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Prostacyclin analogues decrease platelet aggregation but have no effect on thrombin generation, fibrin clot structure, and fibrinolysis in pulmonary arterial hypertension: PAPAYA coagulation 前列环素类似物可降低血小板聚集,但对肺动脉高压患者凝血酶生成、纤维蛋白凝块结构和纤维蛋白溶解无影响:木瓜凝血
IF 3.3 3区 医学 Q3 CELL BIOLOGY Pub Date : 2022-03-14 DOI: 10.1080/09537104.2022.2042234
Aleksander Siniarski, A. Gąsecka, Miłosz Starczyński, M. Banaszkiewicz, Szymon Darocha, A. Torbicki, M. Kurzyna, K. Filipiak, J. Nessler, G. Gajos
Abstract Prostacyclin (PGI2) analogues (epoprostenol, treprostonil, iloprost) are the cornerstone of pulmonary arterial hypertension (PAH) treatment. PGI2 analogues inhibit platelet reactivity, but their impact on coagulation and fibrinolysis parameters has not been elucidated. We compared platelet reactivity, thrombin generation, clot permeation, and lysis properties in patients with PAH treated with PGI2 analogues (n = 20) and those not receiving PGI2 analogues (n = 20). Platelet reactivity was lower in patients treated with PGI2 analogues, compared to the control group, as evaluated with arachidonic acid (ASPI), adenosine diphosphate (ADP), and thrombin receptor-activating peptide-6 (TRAP) tests (p = .009, p = .02, p = .007, respectively). In the subgroup analysis, both treprostinil and epoprostenol decreased platelet reactivity to the similar extent. There were no differences regarding thrombin generation, clot permeation, and lysis parameters in patients receiving and not receiving PGI2 analogues (p ≥ .60 for all). In the subgroup analysis, there were no differences regarding coagulation and fibrinolysis parameters between treprostinil, epoprostenol, and no PGI2 analogues. To conclude, patients with PAH treated with PGI2 analogues have reduced platelet reactivity, but similar clot formation and lysis parameters, compared to patients not receiving PGI2 analogues. Further randomized clinical trials are required to confirm these findings.
前列环素(PGI2)类似物(丙前列醇、曲前列醇、伊洛前列素)是肺动脉高压(PAH)治疗的基石。PGI2类似物抑制血小板反应性,但其对凝血和纤溶参数的影响尚未阐明。我们比较了接受PGI2类似物治疗的PAH患者(n = 20)和未接受PGI2类似物治疗的PAH患者(n = 20)的血小板反应性、凝血酶生成、血栓渗透和溶解特性。通过花生四烯酸(ASPI)、二磷酸腺苷(ADP)和凝血酶受体激活肽-6 (TRAP)试验评估,与对照组相比,接受PGI2类似物治疗的患者血小板反应性较低(p = 0.009, p = 0.02, p = 0.007)。在亚组分析中,treprostiil和epoprostenol降低血小板反应性的程度相似。在接受和未接受PGI2类似物治疗的患者中,凝血酶生成、血栓渗透和溶解参数没有差异(所有患者p≥0.60)。在亚组分析中,treprostiil、epoprostenol和无PGI2类似物在凝血和纤溶参数上没有差异。综上所述,与未接受PGI2类似物治疗的患者相比,接受PGI2类似物治疗的PAH患者血小板反应性降低,但凝块形成和溶解参数相似。需要进一步的随机临床试验来证实这些发现。
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引用次数: 2
The role of miRNAs in regulation of platelet activity and related diseases - a bioinformatic analysis miRNA在血小板活性调节和相关疾病中的作用——生物信息学分析
IF 3.3 3区 医学 Q3 CELL BIOLOGY Pub Date : 2022-03-14 DOI: 10.1080/09537104.2022.2042233
Z. Wicik, P. Czajka, C. Eyileten, A. Fitas, M. Wolska, D. Jakubik, D. von Lewinski, H. Sourij, J. Siller-Matula, M. Postuła
Abstract MicroRNAs (miRNAs) are small, non-coding RNAs, able to regulate cellular functions by induction of mRNA degradation and post-transcriptional repression of gene expression. Platelets are the major source of circulating miRNAs, with significant regulatory potential on cardiovascular pathophysiology and other diseases. MiRNAs have been shown to modify the expression of platelet proteins, which influence the platelets reactivity. Circulating miRNAs can be determined from plasma, serum, or whole blood, and they can be used as diagnostic and prognostic biomarkers as well as therapeutic targets including cardiovascular diseases (CVDs). Herein, we present original results from bioinformatic analyses, which identified top 22 platelet-related miRNAs including hsa-miR-320a, hsa-miR-16-5p, hsa-miR-106a-5p, hsa-miR-320b, hsa-miR-15a-5p, hsa-miR-15b-5p, hsa-miR-195-5p, hsa-miR-92a-3p as widely involved in platelet reactivity and associated diseases, including CVDs, Alzheimer’s and cerebrovascular diseases, cancer and hypertension. Analysis focused on the identification of the highly regulatory targets shared between those miRNAs identified 43 of them. Best ranked genes associated with overall platelet activity and most susceptible for noncoding regulation were PTEN, PIK3R1, CREB1, APP, and MAPK1. Top targets also strongly associated with CVDs were VEGFA, IGF1, ESR1, BDNF, and PPARG. Top targets associated with other platelet-related diseases including cancer identified in our study were TP53, KRAS, and CCND1. The most affected pathways by top miRNAs and top targets included diseases of signal transduction by Growth Factor Receptors (GDFRs) and second messengers, platelet activation, signaling, and aggregation, signaling by VEGF, MAPK family signaling cascades, and signaling by Interleukins. Terms specific only for platelet-related miRNAs included coronary artery disease, platelet degranulation, and neutrophil degranulation, while for the top platelet-related genes it was Estrogen Signaling Receptor (ESR) mediated signaling, extra-nuclear estrogen signaling, and endometriosis. Our results show the novel features of platelet physiology and may provide a basis for further clinical studies focused on platelet reactivity. They also show in which aspects miRNAs can be promising biomarkers of platelet-related pathological processes.
摘要微小RNA(miRNA)是一种小型的非编码RNA,能够通过诱导mRNA降解和转录后抑制基因表达来调节细胞功能。血小板是循环miRNA的主要来源,对心血管病理生理学和其他疾病具有重要的调节潜力。miRNA已被证明可以改变血小板蛋白的表达,从而影响血小板的反应性。循环miRNA可以从血浆、血清或全血中测定,它们可以用作诊断和预后的生物标志物以及治疗靶点,包括心血管疾病(CVD)。在此,我们提供了生物信息学分析的原始结果,这些结果确定了前22种血小板相关的miRNA,包括hsa-miR-320a、hsa-miR-16-5p、hsa-iR-106a-5p、hsa-miR-320b、hsa-miR-15a-5p,hsa-miR-15b-5p、hsa-miR-195-5p、hsa-1miR-92a-3p,它们广泛参与血小板反应性和相关疾病,包括心血管疾病、阿尔茨海默病和脑血管疾病、癌症和高血压。分析的重点是识别这些miRNA之间共享的高度调节靶点,确定了其中43个。PTEN、PIK3R1、CREB1、APP和MAPK1是与总体血小板活性相关且对非编码调控最敏感的基因。与心血管疾病密切相关的主要靶点是VEGFA、IGF1、ESR1、BDNF和PPARG。与包括癌症在内的其他血小板相关疾病相关的主要靶点是TP53、KRAS和CCND1。受顶级miRNA和顶级靶点影响最大的途径包括生长因子受体(GDFR)和第二信使的信号转导疾病、血小板活化、信号传导和聚集、VEGF的信号传导、MAPK家族信号级联和白细胞介素的信号传导。仅针对血小板相关miRNA的术语包括冠状动脉疾病、血小板脱颗粒和中性粒细胞脱颗粒,而针对血小板相关的顶级基因,则是雌激素信号受体(ESR)介导的信号传导、核外雌激素信号传导和子宫内膜异位症。我们的研究结果显示了血小板生理学的新特征,并可能为进一步关注血小板反应性的临床研究提供基础。他们还展示了miRNA在哪些方面可以成为血小板相关病理过程的有前途的生物标志物。
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引用次数: 10
Circulating microRNAs as biomarkers and mediators of platelet activation 循环microrna作为血小板活化的生物标志物和介质
IF 3.3 3区 医学 Q3 CELL BIOLOGY Pub Date : 2022-03-09 DOI: 10.1080/09537104.2022.2042236
C. Gutmann, M. Mayr
Abstract Platelets are essential mediators of physiological hemostasis and pathological thrombosis. Currently available tests and markers of platelet activation did not prove successful in guiding treatment decisions for patients with cardiovascular disease, justifying further research into novel markers of platelet reactivity. Platelets contain a variety of microRNAs (miRNAs) and are a major contributor to the extracellular circulating miRNA pool. Levels of platelet-derived miRNAs in the circulation have been associated with different measures of platelet activation as well as antiplatelet therapy and have therefore been implied as potential new markers of platelet reactivity. In contrast to the ex vivo assessment of platelet reactivity by current platelet function tests, miRNA measurements may enable assessment of platelet reactivity in vivo. It remains to be seen however, whether miRNAs may aid clinical diagnostics. Major limitations in the platelet miRNA research field remain the susceptibility to preanalytical variation, non-standardized sample preparation and data normalization that hampers inter-study comparisons. In this review, we provide an overview of the literature on circulating miRNAs as biomarkers of platelet activation, highlighting the underlying biology, the application in patients with cardiovascular disease and antiplatelet therapy and elaborating on technical limitations regarding their quantification in the circulation.
血小板是生理性止血和病理性血栓形成的重要介质。目前可用的血小板活化测试和标志物在指导心血管疾病患者的治疗决策方面并不成功,这证明进一步研究血小板反应性的新标志物是合理的。血小板含有多种microrna (miRNA),是细胞外循环miRNA库的主要贡献者。循环中血小板来源的mirna水平与血小板活化的不同措施以及抗血小板治疗有关,因此被认为是血小板反应性的潜在新标志物。与目前通过血小板功能测试对血小板反应性的体外评估不同,miRNA测量可以在体内评估血小板反应性。然而,mirna是否有助于临床诊断还有待观察。血小板miRNA研究领域的主要局限性仍然是易受分析前变异、非标准化样品制备和数据归一化的影响,这妨碍了研究间的比较。在这篇综述中,我们提供了关于循环mirna作为血小板活化的生物标志物的文献综述,重点介绍了潜在的生物学,在心血管疾病患者和抗血小板治疗中的应用,并详细说明了在循环中量化mirna的技术局限性。
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引用次数: 5
Efficacy of platelet transfusion in cardiac surgery 血小板输注在心脏手术中的疗效
IF 3.3 3区 医学 Q3 CELL BIOLOGY Pub Date : 2022-03-08 DOI: 10.1080/09537104.2022.2026905
Lisa Blath, J. Martens, N. Rahe‐Meyer
Abstract Massive diffuse bleeding is still a problem in cardiovascular surgery. The first line treatment is platelet concentrate transfusion, although there is still insufficient information regarding efficacy, quantity, and timing. The objective of this prospective cohort study was to find out whether the amount of 4 apheresis platelet concentrates could reduce intraoperative bleeding and improve viscoelasticity and aggregometry. 10 patients were enrolled intraoperatively because of life-threatening diffuse bleeding after cardiopulmonary bypass and received 4 apheresis platelet concentrates back-to-back. The units were given every 5 minutes. After every unit, thromboelastometry, performed by ROTEM®, and aggregometry, performed by Multiplate®, were done together with Hematocrit, Hemoglobin, and Platelet Count. Hematocrit and Hemoglobin showed a statistically significant decrease of 14%, whereas Platelet Count showed a statistically significant increase of 205%. MCE-EXTEM increased statistically significant: 46%. There was no statistically significant increase in both ADP and COL results. Even a series of 4 platelet concentrates did not comprehensively improve both essential components of an adequate hemostasis: viscoelasticity and aggregation. Just the transfusion of platelet concentrates alone did not build a sufficient strategy improving hemostasis and reducing bleeding. A positive effect of surgical packing on stopping the bleeding could be seen.
大量弥漫性出血仍是心血管外科手术的难题。一线治疗是输注浓缩血小板,尽管关于其疗效、数量和时间的信息仍然不足。本前瞻性队列研究的目的是探讨4单采血小板浓缩物的用量是否可以减少术中出血,改善粘弹性和聚集性。10例患者因体外循环术后弥漫性出血危及生命,术中入组,连续4次采血小板浓缩。单位每5分钟给出一次。每个单元结束后,用ROTEM®进行血栓弹性测定,用Multiplate®进行聚集测定,并与血细胞比容、血红蛋白和血小板计数一起进行。红细胞压积和血红蛋白下降了14%,血小板计数上升了205%。MCE-EXTEM增加了46%,具有统计学意义。ADP和COL结果均无统计学意义的升高。即使是一系列的4种血小板浓缩物也不能全面改善充分止血的两个基本组成部分:粘弹性和聚集。单纯输注血小板浓缩物并不能充分改善止血和减少出血。手术填塞对止血有积极作用。
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引用次数: 4
Anti-PF4/polyanion antibodies in COVID-19 patients are associated with disease severity and pulmonary pathology COVID-19患者的抗pf4 /多阴离子抗体与疾病严重程度和肺部病理相关
IF 3.3 3区 医学 Q3 CELL BIOLOGY Pub Date : 2022-02-28 DOI: 10.1080/09537104.2022.2042238
T. Ueland, I. Hausberg, T. V. Mørtberg, T. Dahl, T. V. Lerum, A. Michelsen, T. Ranheim, Katerina Nezvalova Henriksen, A. Dyrhol-Riise, P. Holme, T. Aaløkken, O. Skjønsberg, A. Barratt-Due, M. Ahlén, P. Aukrust, B. Halvorsen
Abstract Thromboembolic events are frequent and associated with poor outcome in severe COVID-19 disease. Anti-PF4/polyanion antibodies are related to heparin-induced thrombocytopenia (HIT) and thrombus formation, but data on these antibodies in unselected COVID-19 populations are scarce. We assessed the presence of anti-PF4/polyanion antibodies in prospectively collected serum from an unselected cohort of hospitalized COVID-19 patients and evaluated if elevated levels could give prognostic information on ICU admission and respiratory failure (RF), were associated with markers of inflammation, endothelial activation, platelet activation, coagulation and fibrosis and were associated with long-term pulmonary CT changes. Five out of 65 patients had anti-PF4/polyanion reactivity with OD ≥0.200. These patients had more severe disease as reflected by ICU admission without any evidence of HIT. They also had signs of enhanced inflammation and fibrinogenesis as reflected by elevated ferritin and osteopontin, respectively, during the first 10 days of hospitalization. Increased ferritin and osteopontin persisted in these patients at 3 months follow-up, concomitant with pulmonary CT pathology. Our finding shows that the presence of anti-PF4/polyanion antibodies in unselected hospitalized COVID−19 patients was not related to HIT, but was associated with disease severity, inflammation, and pulmonary pathology after 3 months.
在重症COVID-19疾病中,血栓栓塞事件频繁发生并与不良预后相关。抗pf4 /聚阴离子抗体与肝素诱导的血小板减少症(HIT)和血栓形成有关,但在未选择的COVID-19人群中关于这些抗体的数据很少。我们评估了从未选择的住院COVID-19患者中前瞻性收集的血清中抗pf4 /聚阴离子抗体的存在,并评估水平升高是否可以提供ICU入院和呼吸衰竭(RF)的预后信息,是否与炎症、内皮活化、血小板活化、凝血和纤维化标志物相关,以及是否与长期肺部CT变化相关。65例患者中有5例具有抗pf4 /聚阴离子反应性,OD≥0.200。这些患者入院时病情更严重,没有HIT的证据。在住院的前10天,他们也有炎症和纤维蛋白生成增强的迹象,这分别反映在铁蛋白和骨桥蛋白的升高上。在随访3个月时,这些患者的铁蛋白和骨桥蛋白持续升高,并伴有肺部CT病理。我们的研究结果表明,在未选择的住院COVID - 19患者中,抗pf4 /聚阴离子抗体的存在与HIT无关,但与疾病严重程度、炎症和3个月后的肺部病理有关。
{"title":"Anti-PF4/polyanion antibodies in COVID-19 patients are associated with disease severity and pulmonary pathology","authors":"T. Ueland, I. Hausberg, T. V. Mørtberg, T. Dahl, T. V. Lerum, A. Michelsen, T. Ranheim, Katerina Nezvalova Henriksen, A. Dyrhol-Riise, P. Holme, T. Aaløkken, O. Skjønsberg, A. Barratt-Due, M. Ahlén, P. Aukrust, B. Halvorsen","doi":"10.1080/09537104.2022.2042238","DOIUrl":"https://doi.org/10.1080/09537104.2022.2042238","url":null,"abstract":"Abstract Thromboembolic events are frequent and associated with poor outcome in severe COVID-19 disease. Anti-PF4/polyanion antibodies are related to heparin-induced thrombocytopenia (HIT) and thrombus formation, but data on these antibodies in unselected COVID-19 populations are scarce. We assessed the presence of anti-PF4/polyanion antibodies in prospectively collected serum from an unselected cohort of hospitalized COVID-19 patients and evaluated if elevated levels could give prognostic information on ICU admission and respiratory failure (RF), were associated with markers of inflammation, endothelial activation, platelet activation, coagulation and fibrosis and were associated with long-term pulmonary CT changes. Five out of 65 patients had anti-PF4/polyanion reactivity with OD ≥0.200. These patients had more severe disease as reflected by ICU admission without any evidence of HIT. They also had signs of enhanced inflammation and fibrinogenesis as reflected by elevated ferritin and osteopontin, respectively, during the first 10 days of hospitalization. Increased ferritin and osteopontin persisted in these patients at 3 months follow-up, concomitant with pulmonary CT pathology. Our finding shows that the presence of anti-PF4/polyanion antibodies in unselected hospitalized COVID−19 patients was not related to HIT, but was associated with disease severity, inflammation, and pulmonary pathology after 3 months.","PeriodicalId":20268,"journal":{"name":"Platelets","volume":"33 1","pages":"640 - 644"},"PeriodicalIF":3.3,"publicationDate":"2022-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41986683","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}
引用次数: 4
Stability and utility of flow cytometric platelet activation tests: A modality to bridge the gap between diagnostic demand and supply 流式细胞仪血小板活化测试的稳定性和实用性:一种弥合诊断需求和供应之间差距的方法
IF 3.3 3区 医学 Q3 CELL BIOLOGY Pub Date : 2022-02-28 DOI: 10.1080/09537104.2022.2042232
R. Dave, T. Geevar, G. Chellaiya, J. Mammen, Ramya Vijayan, Ashok Samuel, M. Gowri, S. Nair
Abstract Light transmission aggregometry (LTA) is the gold standard for the diagnosis of platelet function disorders (PFDs). The requirement of customized aggregometer, large blood volume, normal platelet count and processing within 4 hours of venipuncture for LTA makes platelet function testing inaccessible to wider population. Flow cytometric platelet activation test (PACT) may overcome these limitations. This study compares the performance of PACT with LTA, characterizes diagnostic patterns of PFDs on PACT and assesses the stability of PACT beyond 4 hours of venipuncture in controls (n = 5) at different temperature conditions. LTA and PACT were performed in 121 healthy controls and 66 patients with suspected PFD. PACT had excellent agreement (kappa = 0.93) with LTA and 94.1% sensitivity, 98.5% specificity. PACT had distinct patterns in Bernard Soulier Syndrome (n = 10), Glanzmann Thrombasthenia (n = 24), δ-granule disorder (n = 7), and other PFDs (n = 12). PACT could assess platelet function in patients (14%) with thrombocytopenia/lipemia wherein LTA was inconclusive. PACT was stable up to 24 hours in samples stored/transported at 2–8◦C. The results of utility and stability are only valid for the specific markers, agonist concentrations, and conditions investigated in this paper. PACT is a useful modality for the diagnosis of PFD, especially in children, thrombocytopenia cases or in the setup where an aggregometer is not readily available.
摘要光透射聚集度测定法(LTA)是诊断血小板功能紊乱(PFD)的金标准。LTA需要定制聚集度计、大血容量、正常血小板计数和静脉穿刺后4小时内处理,这使得更广泛的人群无法进行血小板功能测试。流式细胞仪血小板活化试验(PACT)可以克服这些限制。本研究比较了PACT和LTA的性能,表征了PFDs在PACT上的诊断模式,并评估了对照组(n=5)在不同温度条件下静脉穿刺4小时后PACT的稳定性。对121名健康对照和66名疑似PFD患者进行了LTA和PACT。PACT与LTA具有极好的一致性(kappa=0.93),敏感性为94.1%,特异性为98.5%。PACT在Bernard-Soulier综合征(n=10)、Glanzmann血栓衰弱(n=24)、δ颗粒障碍(n=7)和其他PFD(n=12)中具有不同的模式。PACT可以评估血小板减少症/脂血症患者(14%)的血小板功能,其中LTA不确定。在2–8储存/运输的样品中,PACT稳定长达24小时◦C.效用和稳定性的结果仅对本文研究的特定标记物、激动剂浓度和条件有效。PACT是诊断PFD的一种有用模式,尤其是在儿童、血小板减少症病例或聚集度计不可用的情况下。
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引用次数: 1
Human Platelets and Influenza Virus: Internalization and Platelet Activation. 人血小板与流感病毒:内化和血小板活化。
IF 3.3 3区 医学 Q3 CELL BIOLOGY Pub Date : 2022-02-17 DOI: 10.1080/09537104.2021.1961710
Josiah Bote, Heather A Corkrey, Milka Koupenova

Influenza infection has long been associated with prothrombotic outcomes in patients and platelets are the blood component predominantly responsible for thrombosis. In this review, we outline what is known about influenza interaction with human platelets, virion internalization, and viral RNA sensing, and the consequent impact on platelet function. We further discuss activation of platelets by IgG-influenza complexes and touch upon mechanisms of environmental platelet activation that relate to prothrombotic outcomes in patients during infection.

长期以来,流感感染与患者的血栓形成预后有关,而血小板是导致血栓形成的主要血液成分。在这篇综述中,我们概述了流感与人类血小板的相互作用、病毒粒子内化和病毒RNA感知,以及随之而来的对血小板功能的影响。我们进一步讨论了igg -流感复合物对血小板的激活,并触及了感染期间与患者血栓形成前结果相关的环境血小板激活机制。
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引用次数: 5
Platelet-HIV: interactions and their implications. 血小板- hiv:相互作用及其影响。
IF 3.3 3区 医学 Q3 CELL BIOLOGY Pub Date : 2022-02-17 DOI: 10.1080/09537104.2021.2019695
Sidney W Whiteheart

While it is clear that platelets interact with viruses, the ramifications and mechanisms of those interactions are still being defined for each type of viral infection. HIV/AIDS+ represents a potentially unique example of how viremia affects platelets since the increasing efficacy of antiretroviral therapeutics (ART) has made it a chronic disease that increases the risk of cardiovascular disease. In this opinion article, we discuss some of the open questions about how platelets interact with HIV. What happens to a virion once it binds a platelet? What is the nature of virus-induced platelet activation? Are platelets a normal part of the immune response to viremia that has been co-opted to increase the spread of HIV? The answers to these and similar questions will help define how platelet-directed therapeutics might be used in treating HIV/AIDS+ patients.

虽然血小板与病毒的相互作用是明确的,但对于每种类型的病毒感染,这些相互作用的后果和机制仍然是明确的。艾滋病毒/艾滋病+可能是病毒血症如何影响血小板的一个独特例子,因为抗逆转录病毒疗法(ART)的疗效日益提高,使其成为一种慢性病,增加了心血管疾病的风险。在这篇观点文章中,我们讨论了一些关于血小板如何与HIV相互作用的开放性问题。病毒粒子与血小板结合后会发生什么?病毒诱导血小板活化的本质是什么?血小板是病毒血症免疫反应的正常组成部分吗?病毒血症已被用来增加HIV的传播。这些问题和类似问题的答案将有助于确定血小板导向疗法如何用于治疗HIV/AIDS+患者。
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引用次数: 0
Editorial: special review series on viruses and platelets. 社论:关于病毒和血小板的特别评论系列。
IF 3.3 3区 医学 Q3 CELL BIOLOGY Pub Date : 2022-02-17 DOI: 10.1080/09537104.2021.2020491
Matthew T Rondina
Platelets are increasingly recognized for their broad repertoire of activities spanning hemostatic, inflammatory, and immune continuums. In many cases, platelet functions cooperate to bridge these continuums, effectively triggering responses that may act collectively and catalytically to mediate thrombotic, inflammatory, and immune activities [1–3]. These cooperative responses have led to the creation of the term “immunothrombosis,” which emphasizes the closely woven interplay between inflammation, immunity, and thrombosis. As the second most common circulating blood cell, platelets are centrally positioned in the vasculature to trigger immunothrombosis. Platelets possess a repertoire of intracellular and stored molecules (often in granule compartments that can be secreted) and surface anchored receptors. The array of proteins, lipids, and RNAs possessed by platelets allow these small anucleate cells to sense and respond to diverse signals, including those generated during infectious settings. For example, platelets possess the RNA and/or protein for nearly all toll-like receptors (TLRs) [4,5]. TLRs are one of the several surface ligands allowing viruses to bind to platelets. In addition to TLRs, platelets also express other binding proteins, including β3 integrin, DC-SIGN, and FcRyIIA, which enable virions to bind to, engage with, and/or enter platelets. In addition to these receptor-mediated interactions, platelets may also actively take up virions through a variety of other mechanisms, including clathrin-mediated endocytosis (CME) and pinocytosis [6]. Often, more than one factor is required for internalization of viruses by platelets. Systemic agonists and pathogen particles generated as viruses enter their host and replicate may also be sensed or recognized by platelets, leading to downstream activation responses and signaldependent binding to, and communication with, leukocytes. These molecules include danger-associated molecular patterns (DAMPs; including HMGB1, S100 proteins, interleukin 1 [IL-1] family members, type interferons [IFN], and tumor necrosis factor alpha [TNF-α]) and pathogen associated molecular patterns (PAMPs; including nucleic acid motifs, ssRNA, dsRNA, and unmethylated CpG motifs). Platelets, once activated, are primed to interact and aggregate with leukocytes (e.g., heterotypic aggregation). Increased platelet–leukocyte interactions can be observed in patients infected with influenza, SARS-CoV-2, and dengue infection – among others [7–12]. These interactions can promote inflammatory cytokine synthesis (such as MCP-1, IL-1β, IL-8, and IL-10), neutrophil extracellular trap (NET) formation, and antigen-dependent T cell responses [3,13,14]. Platelets also secrete numerous molecules, such as platelet factor 4 (PF4), RANTES, and P-selectin, which may directly or indirectly mediate the pathogenesis of viral infections. The net effect of these interactions is generally thought to promote immunothrombosis, although the full range
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引用次数: 0
The efficacy and safety of thrombopoietin receptor agonists in patients with chronic liver disease undergoing elective procedures: a systematic review and meta-analysis. 接受择期手术的慢性肝病患者使用血小板生成素受体激动剂的有效性和安全性:系统回顾和荟萃分析。
IF 3.3 3区 医学 Q3 CELL BIOLOGY Pub Date : 2022-01-02 Epub Date: 2021-01-18 DOI: 10.1080/09537104.2020.1859102
Ingrid Lindquist, Sven R Olson, Ang Li, Hanny Al-Samkari, Janice H Jou, Owen J T McCarty, Joseph J Shatzel

Thrombopoietin receptor agonists (TPO-RAs) can mitigate preprocedural thrombocytopenia in patients with chronic liver disease (CLD) however their effects on procedural outcomes is unclear. In this meta-analysis, we aimed to better define the efficacy, thrombotic risk and bleeding mitigation associated with the use of preoperative TPO-RAs in patients with CLD. We performed a systematic review and meta-analysis of randomized placebo-controlled clinical trials to assess the use of preprocedural TPO-RAs in patients with CLD, searching MEDLINE, EMBASE and the Cochrane library database. Six publications comprising eight randomized trials (1229 patients; 717 received TPO-RAs, 512 received placebo) and three unique TPO-RAs were retrieved. The majority of the included procedures were endoscopic. TPO-RAs were significantly more likely to result in a preoperative platelet count greater than 50 x 109/L (72.1% vs 15.6%, RR 4.8, 95% CI 3.6-6.4 p < .00001. NNT 1.8) and reduced the incidence of platelet transfusions (22.5% vs 67.8%, RR 0.33, 95% CI 0.3-0.4 p < .00001. NNT 2.2). Total periprocedural bleeding was decreased in patients who received TPO-RAs (11.6% vs 15.6%, RR 0.64, 95% CI 0.5-0.9 p = .01. NNT 24.7) and there was no increase in the rate of thrombosis (2.2% vs 1.8% RR 1.25, 95% CI 0.6-2.9 p = .60. NNH 211.1). In patients with CLD the use of preprocedural TPO-RAs resulted in significant increased platelet counts, and decreased the incidence of platelet transfusions as compared to placebo. TPO use likewise decreased the incidence of total periprocedural bleeding without increasing the rate of thrombosis.

促血小板生成素受体激动剂(TPO-RAs)可减轻慢性肝病(CLD)患者术前血小板减少症,但其对手术结果的影响尚不明确。在这项荟萃分析中,我们旨在更好地界定在 CLD 患者术前使用 TPO-RAs 的相关疗效、血栓风险和出血缓解情况。我们检索了 MEDLINE、EMBASE 和 Cochrane 图书馆数据库,对随机安慰剂对照临床试验进行了系统回顾和荟萃分析,以评估在 CLD 患者中使用术前 TPO-RAs 的情况。共检索到六篇出版物,包括八项随机试验(1229 例患者;717 例接受 TPO-RAs 治疗,512 例接受安慰剂治疗)和三项独特的 TPO-RAs。纳入的大多数手术都是内窥镜手术。TPO-RAs 使术前血小板计数大于 50 x 109/L 的可能性明显增加(72.1% vs 15.6%,RR 4.8,95% CI 3.6-6.4 p p = .01。NNT 24.7),血栓形成率没有增加(2.2% vs 1.8% RR 1.25,95% CI 0.6-2.9 p = .60。)与安慰剂相比,CLD 患者术前使用 TPO-RAs 可显著增加血小板计数,降低血小板输注的发生率。TPO的使用同样降低了围手术期出血的发生率,但没有增加血栓形成的发生率。
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