PlateletsPub Date : 2024-12-01Epub Date: 2024-05-14DOI: 10.1080/09537104.2024.2336104
Tomás José González-López, Abelardo Bárez, Ángel Bernardo-Gutiérrez, Silvia Bernat, Fernando Fernández-Fuertes, José María Guinea de Castro, Reyes Jiménez-Bárcenas, Isidro Jarque
{"title":"Real-life clinical practice in Spain in the setting of new drug availability for ITP treatment. A Delphi-based Spanish expert panel consensus.","authors":"Tomás José González-López, Abelardo Bárez, Ángel Bernardo-Gutiérrez, Silvia Bernat, Fernando Fernández-Fuertes, José María Guinea de Castro, Reyes Jiménez-Bárcenas, Isidro Jarque","doi":"10.1080/09537104.2024.2336104","DOIUrl":"https://doi.org/10.1080/09537104.2024.2336104","url":null,"abstract":"<p><p>Immune thrombocytopenia (ITP) is a common autoimmune hematological disorder. Despite this, diagnosis is still challenging due to clinical heterogeneity and the lack of a specific diagnostic test. New findings in the pathology and the availability of new drugs have led to the development of different guidelines worldwide. In the present study, the Delphi methodology has been used to get a consensus on the management of adult patients with ITP in Spain and to help in decision-making. The Delphi questionnaire has been designed by a scientific ad hoc committee and has been divided into 13 topics, with a total of 127 items, covering the maximum possible scenarios for the management of ITP. As a result of the study, a total consensus of 81% has been reached. It is concluded that this Delphi consensus provides practical recommendations on topics related to diagnosis and management of ITP patients to help doctors to improve outcomes. Some aspects remain unclear, without consensus among the experts. Thus, more advances are needed to optimize ITP management.</p>","PeriodicalId":20268,"journal":{"name":"Platelets","volume":"35 1","pages":"2336104"},"PeriodicalIF":3.3,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140922732","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":"Hemin regulates platelet clearance in hemolytic disease by binding to GPIbα.","authors":"Man Zhao, Dongxin Peng, Yuxuan Li, Minwei He, Yulong Zhang, Qianqian Zhou, Sujing Sun, Ping Ma, Liping Lv, Xiaohui Wang, Linsheng Zhan","doi":"10.1080/09537104.2024.2383642","DOIUrl":"10.1080/09537104.2024.2383642","url":null,"abstract":"<p><p>Hemolysis is associated with thrombosis and vascular dysfunction, which are the pathological components of many diseases. Hemolytic products, including hemoglobin and hemin, activate platelets (PLT). Despite its activation, the effect of hemolysis on platelet clearance remains unclear, It is critical to maintain a normal platelet count and ensure that circulating platelets are functionally viable. In this study, we used hemin, a degradation product of hemoglobin, as a potent agonist to treat platelets and simulate changes in vivo in mice. Hemin treatment induced activation and morphological changes in platelets, including an increase in intracellular Ca<sup>2+</sup> levels, phosphatidylserine (PS) exposure, and cytoskeletal rearrangement. Fewer hemin-treated platelets were cleared by macrophages in the liver after transfusion than untreated platelets. Hemin bound to glycoprotein Ibα (GPIbα), the surface receptor in hemin-induced platelet activation and aggregation. Furthermore, hemin decreased GPIbα desialylation, as evidenced by reduced Ricinus communis agglutinin I (RCA- I) binding, which likely extended the lifetime of such platelets in vivo. These data provided new insight into the mechanisms of GPIbα-mediated platelet activation and clearance in hemolytic disease.</p>","PeriodicalId":20268,"journal":{"name":"Platelets","volume":"35 1","pages":"2383642"},"PeriodicalIF":2.5,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141788893","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}
PlateletsPub Date : 2024-12-01DOI: 10.1080/09537104.2024.2433750
Friedrich Reusswig, Olga An, Carsten Deppermann
{"title":"Platelet life cycle during aging: function, production and clearance.","authors":"Friedrich Reusswig, Olga An, Carsten Deppermann","doi":"10.1080/09537104.2024.2433750","DOIUrl":"10.1080/09537104.2024.2433750","url":null,"abstract":"<p><p>Platelets are important players in hemostasis. Alterations in platelet number and/or function lead to life-threatening conditions like thrombosis, myocardial infarction and stroke. During aging, changes at the cellular, organ and systemic level occur that affect platelet counts, platelet functionality, the expression of platelet surface receptors, clearance markers as well as their interactions with immune cells. Understanding how these changes influence platelets can help to prevent the alterations of hemostasis and thrombosis we observe in the elderly. In this review, we highlight the respective changes at important sites of the platelet life cycle: bone marrow, liver and spleen, but also show how alterations in immunity contribute. We point out the necessity for further research on age-related systemic alterations in these systems and their interplay with platelets to better understand the complex processes that cause alterations in the platelet life cycle during aging.</p>","PeriodicalId":20268,"journal":{"name":"Platelets","volume":"35 1","pages":"2433750"},"PeriodicalIF":2.5,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142771379","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}
PlateletsPub Date : 2024-12-01Epub Date: 2024-10-16DOI: 10.1080/09537104.2024.2415483
Monica Carpenedo, Arianna Zappaterra, Lorenzo Del Castello, Beatrice Ferrari, Giulia Cotilli, Davide Paolo Bernasconi, Sara Pezzatti, Filippo Sacco, Lorenza Borin, Andrea Carrer, Luisa Verga, Filippo Brioschi
{"title":"Feasibility and effectiveness of the prolonged use of eltrombopag in addition to immunosuppression in patients with acquired aplastic anemia: a single-center real-life experience.","authors":"Monica Carpenedo, Arianna Zappaterra, Lorenzo Del Castello, Beatrice Ferrari, Giulia Cotilli, Davide Paolo Bernasconi, Sara Pezzatti, Filippo Sacco, Lorenza Borin, Andrea Carrer, Luisa Verga, Filippo Brioschi","doi":"10.1080/09537104.2024.2415483","DOIUrl":"https://doi.org/10.1080/09537104.2024.2415483","url":null,"abstract":"<p><p>Acquired Aplastic Anemia (AAA) is a rare disease involving primary bone marrow failure with consequent pancytopenia. The addition of the synthetic thrombopoietin-receptor agonist eltrombopag (ELT) to standard immunosuppression for the treatment of AAA has led to improvements in hemopoietic outcomes of AAA. Most of the data on the use of ELT for AAA was based on a maximum of 6 months of therapy. However, in clinical practice, a longer use of ELT is often required. This paper presents a monocentric real-life experience with prolonged use of ELT in 10 patients with AAA, showing data on effectiveness and safety. In our cohort, a high rate of response to ELT added to standard immunosuppression in patients with varying grades of severity of AAA was reported. After a median (range) observation time of 47.5 (31-75) months, the treatment with ELT was feasible with an overall response probability of 70% and was not associated with any concerning adverse event. Two episodes of relapse were reported; no signs of evolution have been reported so far. In conclusion, ELT as a <i>dose-response-adjusted</i> prolonged therapy associated with standard immunosuppression in AAA patients not eligible for transplant seems to be feasible to consolidate and maintain the response.</p>","PeriodicalId":20268,"journal":{"name":"Platelets","volume":"35 1","pages":"2415483"},"PeriodicalIF":2.5,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142786669","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}
PlateletsPub Date : 2024-12-01Epub Date: 2024-05-20DOI: 10.1080/09537104.2024.2354833
Joanna-Marie Howes, Matthew T Harper
{"title":"Application of the Cellular Thermal Shift Assay (CETSA) to validate drug target engagement in platelets.","authors":"Joanna-Marie Howes, Matthew T Harper","doi":"10.1080/09537104.2024.2354833","DOIUrl":"10.1080/09537104.2024.2354833","url":null,"abstract":"<p><p>Small molecule drugs play a major role in the study of human platelets. Effective action of a drug requires it to bind to one or more targets within the platelet (target engagement). However, although <i>in vitro</i> assays with isolated proteins can be used to determine drug affinity to these targets, additional factors affect target engagement and its consequences in an intact platelet, including plasma membrane permeability, intracellular metabolism or compartmentalization, and level of target expression. Mechanistic interpretation of the effect of drugs on platelet activity requires comprehensive investigation of drug binding in the proper cellular context, i.e. in intact platelets. The Cellular Thermal Shift Assay (CETSA) is a valuable method to investigate target engagement within complex cellular environments. The assay is based on the principle that drug binding to a target protein increases that protein's thermal stability. In this technical report, we describe the application of CETSA to platelets. We highlight CETSA as a quick and informative technique for confirming the direct binding of drugs to platelet protein targets, providing a platform for understanding the mechanism of action of drugs in platelets, and which will be a valuable tool for investigating platelet signaling and function.</p>","PeriodicalId":20268,"journal":{"name":"Platelets","volume":"35 1","pages":"2354833"},"PeriodicalIF":2.5,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141064598","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}
PlateletsPub Date : 2024-12-01Epub Date: 2024-02-14DOI: 10.1080/09537104.2024.2315713
Kirk A Taylor
{"title":"Edi(torial) 2024: action plan for change and new initiatives.","authors":"Kirk A Taylor","doi":"10.1080/09537104.2024.2315713","DOIUrl":"10.1080/09537104.2024.2315713","url":null,"abstract":"","PeriodicalId":20268,"journal":{"name":"Platelets","volume":"35 1","pages":"2315713"},"PeriodicalIF":2.5,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139730373","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}
PlateletsPub Date : 2024-12-01Epub Date: 2024-02-22DOI: 10.1080/09537104.2024.2316745
Yan Wei, Yihong Cheng, Hongjiang Wei, Yulan Wang, Xiaoxin Zhang, Richard J Miron, Yufeng Zhang, Shanglan Qing
{"title":"Development of a super-hydrophilic anaerobic tube for the optimization of platelet-rich fibrin.","authors":"Yan Wei, Yihong Cheng, Hongjiang Wei, Yulan Wang, Xiaoxin Zhang, Richard J Miron, Yufeng Zhang, Shanglan Qing","doi":"10.1080/09537104.2024.2316745","DOIUrl":"https://doi.org/10.1080/09537104.2024.2316745","url":null,"abstract":"<p><p>Horizontal platelet-rich fibrin (H-PRF) contains a variety of bioactive growth factors and cytokines that play a key role in the process of tissue healing and regeneration. The blood collection tubes used to produce Solid-PRF (plasmatrix (PM) tubes) have previously been shown to have a great impact on the morphology, strength and composition of the final H-PRF clot. Therefore, modification to PM tubes is an important step toward the future optimization of PRF. To this end, we innovatively modified the inner wall surface of the PM tubes with plasma and adjusted the gas environment inside the PM tubes to prepare super-hydrophilic anaerobic plasmatrix tubes (SHAP tubes). It was made anaerobic for the preparation of H-PRF with the aim of improving mechanical strength and bioactivity. The findings demonstrated that an anaerobic environment stimulated platelet activation within the PRF tubes. After compression, the prepared H-PRF membrane formed a fibrous cross-linked network with high fracture strength, ideal degradation characteristics, in addition to a significant increase in size. Thereafter, the H-PRF membranes prepared by the SHAP tubes significantly promoted collagen synthesis of gingival fibroblast and the mineralization of osteoblasts while maintaining excellent biocompatibility, and advantageous antibacterial properties. In conclusion, the newly modified PRF tubes had better platelet activation properties leading to better mechanical strength, a longer degradation period, and better regenerative properties in oral cell types including gingival fibroblast and alveolar osteoblasts. It also improves the success rate of H-PRF preparation in patients with coagulation dysfunction and expands the clinical application scenario.</p>","PeriodicalId":20268,"journal":{"name":"Platelets","volume":"35 1","pages":"2316745"},"PeriodicalIF":3.3,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139932584","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}
PlateletsPub Date : 2024-12-01Epub Date: 2024-05-22DOI: 10.1080/09537104.2024.2353582
Scott J Denardo, Pavlos P Vlachos, Brett A Meyers, Reza Babakhani-Galangashi, Lin Wang, Zejin Gao, James E Tcheng
{"title":"Translating proof-of-concept for platelet slip into improved antithrombotic therapeutic regimens.","authors":"Scott J Denardo, Pavlos P Vlachos, Brett A Meyers, Reza Babakhani-Galangashi, Lin Wang, Zejin Gao, James E Tcheng","doi":"10.1080/09537104.2024.2353582","DOIUrl":"10.1080/09537104.2024.2353582","url":null,"abstract":"<p><p>Platelets are central to thrombosis. Research at the intersection of biological and physical sciences provides proof-of-concept for shear rate-dependent platelet slip at vascular stenosis and near device surfaces. Platelet slip extends the observed biological \"slip-bonds\" to the boundary of functional gliding without contact. As a result, there is diminished engagement of the coagulation cascade by platelets at these surfaces. Comprehending platelet slip would more precisely direct antithrombotic regimens for different shear environments, including for percutaneous coronary intervention (PCI). In this brief report we promote translation of the proof-of-concept for platelet slip into improved antithrombotic regimens by: (1) reviewing new supporting basic biological science and clinical research for platelet slip; (2) hypothesizing the principal variables that affect platelet slip; (3) applying the consequent construct model in support of-and in some cases to challenge-relevant contemporary guidelines and their foundations (including for urgent, higher-risk PCI); and (4) suggesting future research pathways (both basic and clinical). Should future research demonstrate, explain and control platelet slip, then a paradigm shift for choosing and recommending antithrombotic regimens based on predicted shear rate should follow. Improved clinical outcomes with decreased complications accompanying this paradigm shift for higher-risk PCI would also result in substantive cost savings.</p>","PeriodicalId":20268,"journal":{"name":"Platelets","volume":"35 1","pages":"2353582"},"PeriodicalIF":3.3,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141076553","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}
PlateletsPub Date : 2024-12-01Epub Date: 2024-02-05DOI: 10.1080/09537104.2024.2306983
Xiaoyu Chen, Yuhong Zhao, Yan Lv, Jue Xie
{"title":"Immunological platelet transfusion refractoriness: current insights from mechanisms to therapeutics.","authors":"Xiaoyu Chen, Yuhong Zhao, Yan Lv, Jue Xie","doi":"10.1080/09537104.2024.2306983","DOIUrl":"10.1080/09537104.2024.2306983","url":null,"abstract":"<p><p>Although there have been tremendous improvements in the production and storage of platelets, platelet transfusion refractoriness (PTR) remains a serious clinical issue that may lead to various severe adverse events. The burden of supplying platelets is worsened by rising market demand and limited donor pools of compatible platelets. Antibodies against platelet antigens are known to activate platelets through FcγR-dependent or complement-activated channels, thereby rapidly eliminating foreign platelets. Recently, other mechanisms of platelet clearance have been reported. The current treatment strategy for PTR is to select appropriate and compatible platelets; however, this necessitates a sizable donor pool and technical assistance for costly testing. Consolidation of these mechanisms should be of critical significance in providing insight to establish novel therapeutics to target immunological platelet refractoriness. Therefore, the purposes of this review were to explore the modulation of the immune system over the activation and elimination of allogeneic platelets and to summarize the development of alternative approaches for treating and avoiding alloimmunization to human leukocyte antigen or human platelet antigen in PTR.</p>","PeriodicalId":20268,"journal":{"name":"Platelets","volume":"35 1","pages":"2306983"},"PeriodicalIF":3.3,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139692708","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}
PlateletsPub Date : 2024-12-01Epub Date: 2024-02-12DOI: 10.1080/09537104.2024.2308635
Yujia Ye, Min Leng, Shengjie Chai, Lihong Yang, Longcheng Ren, Wen Wan, Huawei Wang, Longjun Li, Chaozhong Li, Zhaohui Meng
{"title":"Antiplatelet effects of the CEACAM1-derived peptide QDTT.","authors":"Yujia Ye, Min Leng, Shengjie Chai, Lihong Yang, Longcheng Ren, Wen Wan, Huawei Wang, Longjun Li, Chaozhong Li, Zhaohui Meng","doi":"10.1080/09537104.2024.2308635","DOIUrl":"10.1080/09537104.2024.2308635","url":null,"abstract":"<p><p>Carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) restricts platelet activation via platelet collagen receptor GPVI/FcRγ-chain. In this study, screening against collagen-induced platelet aggregation was performed to identify functional CEACAM1 extracellular domain fragments. CEACAM1 fragments, including Ala-substituted peptides, were synthesized. Platelet assays were conducted on healthy donor samples for aggregation, cytotoxicity, adhesion, spreading, and secretion. Mice were used for tail bleeding and FeCl<sub>3</sub>-induced thrombosis experiments. Clot retraction was assessed using platelet-rich plasma. Extracellular segments of CEACAM1 and A1 domain-derived peptide QDTT were identified, while N, A2, and B domains showed no involvement. QDTT inhibited platelet aggregation. Ala substitution for essential amino acids (Asp139, Thr141, Tyr142, Trp144, and Trp145) in the QDTT sequence abrogated collagen-induced aggregation inhibition. QDTT also suppressed platelet secretion and \"inside-out\" GP IIb/IIIa activation by convulxin, along with inhibiting PI3K/Akt pathways. QDTT curtailed FeCl<sub>3</sub>-induced mesenteric thrombosis without significantly prolonging bleeding time, implying the potential of CEACAM1 A1 domain against platelet activation without raising bleeding risk, thus paving the way for novel antiplatelet drugs.</p>","PeriodicalId":20268,"journal":{"name":"Platelets","volume":"35 1","pages":"2308635"},"PeriodicalIF":3.3,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139723746","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}