Platelets最新文献

{"title":"Recent advances on GPIb-IX-V complex.","authors":"Renhao Li","doi":"10.1080/09537104.2022.2075146","DOIUrl":"https://doi.org/10.1080/09537104.2022.2075146","url":null,"abstract":"An abundant receptor complex exclusively expressed on the surface of platelets and megakaryocytes, glycoprotein (GP)Ib-IX-V complex plays a major role in hemostasis and thrombosis. Its importance is corroborated by the bleeding symptoms in patients with congenital defects in this complex [1]. GPIbα, the main subunit in this receptor complex, contains the binding domain for plasma protein von Willebrand factor (VWF) and thrombin [2–4]. Recent studies, utilizing genetically altered animal models as well as new cutting-edge biomechanical, molecular, and cellular techniques, produced exciting insights on the inner workings of this receptor complex and expanded its involvement into platelet clearance, cancer metastasis, and inflammatory complications. Some studies have also identified potential new ligands of GPIbα, such as the SARS-CoV-2 spike protein [5], although the underlying mechanisms await verification and further elucidation [6]. Thus, it is appropriate time to review recent advances on GPIb-IX -V and related pathways. Dr Jerry Ware led the development of the first genetically altered murine model for GPIbα, which validates the applicability of mice to study GPIb-IX-V and to model related diseases [7]. In his review, Dr Ware describes various knockout and transgenic murine models that alter either receptor expression or an aspect of GPIb-IX functions. Their characterization has firmly established critical involvement of GPIb-IX in platelet generation, activation, and clearance and also generated valuable insights on the underlying mechanisms. Critical features associated with each murine model, along with important caveats, are noted and compared, which would be important in data interpretation as these animal models are increasingly applied to assess the involvement of GPIb-IX in a variety of physiological or pathophysiological processes. Dr Edward Quach is a young investigator who reported key evidence for the defining mechanical feature of GPIb-IX activation [8]. His review focuses on recent exciting advances in understanding how GPIb-IX activation critically drives platelet clearance in several common thrombocytopenic conditions. A common feature in the form of a conformational change in GPIb-IX appears in these disease settings, which may be potentially applicable to other more complications involving thrombocytopenia. Dr Xiaoping Du first demonstrated the association of GPIX with GPIbα and GPIbβ to form a highly integrated GPIb-IX complex [9]. Here, he and his coworkers review the intracellular signaling events that are induced by GPIb-IX ligands and lead up to the activation of integrin αIIbβ3 in platelets. Intracellular molecules associated with cytoplasmic domains of GPIb-IX, such as 14-3-3ζ and filamin, are required for these signaling pathways. Additional downstream kinases and related molecules, connecting extensively with other signaling pathways, are also delineated. Finally, although GPV is associated with GPIb-IX and highly ex","PeriodicalId":20268,"journal":{"name":"Platelets","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2022-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9378636/pdf/nihms-1812396.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10023382","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":"Successful treatment of acquired amegakaryocytic thrombocytopenia with eltrombopag and immunosuppressant.","authors":"Hong Tian,&nbsp;Danqing Kong,&nbsp;Yun Li,&nbsp;Chengyuan Gu,&nbsp;Ziqiang Yu,&nbsp;Zhaoyue Wang,&nbsp;Depei Wu,&nbsp;Jie Yin","doi":"10.1080/09537104.2021.2012140","DOIUrl":"https://doi.org/10.1080/09537104.2021.2012140","url":null,"abstract":"<p><p>Acquired amegakaryocytic thrombocypenia (AAMT) is an extremely rare hematologic disorder and standard treatment strategy has not been established. We described herein two cases of AAMT who were fully responded to eltrombopag and immunosuppressant. Patient 1 was refractory to steroid, IVIG and recombinant human thrombopoietin (rhTPO). Patient 2 did not respond to high dosage of steroid, IVIG, rhTPO and rituximab. Moreover, his AAMT progressed to aplastic anemia in 5 months. Both patients took eltrombopag and immunosuppressant, then they achieved long-term remission without obvious side effects. Our findings suggest that this combination can be a valuable alternative in AAMT.</p>","PeriodicalId":20268,"journal":{"name":"Platelets","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2022-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39820280","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":"Glycoprotein V : the unsolved GPV puzzle.","authors":"Quentin Kimmerlin,&nbsp;Sylvie Moog,&nbsp;Catherine Ravanat,&nbsp;Catherine Strassel,&nbsp;François Lanza","doi":"10.1080/09537104.2021.2022114","DOIUrl":"https://doi.org/10.1080/09537104.2021.2022114","url":null,"abstract":"<p><p>Glycoprotein V (GPV) is a highly expressed 82 KDa platelet surface transmembrane protein which is loosely attached to the GPIb-IX complex. Despite remaining questions concerning its function, GPV presents several unique features which have repercussions in hematology, atherothrombosis, immunology and transfusion. GPV is specifically expressed in platelets and megakaryocytes and is an ideal marker and reporter gene for the late stages of megakaryopoiesis. The ectodomain of GPV can be released by a number of proteases, namely thrombin, elastase and ADAM10 and 17. Although it was originally proposed as a thrombin receptor, this hypothesis was abandoned since thrombin activation was preserved after blockade of GPV cleavage and in <i>Gp5</i> knockout mice. The combined potential of GPV to reflect the direct action of thrombin, platelet exposure to strong agonists and inflammatory conditions has led one to evaluate its utility as a marker in the context of atherothrombosis. Increased plasma levels of soluble GPV have notably been recorded in myocardial infarction, stroke and venous thromboembolism. It is also highly valued in transfusion to monitor platelet storage lesions. GPV presents several polymorphisms, which are a possible source of alloantibodies, while autoantibodies have been frequently detected in immune thrombocytopenia. The real biological function of this glycoprotein nevertheless remains an enigma, despite the respectively decreased and increased responses to low concentrations of collagen and thrombin observed in <i>Gp5</i> knockout mice. Current studies are exploring its role in modulating general or VWF-induced platelet signaling, which could bear relevance in thrombosis and platelet clearance.</p>","PeriodicalId":20268,"journal":{"name":"Platelets","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2022-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39654120","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":"Developmental differences of <i>in vitro</i> cultured murine bone marrow- and fetal liver-derived megakaryocytes.","authors":"Ivana Bertović,&nbsp;Ana Bura,&nbsp;Antonija Jurak Begonja","doi":"10.1080/09537104.2021.2007869","DOIUrl":"https://doi.org/10.1080/09537104.2021.2007869","url":null,"abstract":"<p><p>Multiple lines of evidence support differences in the megakaryopoiesis during development. Murine <i>in vitro</i> models to study megakaryopoiesis employ cultured megakaryocytes MKs derived from adult bone marrow (BM) or fetal livers (FL) of mouse embryos. Mouse models allow to study the molecular basis for cellular changes utilizing conditional or knock-out models and permit further <i>in vitro</i> genetic or pharmacological manipulations. Despite being extensively used, MKs cultured from these two sources have not been systematically compared. In the present study, we compared BM- and FL-derived MKs, assessing their size, proplatelet production capacity, expression of common MK markers (αIIb, β3, GPIb α, β) and cytoskeletal proteins (filamin A, β1-tubulin, actin), the subcellular appearance of α-granules (VWF), membranes (GPIbβ) and cytoskeleton (F-actin) throughout <i>in vitro</i> development. We demonstrate that FL MKs although smaller in size, spontaneously produce more proplatelets than BM MKs and at earlier stages express more β1-tubulin. In addition, early FL MKs show increased internal GPIbβ staining and present higher GPIbβ (early and late) and VWF (late stages) total fluorescence intensity (TFI)/cell size than BM MKs. BM MKs have up-regulated TPO signaling corresponding to their bigger size and ploidy, without changes in c-Mpl. Expressing endogenous β1-tubulin or the presence of heparin improves BM MKs ability to produce proplatelets. These data suggest that FL MKs undergo cytoplasmic maturation earlier than BM MKs and that this, in addition to higher β1-tubulin levels and GPIb, supported with an extensive F-actin network, could contribute to more efficient proplatelet formation <i>in vitro</i>.</p>","PeriodicalId":20268,"journal":{"name":"Platelets","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2022-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39820285","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":"Signaling mechanisms of the platelet glycoprotein Ib-IX complex.","authors":"Yaping Zhang,&nbsp;Samuel M Ehrlich,&nbsp;Cheng Zhu,&nbsp;Xiaoping Du","doi":"10.1080/09537104.2022.2071852","DOIUrl":"https://doi.org/10.1080/09537104.2022.2071852","url":null,"abstract":"<p><p>The glycoprotein Ib-IX (GPIb-IX) complex mediates initial platelet adhesion to von Willebrand factor (VWF) immobilized on subendothelial matrix and endothelial surfaces, and transmits VWF binding-induced signals to stimulate platelet activation. GPIb-IX also functions as part of a mechanosensor to convert mechanical force received via VWF binding into intracellular signals, thereby greatly enhancing platelet activation. Thrombin binding to GPIb-IX initiates GPIb-IX signaling cooperatively with protease-activated receptors to synergistically stimulate the platelet response to low-dose thrombin. GPIb-IX signaling may also occur following the binding of other GPIb-IX ligands such as leukocyte integrin α_Mβ₂ and red cell-derived semaphorin 7A, contributing to thrombo-inflammation. GPIb-IX signaling requires the interaction between the cytoplasmic domains of GPIb-IX and 14-3-3 protein and is mediated through Src family kinases, the Rho family of small GTPases, phosphoinositide 3-kinase-Akt-cGMP-mitogen-activated protein kinase, and LIM kinase 1 signaling pathways, leading to calcium mobilization, integrin activation, and granule secretion. This review summarizes the current understanding of GPIb-IX signaling.</p>","PeriodicalId":20268,"journal":{"name":"Platelets","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2022-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9378482/pdf/nihms-1806984.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10080371","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":"Platelet response to aspirin in UK and Irish pregnancy cohorts: a genome-wide approach.","authors":"Fionnuala Mone,&nbsp;Juhi K Gupta,&nbsp;Marie M Phelan,&nbsp;Shireen Meher,&nbsp;Lu Yung Lian,&nbsp;Ben Francis,&nbsp;Eunice Zhang,&nbsp;Cecilia Mulcahy,&nbsp;Ana Alfirevic,&nbsp;Fionnuala M Mcauliffe,&nbsp;Kate Navaratnam","doi":"10.1080/09537104.2021.2007872","DOIUrl":"https://doi.org/10.1080/09537104.2021.2007872","url":null,"abstract":"<p><p>A multi-center prospective cross-sectional and genome-wide association study (GWAS) recruited pregnant women taking low dose aspirin. Objectives were to (i) develop pregnancy-specific 95% reference intervals for a range of laboratory based platelet function tests (PFTs); (ii) select an optimal and acceptable PFT that reflected aspirin's COX-1 inhibition in women with confirmed aspirin adherence in pregnancy; and (iii) identify genomic variants that may influence pregnant women's platelet response to aspirin.The study included two independent cohorts of pregnant women. A range of PFTs and matched phenotyping with urinary 11-dehydrothromboxane B₂ (11DTXB2) and nuclear magnetic resonance (NMR) spectroscopy detection of urinary salicyluric acid as a measure of aspirin adherence were performed. Genome-wide data was acquired from the UK Biobank Axiom® (Thermo Fisher Scientific). 11DTXB2 in combination with adherence testing with NMR salicyluric acid was an accurate and acceptable testing strategy for detecting biochemical aspirin responsiveness in pregnant women, with the provision of relevant reference ranges. GWAS meta-analysis found no significant single nucleotide polymorphisms in association with response to aspirin in pregnancy. Further evaluation in relation to effective dosing of aspirin in pregnancy and optimizing the benefits to specific subgroups should now be a priority for future research.</p>","PeriodicalId":20268,"journal":{"name":"Platelets","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2022-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39722992","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":"Higher body mass index raises immature platelet count: potential contribution to obesity-related thrombosis.","authors":"Lucy J Goudswaard, Laura J Corbin, Kate L Burley, Andrew Mumford, Parsa Akbari, Nicole Soranzo, Adam S Butterworth, Nicholas A Watkins, Dimitri J Pournaras, Jessica Harris, Nicholas J Timpson, Ingeborg Hers","doi":"10.1080/09537104.2021.2003317","DOIUrl":"10.1080/09537104.2021.2003317","url":null,"abstract":"<p><p>Higher body mass index (BMI) is a risk factor for thrombosis. Platelets are essential for hemostasis but contribute to thrombosis when activated pathologically. We hypothesized that higher BMI leads to changes in platelet characteristics, thereby increasing thrombotic risk. The effect of BMI on platelet traits (measured by Sysmex) was explored in 33 388 UK blood donors (INTERVAL study). Linear regression showed that higher BMI was positively associated with greater plateletcrit (PCT), platelet count (PLT), immature platelet count (IPC), and side fluorescence (SFL, a measure of mRNA content used to derive IPC). Mendelian randomization (MR), applied to estimate a causal effect with BMI proxied by a genetic risk score, provided causal estimates for a positive effect of BMI on both SFL and IPC, but there was little evidence for a causal effect of BMI on PCT or PLT. Follow-up analyses explored the functional relevance of platelet characteristics in a pre-operative cardiac cohort (COPTIC). Linear regression provided observational evidence for a positive association between IPC and agonist-induced whole blood platelet aggregation. Results indicate that higher BMI raises the number of immature platelets, which is associated with greater whole blood platelet aggregation in a cardiac cohort. Higher IPC could therefore contribute to obesity-related thrombosis.</p>","PeriodicalId":20268,"journal":{"name":"Platelets","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2022-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9114156","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":"Potential and limitations of PKA/ PKG inhibitors for platelet studies.","authors":"Valentina Shpakova,&nbsp;Natalia Rukoyatkina,&nbsp;Ulrich Walter,&nbsp;Stepan Gambaryan","doi":"10.1080/09537104.2021.2003316","DOIUrl":"https://doi.org/10.1080/09537104.2021.2003316","url":null,"abstract":"<p><p>Cyclic nucleotides (cAMP and cGMP) and corresponding protein kinases, protein kinase A (PKA) and protein kinase G (PKG), are the main intracellular mediators of endothelium-derived platelet inhibitors. Pharmacological PKA/PKG inhibitors are often used to discriminate between these two kinase activities and to analyze their underlying mechanisms. Previously we showed that all widely used PKG inhibitors (KT5823, DT3, RP isomers) either did not inhibit PKG or inhibited and even activated platelets independently from PKG. In this study, we examined several PKA inhibitors as well as inhibitors of adenylate and guanylate cyclases to reveal their effects on platelets and establish whether they are mediated by PKA/PKG. The commonly used PKA inhibitor H89 inhibited both PKA and PKG but PKA-independently inhibited thrombin-induced platelet activation. In our experiments, KT5720 did not inhibit PKA and had no effect on platelet activation. PKI inhibited PKA activity in platelets but also strongly PKA-independently activated platelets. Inhibition of adenylate and guanylate cyclases may be an alternative approach to analyze PKA/PKG function. Based on our previous and presented data, we conclude that all results where the mentioned PKA inhibitors were used for the analysis of PKA activity in intact platelets should be considered with caution.</p>","PeriodicalId":20268,"journal":{"name":"Platelets","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2022-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39790204","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":"Early recognition of sepsis-induced coagulopathy using the C2PAC index: a ratio of soluble type C lectin-like receptor 2 (sCLEC-2) level and platelet count.","authors":"Hiroyasu Ishikura,&nbsp;Yuhei Irie,&nbsp;Masahide Kawamura,&nbsp;Kota Hoshino,&nbsp;Yoshihiko Nakamura,&nbsp;Mariko Mizunuma,&nbsp;Junichi Maruyama,&nbsp;Maiko Nakashio,&nbsp;Katsue Suzuki-Inoue,&nbsp;Taisuke Kitamura","doi":"10.1080/09537104.2021.2019694","DOIUrl":"https://doi.org/10.1080/09537104.2021.2019694","url":null,"abstract":"<p><p>C-type lectin-like receptor 2 (CLEC-2) is a platelet-activated receptor expressed on the surface of platelet membranes. Soluble CLEC-2 (sCLEC-2) has been receiving attention as a predictive marker for thrombotic predisposition. The present study examined the relationship between sCLEC-2 level and degree of coagulation disorder in septic patients. Seventy septic patients were divided into the sepsis-induced disseminated intravascular coagulation (DIC) (SID) group (n = 44) and non-SID group (n = 26). The sCLEC-2 levels were compared between the two groups. Because we suspected that the sCLEC-2 level was affected by the platelet count, we calculated the sCLEC-2/platelet count ratio (C2PAC index). We further divided septic patients into four groups using the Japanese Association for Acute Medicine (JAAM) DIC scoring system (DIC scores: 0-1, 2-3, 4-5, and 6-8). The C2PAC index was significantly higher in the SID group (2.6 ± 1.7) compared with the non-SID group (1.2 ± 0.5) (<i>P</i> < .001). The C2PAC indexes in the four JAAM DIC score groups were 0.9 ± 0.3, 1.1 ± 0.3, 1.7 ± 0.7, and 3.6 ± 1.0, respectively, and this index increased significantly as the DIC score increased (<i>P</i> < .001). According to the receiver-operating curve analysis, the area under the curve (AUC) and optimal cutoff value for the diagnosis of SID were 0.8051 and 1.4 (sensitivity, 75.0%; specificity, 76.9%), respectively. When the C2PAC index and D-dimer level, one of the main fibrinolytic markers, were selected as predictive markers for SID diagnosis in stepwise multiple logistic regression analysis, it was possible to diagnose SID with a high probability (AUC, 0.9528; sensitivity, 0.9545; specificity, 0.8846). The C2PAC index is a useful predictor of SID progression and diagnosis in septic patients.</p>","PeriodicalId":20268,"journal":{"name":"Platelets","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2022-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39856561","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":"Platelets and open access - a new era dawns.","authors":"Elizabeth E Gardiner,&nbsp;Gayle M Halford,&nbsp;Paul Harrison,&nbsp;William A E Parker,&nbsp;Steve P Watson","doi":"10.1080/09537104.2022.2083340","DOIUrl":"https://doi.org/10.1080/09537104.2022.2083340","url":null,"abstract":"","PeriodicalId":20268,"journal":{"name":"Platelets","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2022-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10841392","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}