and soluble p-selectin whereas chromogranin A and platelet factor 4 remained unchanged. This effect might be due to increased endothelin-1 levels causing pulmonary vasoconstriction, rheological changes and direct platelet activation. This might be of clinical relevance, especially in patients with pre-existing diseases.
Topics: Altitude; Exercise; Humans; P-Selectin; Platelet Activation; Platelet Aggregation
PubMed: 35043652
DOI: 10.33549/physiolres.934768 -
High Blood Pressure & Cardiovascular... Sep 2015Many drugs are nowadays available to inhibit platelet activation and aggregation, especially in patients with acute coronary syndromes and undergoing percutaneous... (Review)
Review
Many drugs are nowadays available to inhibit platelet activation and aggregation, especially in patients with acute coronary syndromes and undergoing percutaneous coronary intervention with stent implantation. Primary targets are represented by enzymes or receptors involved in platelet activation. Genetic mutations in these targets contribute to the inter-individual variability in platelet responses therefore weakening the efficacy of antiplatelet agents. High on treatment platelet reactivity is a condition characterized by low levels of platelet inhibition despite the use of antiplatelet drugs. This could be responsible for re-infarction, stent-thrombosis and strokes, affecting short and long-term prognosis after coronary revascularization. So far, to test antiplatelet resistance either the assessment of platelet function or the identification of genetic carriers of poly morphisms have been pursued. Although several methods are now available to test platelet reactivity, it is still debated whether its routine assessment gives real benefits in clinical practice. The present review aims at examining current evidences on genetic polymorphisms affecting optimal platelet inhibition.
Topics: Blood Platelets; Clopidogrel; Cytochrome P-450 CYP2C19; Drug Resistance; Humans; Membrane Glycoproteins; Mutation; Platelet Activation; Platelet Adhesiveness; Platelet Aggregation; Platelet Aggregation Inhibitors; Polymorphism, Genetic; Receptors, Adrenergic, alpha; Receptors, Adrenergic, beta; Ticlopidine
PubMed: 25986078
DOI: 10.1007/s40292-015-0104-5 -
International Journal of Cardiology Nov 2023
Topics: Humans; Platelet Activation; Syndrome; Takotsubo Cardiomyopathy
PubMed: 37586422
DOI: 10.1016/j.ijcard.2023.131256 -
Methods in Molecular Biology (Clifton,... 2017Many pathogenic bacteria have been reported to interact with human platelets to mediate platelet activation and aggregation. The importance of these interactions to the...
Many pathogenic bacteria have been reported to interact with human platelets to mediate platelet activation and aggregation. The importance of these interactions to the immune response or pathogenesis of bacterial infection has not been clarified. It may therefore be valuable to assess platelet responses mediated by diverse strains of bacteria. Here, I describe a method to study platelet integrin activation and granule release using flow cytometry, and a complementary method to study platelet aggregation using a dedicated platelet aggregometer. The combination of these methods represents a rapid and cost-effective strategy to provide mechanistic insight on the type of platelet response mediated by the bacteria.
Topics: Bacterial Infections; Biomarkers; Blood Coagulation; Blood Platelets; Flow Cytometry; Humans; Kinetics; Platelet Activation; Platelet Aggregation; Platelet-Rich Plasma
PubMed: 27914085
DOI: 10.1007/978-1-4939-6673-8_17 -
Cirugia Y Cirujanos 2020Platelets, in addition to participating in atherosclerosis, play a very active role in the immune response of this disease since they have the ability to interact with... (Review)
Review
Platelets, in addition to participating in atherosclerosis, play a very active role in the immune response of this disease since they have the ability to interact with various inflammatory cells, in addition to secreting cytokines, chemokines, growth factors, etc. The functions of platelets go beyond their interaction with the endothelium, as they participate in creating an inflammatory environment, which contributes to the loss of homeostasis. On the other hand, platelet-derived microparticles induce the activation of other platelets, of endothelial cells and in recruiting leukocytes. For all the above, platelets and the inflammatory environment can be considered as possible therapeutic targets to prevent the development of atherosclerosis and the events associated with it.
Topics: Atherosclerosis; Cell-Derived Microparticles; Endothelium, Vascular; Humans; Inflammation; Platelet Activation
PubMed: 32116325
DOI: 10.24875/CIRU.19000725 -
Current Drug Targets 2015Platelets play a crucial role in immune responses. Impaired platelet activation may cause persistent mucosal inflammation through P-selectin, CD40-CD40L and other... (Review)
Review
Platelets play a crucial role in immune responses. Impaired platelet activation may cause persistent mucosal inflammation through P-selectin, CD40-CD40L and other systems influencing granulocytes, macrophages or endothelial cells. Pharmacological regulation of platelet activation may reduce thromboembolism and limit the interaction of platelets with endothelial and inflammatory cells, in turn weakening the inflammatory responses. In this review we focus on pathophysiological activities of platelets in inflammatory bowel diseases and discuss the studies on currently available anti-platelet therapies in the treatment of gastrointestinal inflammation. Finally, we provide a prospective view to new anti-platelet agents currently under development.
Topics: Animals; Blood Platelets; Humans; Inflammatory Bowel Diseases; Platelet Activation; Platelet Aggregation Inhibitors
PubMed: 25585124
DOI: 10.2174/1389450116666150113122229