Platelets最新文献

{"title":"Platelet glycogenolysis is important for energy production and function.","authors":"Kanakanagavalli Shravani Prakhya, Hemendra Vekaria, Daniёlle M Coenen, Linda Omali, Joshua Lykins, Smita Joshi, Hammodah R Alfar, Qing Jun Wang, Patrick Sullivan, Sidney W Whiteheart","doi":"10.1080/09537104.2023.2222184","DOIUrl":"10.1080/09537104.2023.2222184","url":null,"abstract":"<p><p>Although the presence of glycogen in platelets was established in the 1960s, its importance to specific functions (<i>i.e</i>., activation, secretion, aggregation, and clot contraction) remains unclear. Patients with glycogen storage disease often present with increased bleeding and glycogen phosphorylase (GP) inhibitors, when used as treatments for diabetes, induce bleeding in preclinical studies suggesting some role for this form of glucose in hemostasis. In the present work, we examined how glycogen mobilization affects platelet function using GP inhibitors (CP316819 and CP91149) and a battery of <i>ex vivo</i> assays. Blocking GP activity increased glycogen levels in resting and thrombin-activated platelets and inhibited platelet secretion and clot contraction, with minimal effects on aggregation. Seahorse energy flux analysis and metabolite supplementation experiments suggested that glycogen is an important metabolic fuel whose role is affected by platelet activation and the availability of external glucose and other metabolic fuels. Our data shed light on the bleeding diathesis in glycogen storage disease patients and offer insights into the potential effects of hyperglycemia on platelets.</p>","PeriodicalId":20268,"journal":{"name":"Platelets","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10658951/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9609392","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The complementary roles of VAMP-2, -3, and -7 in platelet secretion and function.","authors":"Smita Joshi, Kanakanagavalli Shravani Prakhya, Alexis N Smith, Harry Chanzu, Ming Zhang, Sidney W Whiteheart","doi":"10.1080/09537104.2023.2237114","DOIUrl":"10.1080/09537104.2023.2237114","url":null,"abstract":"<p><p>Platelet secretion requires Soluble N-ethylmaleimide Sensitive Attachment Protein Receptors (SNAREs). Vesicle SNAREs/Vesicle-Associated Membrane Proteins (v-SNAREs/VAMPs) on granules and t-SNAREs in plasma membranes mediate granule release. Platelet VAMP heterogeneity has complicated the assessment of how/if each is used and affects hemostasis. To address the importance of VAMP-7 (V7), we analyzed mice with global deletions of V3 and V7 together or platelet-specific deletions of V2, V3, and global deletion of V7. We measured the kinetics of cargo release, and its effects on three injury models to define the context-specific roles of these VAMPs. Loss of V7 minimally affected dense and α granule release but did affect lysosomal release. V3^-/-7^-/- and V2^Δ3^Δ7^-/- platelets showed partial defects in α and lysosomal release; dense granule secretion was unaffected. <i>In vivo</i> assays showed that loss of V2, V3, and V7 caused no bleeding or occlusive thrombosis. These data indicate a role for V7 in lysosome release that is partially compensated by V3. V7 and V3, together, contribute to α granule release, however none of these deletions affected hemostasis/thrombosis. Our results confirm the dominance of V8. When it is present, deletion of V2, V3, or V7 alone or in combination minimally affects platelet secretion and hemostasis.</p>","PeriodicalId":20268,"journal":{"name":"Platelets","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10564522/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41210085","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"α-Synuclein is the major platelet isoform but is dispensable for activation, secretion, and thrombosis.","authors":"Alexis N Smith, Smita Joshi, Harry Chanzu, Hammodah R Alfar, Kanakanagavalli Shravani Prakhya, Sidney W Whiteheart","doi":"10.1080/09537104.2023.2267147","DOIUrl":"10.1080/09537104.2023.2267147","url":null,"abstract":"<p><p>Platelets play many roles in the vasculature ensuring proper hemostasis and maintaining integrity. These roles are facilitated, in part, by cargo molecules released from platelet granules via <u>S</u>oluble <u>N</u>SF <u>A</u>ttachment <u>P</u>rotein <u>R</u>eceptor (SNARE) mediated membrane fusion, which is controlled by several protein-protein interactions. Chaperones have been characterized for t-SNAREs (<i>i.e</i>. Munc18b for Syntaxin-11), but none have been clearly identified for v-SNAREs. α-Synuclein has been proposed as a v-SNARE chaperone which may affect SNARE-complex assembly, fusion pore opening, and thus secretion. Despite its abundance and that it is the only isoform present, α-synuclein's role in platelet secretion is uncharacterized. In this study, immunofluorescence showed that α-synuclein was present on punctate structures that co-stained with markers for α-granules and lysosomes and in a cytoplasmic pool. We analyzed the phenotype of α-synuclein^-/- mice and their platelets. Platelets from knockout mice had a mild, agonist-dependent secretion defect but aggregation and spreading <i>in vitro</i> were unaffected. Consistently, thrombosis/hemostasis were unaffected in the tail-bleeding, FeCl₃ carotid injury and jugular vein puncture models. None of the platelet secretory machinery examined, <i>e.g</i>. the v-SNAREs, were affected by α-synuclein's loss. The results indicate that, despite its abundance, α-synuclein has only a limited role in platelet function and thrombosis.</p>","PeriodicalId":20268,"journal":{"name":"Platelets","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10629845/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71485176","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Performance evaluation of PLT-H (hybrid-channel platelet) under various interferences and application studies for platelet transfusion decisions.","authors":"Qi Cai, Han Lin, Ping Guo","doi":"10.1080/09537104.2023.2287064","DOIUrl":"https://doi.org/10.1080/09537104.2023.2287064","url":null,"abstract":"<p><p>The hybrid-channel platelet counting method (PLT-H) is a new platelet counting technique proposed by Mindray of China. In this study, we aimed to evaluate the accuracy of this technique in various situations and its reliability in platelet transfusion decision-making. A total of 378 venous blood samples were tested. Using the immunological PLT counting method recommended by the International Council for Standardization in Hematology as the reference method (PLT-IRM), Passing-Bablok regression and Bland-Altman analysis were performed on the PLT-H results. The anti-interference performance of PLT-H under different interference levels was explored using intergroup comparisons, and confusion matrices were analyzed at various transfusion cutoff values. In the absence of interference, there was a strong correlation between PLT-H and PLT-IRM (<i>r</i> = 0.993, 95% CI: 0.990-0.996). Under various interference conditions, the correlation between PLT-H and PLT-IRM was between 0.963 and 0.992, with an average deviation of -14.56 to -2.02. The performance of PLT-H against interference did not change significantly with increasing levels of small RBCs, large PLTs, and RBC fragments (<i>P</i> = .5704, 0.0832, 0.9893). In low-value samples (PLT <100 × 10⁹/L), the coefficient of variation (CV) for PLT-H was less than 7.6%, regardless of the presence or absence of interfering substances. In addition, there was a high agreement between PLT-H and PLT-IRM (ICC = 0.972). Confusion matrice analysis at each medical decision level showed similarity to methods using the fluorescence channel (PLT-O) and superiority to the impedance channel (PLT-I). Compared with PLT-I, PLT-H has higher accuracy in PLT counting, stronger anti-interference ability, better performance in low-value samples at no extra economic cost and can be more useful for platelet transfusion decision-making. PLT-H is a novel method for platelet counting that offers higher accuracy, providing physicians with the ability to make better medical decisions, particularly in cases where values are low, or interference is present. As it does not require additional reagents, it is highly likely to replace PLT-I and become the mainstream method for platelet counting in the future.</p>","PeriodicalId":20268,"journal":{"name":"Platelets","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138462152","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tailoring antiplatelet therapy in older patients with coronary artery disease.","authors":"Mila Kovacevic, Graziella Pompei, Vijay Kunadian","doi":"10.1080/09537104.2023.2285446","DOIUrl":"10.1080/09537104.2023.2285446","url":null,"abstract":"<p><p>The older population represents a unique subset of patients due to a higher rate of comorbidities and risk factors, which can lead to a higher rate of ischemic and bleeding events. As a result, older adults are mainly underrepresented or excluded from randomized trials. Although the advancement in the percutaneous coronary intervention field with the development of new technologies, techniques, and potent antiplatelet therapy led to a reduction of ischemic risk, there is still a concern regarding bleeding hazards. Apart from the global utilization of less invasive trans-radial approach and proton pump inhibitors to reduce bleeding risk, proper tailoring of antiplatelet therapy in the older person is imperative. So far, several antiplatelet drugs have been introduced in different clinical scenarios, with dual antiplatelet therapy (combination of acetylsalicylic acid and P2Y₁₂ inhibitor) recommended after percutaneous coronary intervention. The decision on the choice of antiplatelet drug and the DAPT duration is challenging and should be based on the relationship between ischemia and bleeding with the purpose of reducing ischemic events but not at the expense of increased bleeding complications. This is particularly important in the older population, where the evidence is obscure. The main objective of this review is to summarize the available evidence on contemporary antiplatelet therapy and different approaches of de-escalation strategies in older patients after percutaneous coronary intervention.</p>","PeriodicalId":20268,"journal":{"name":"Platelets","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138482808","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of exercise on platelet reactivity after myocardial infarction: a randomized clinical trial.","authors":"Talia Falcão Dalçóquio, Mayara Alves Dos Santos, Leandro Silva Alves, Flávia Bittar Brito Arantes, Larissa Ferreira-Santos, Maria Urbana Pinto Brandão Rondon, Remo Holanda M Furtado, Aline Gehlen Ferrari, Paulo Roberto Genestreti Rizzo, Rocio Salsoso, Andre Franci, Luciano Moreira Baracioli, Maria Janieire de Nazare Nunes Alves, Carlos Eduardo Negrão, José Carlos Nicolau","doi":"10.1080/09537104.2022.2139821","DOIUrl":"10.1080/09537104.2022.2139821","url":null,"abstract":"<p><p>Exercise training (ET) can lower platelet reactivity in patients with cardiovascular risk factors. However, the effects of ET on platelet reactivity in higher-risk patients is unknown. The aim of this study was to evaluate the effects of ET on platelet reactivity in patients with recent myocardial infarction (MI). Ninety patients were randomly assigned 1 month post-MI to the intervention (patients submitted to a supervised ET program) or control group. All patients were on dual antiplatelet therapy (DAPT). Platelet reactivity by VerifyNow-P2Y₁₂ (measured by P2Y₁₂ reaction units - PRUs) test was determined at baseline and at the end of 14 ± 2 weeks of follow-up at rest (primary endpoint), and multiplate electrode aggregometry (MEA) adenosine diphosphate (ADP) and aspirin (ASPI) tests were performed immediately before and after the maximal cardiopulmonary exercise test (CPET) at the same time points (secondary endpoints). Sixty-five patients (mean age 58.9 ± 10 years; 73.8% men; 60% ST elevation MI) completed follow-up (control group, n = 31; intervention group, n = 34). At the end of the follow-up, the mean platelet reactivity was 172.8 ± 68.9 PRUs and 166.9 ± 65.1 PRUs for the control and intervention groups, respectively (p = .72). Platelet reactivity was significantly increased after the CPET compared to rest at the beginning and at the end of the 14-week follow-up (among the intervention groups) by the MEA-ADP and MEA-ASPI tests (p < .01 for all analyses). In post-MI patients on DAPT, 14 weeks of supervised ET did not reduce platelet reactivity. Moreover, platelet reactivity was increased after high-intensity exercise (ClinicalTrials.gov: NCT02958657; https://clinicaltrials.gov/ct2/show/NCT02958657).</p>","PeriodicalId":20268,"journal":{"name":"Platelets","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40474991","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"European Delphi panel to build consensus on tapering and discontinuing thrombopoietin receptor agonists in immune thrombocytopenia.","authors":"Adele Barlassina, Tomás José González-López, Nichola Cooper, Francesco Zaja","doi":"10.1080/09537104.2023.2170999","DOIUrl":"10.1080/09537104.2023.2170999","url":null,"abstract":"<p><p>To establish pan-European consensus on tapering and discontinuing thrombopoietin receptor agonists (TPO-RAs) in patients with immune thrombocytopenia (ITP), we applied a three-step Delphi technique consisting of a one-to-one interview round and two online survey rounds. Three healthcare professionals (HCPs) from Italy, Spain, and the United Kingdom formed the Steering Committee (SC), which advised on study design, panelist selection, and survey development. A literature review also informed the development of the consensus statements. Likert scales were used to collect quantitative data on panelists' level of agreement. Twelve hematologists representing nine European countries assessed 121 statements spanning three categories: (1) patient selection; (2) tapering and discontinuation strategies; (3) post-discontinuation management. Consensus was reached on approximately half of the statements in each category (32.2%; 44.6%; 66%). Panelists agreed on patients' main selection criteria, patients' involvement in decision-making, tapering strategies, and follow-up criteria. Areas not reaching consensus were risk factors and predictors of successful discontinuation, monitoring intervals, and rates of successful discontinuation or relapse. This lack of consensus signals knowledge and practice gaps among European countries and suggests the need for the development of clinical practice guidelines that outline a pan-European, evidence-based approach to tapering and discontinuing TPO-RAs.</p>","PeriodicalId":20268,"journal":{"name":"Platelets","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9348671","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"How can we use proteomics to learn more about platelets?","authors":"Joseph E Aslan","doi":"10.1080/09537104.2023.2217932","DOIUrl":"10.1080/09537104.2023.2217932","url":null,"abstract":"<p><p>Proteomics tools provide a powerful means to identify, detect, and quantify protein-related details in studies of platelet phenotype and function. Here, we consider how historical and recent advances in proteomics approaches have informed our understanding of platelet biology, and, how proteomics tools can be used going forward to advance studies of platelets. It is now apparent that the platelet proteome is comprised of thousands of different proteins, where specific changes in platelet protein systems can accompany alterations in platelet function in health and disease. Going forward, many challenges remain in how to best carry out, validate and interpret platelet proteomics experiments. Future studies of platelet protein post-translational modifications such as glycosylation, or studies that take advantage of single cell proteomics and top-down proteomics methods all represent areas of interest to profiling and more richly understanding platelets in human wellness and disease.</p>","PeriodicalId":20268,"journal":{"name":"Platelets","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11524195/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9907532","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genetic background of thrombocytosis in mice mimicking hereditary thrombocytosis in humans.","authors":"Hiroyuki Kimura, Masahiro Onozawa, Takanori Teshima","doi":"10.1080/09537104.2023.2276697","DOIUrl":"10.1080/09537104.2023.2276697","url":null,"abstract":"","PeriodicalId":20268,"journal":{"name":"Platelets","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71522413","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Platelet-derived mitochondria transfer facilitates wound-closure by modulating ROS levels in dermal fibroblasts.","authors":"Soomin Kim,&nbsp;Yujin Kim,&nbsp;Shin-Hye Yu,&nbsp;Seo-Eun Lee,&nbsp;Jong Hyeok Park,&nbsp;Gayoung Cho,&nbsp;Chul Choi,&nbsp;Kyuboem Han,&nbsp;Chun-Hyung Kim,&nbsp;Young Cheol Kang","doi":"10.1080/09537104.2022.2151996","DOIUrl":"https://doi.org/10.1080/09537104.2022.2151996","url":null,"abstract":"<p><p>Platelets are known to improve the wound-repair capacity of mesenchymal stem cells (MSCs) by transferring mitochondria intercellularly. This study aimed to investigate whether direct transfer of mitochondria (pl-MT) isolated from platelets could enhance wound healing <i>in vitro</i> using a cell-based model. Wound repairs were assessed by 2D gap closure experiment in wound scratch assay using human dermal fibroblasts (hDFs). Results demonstrated that pl-MT were successfully internalized into hDFs. It increased cell proliferation and promoted the closure of wound gap. Importantly, pl-MT suppressed both intracellular and mitochondrial ROS production induced by hydrogen peroxide, cisplatin, and TGF-β in hDFs. Taken together, these results suggest that pl-MT transfer might be used as a potential therapeutic strategy for wound repair.</p>","PeriodicalId":20268,"journal":{"name":"Platelets","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9564190","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}