A bibliometric and visual analysis of immune thrombocytopenia-associated macrophages

A bibliometric and visual analysis of immune thrombocytopenia-associated macrophages | Authorea try { document.documentElement.classList.add('js'); } catch (e) { } var _gaq = _gaq || []; _gaq.push(['_setAccount', 'G-8VDV14Y67G']); _gaq.push(['_trackPageview']); (function() { var ga = document.createElement('script'); ga.type = 'text/javascript'; ga.async = true; ga.src = ('https:' == document.location.protocol ? 'https://ssl' : 'http://www') + '.google-analytics.com/ga.js'; var s = document.getElementsByTagName('script')[0]; s.parentNode.insertBefore(ga, s); })(); Skip to main content Preprints Collections Wiley Open Research IET Open Research Ecological Society of Japan All Collections About About Authorea FAQs Contact Us Quick Search anywhere Search for preprint articles, keywords, etc. Search Search ADVANCED SEARCH SCROLL This is a preprint and has not been peer reviewed. Data may be preliminary. 25 February 2025 V1 Latest version Share on A bibliometric and visual analysis of immune thrombocytopenia-associated macrophages Authors : Xiaoyuan Fan [email protected] , Mingwei Li , Yunfei Zhang , Hongjie Jiao , Yingbin Yue , and Mei Yan Authors Info & Affiliations https://doi.org/10.22541/au.174048686.69120660/v1 255 views 174 downloads Contents Abstract Supplementary Material Information & Authors Metrics & Citations View Options References Figures Tables Media Share Abstract Background: Immune thrombocytopenia (ITP) is an autoimmune disorder associated with hemorrhagic diathesis, attributed to excessive platelet destruction or impaired generation. Macrophages are pivotal in ITP, yet their precise mechanisms remain incompletely understood. Objective: Using bibliometric and visual analytical methods, this study aims to sort out and analyze the research progress of ITP-associated macrophages over the past two decades to uncover the topical and evolving currents in the area. Methods: Utilizing software including CiteSpace, VOSviewer, Scimago Graphica, and Microsoft Excel, we conducted a quantitative analysis of literature retrieved from the Web of Science Core Collection database, encompassing January 1, 2005, to October 18, 2024. Results: 1,025 documents were screened, involving 6,896 authors from 1,832 institutions across 78 countries, published in 433 journals. The annual publication trend from 2005 to 2021 demonstrated an upward trajectory, with a notable increase post-2020. The United States and China are the most critical nations contributing to this subject. Prominent authors include Hou, Ming, and Arepally, GM, with critical journals such as Blood and the Journal of Thrombosis and Haemostasis. Co-occurrence network analysis of keywords revealed research foci on inflammatory responses, autoimmune diseases, and platelet coagulation mechanisms. Conclusion: Research on macrophages related to ITP has made significant strides Over the preceding 20 years, particularly in unearthing the mechanisms underlying macrophage activity in ITP. This study establishes a systematic framework for work endeavors and indicates potential therapeutic targets and emerging trends. –Title Page– A bibliometric and visual analysis of immune thrombocytopenia-associated macrophages Authors: Xiaoyuan Fan, E-mail: [email protected] Mingwei Li, E-mail: [email protected] Yunfei Zhang, E-mail: [email protected] Hongjie Jiao, E-mail: [email protected] Yingbin Yue, E-mail: [email protected] Mei Yan *, E-mail: [email protected] Department of Pediatrics, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang, 830054, China *Correspondence author: Mei Yan E-mail: [email protected] Address: Department of Pediatrics, The First Affiliated Hospital of Xinjiang Medical University, 393 Xinyi Rd. Urumqi, Xinjiang, 830054, China Funding: This work was supported by the Mechanism of Echinococcus Antigen B in Regulating Macrophage Polarization to Alleviate Immune Thrombocytopenia (82160031); Basic Research on Pediatric Severe Diseases, Cohort Studies of Specific Diseases, and Construction of Early Warning Models (2024B03038-1); Exploration of Etiology and Prognostic Prediction Cohort Study of Pediatric Immune Thrombocytopenia, and Application and Promotion (TSYC202301A002). A bibliometric and visual analysis of immune thrombocytopenia-associated macrophages Abstract Background: Immune thrombocytopenia (ITP) is an autoimmune disorder associated with hemorrhagic diathesis, attributed to excessive platelet destruction or impaired generation. Macrophages are pivotal in ITP, yet their precise mechanisms remain incompletely understood. Objective: Using bibliometric and visual analytical methods, this study aims to sort out and analyze the research progress of ITP-associated macrophages over the past two decades to uncover the topical and evolving currents in the area. Methods: Utilizing software including CiteSpace, VOSviewer, Scimago Graphica, and Microsoft Excel, we conducted a quantitative analysis of literature retrieved from the Web of Science Core Collection database, encompassing January 1, 2005, to October 18, 2024. Results: 1,025 documents were screened, involving 6,896 authors from 1,832 institutions across 78 countries, published in 433 journals. The annual publication trend from 2005 to 2021 demonstrated an upward trajectory, with a notable increase post-2020. The United States and China are the most critical nations contributing to this subject. Prominent authors include Hou, Ming, and Arepally, GM, with critical journals such as Blood and the Journal of Thrombosis and Haemostasis. Co-occurrence network analysis of keywords revealed research foci on inflammatory responses, autoimmune diseases, and platelet coagulation mechanisms. Conclusion: Research on macrophages related to ITP has made significant strides Over the preceding 20 years, particularly in unearthing the mechanisms underlying macrophage activity in ITP. This study establishes a systematic framework for work endeavors and indicates potential therapeutic targets and emerging trends. Keywords Immune Thrombocytopenia, Macrophages, Bibliometrics, Visual Analysis, Research Trends 1 Introduction Immune thrombocytopenia (ITP) is an autoimmune hemorrhagic disorder invoked by persistent thrombocytopenia, typically attributed to increased platelet destruction or diminished platelet production [1,2]. Epidemiological studies have indicated an overall annual incidence of ITP ranging from 3 to 4 cases per 100,000 individuals, with a slightly higher rate in children than adults [3,4]. Approximately 80-90% of pediatric patients with ITP exhibit a self-limited course [5], whereas most adult patients progress to a chronic disease course [6]. Around 10% of patients develop refractory ITP due to poor response to treatment or treatment failure [7], which significantly impairs their quality of life and increases the risk of mortality [8,9]. Therefore, delving into the pathogenesis of ITP is of paramount importance for updating and optimizing therapeutic strategies, as well as for guiding the formulation of treatment plans. Macrophages are a core component of antimicrobial host defense [10] and polarize into two phenotypes depending on the local tissue environment when stimulated by different cytokines: Classically activated M1 macrophages and alternatively activated M2 macrophages [11,12], respectively, play specific immunomodulatory functions. M1 macrophages are crucial for clearing pathogens, initiating immune responses, and promoting Th1-type immune responses, and have pro-inflammatory effects. M2 macrophages can foster cell proliferation, facilitate tissue repair, and exhibit anti-inflammatory properties [13,14]. This flexible polarization ability allows macrophages to adapt to a variable immune environment and perform diverse biological functions [10,15,16]. Recently, research has demonstrated that the quantity of M2 macrophages is significantly elevated in ITP patients following effective pharmacological intervention, and in vitro experiments of the same study also observed an enhanced chemotactic activity of macrophages polarizing towards the M2 direction under drug intervention [17]. Conversely, the polarization and migration of M1 macrophages exacerbate the progression of ITP, not only promoting Fcγ receptor (FcγR)-mediated phagocytosis, leading to an increased platelet clearance rate but also participating in the production of B cell-dependent anti-platelet autoantibodies [18]. Therefore, elucidating the molecular mechanisms of macrophages in ITP and the interactions between macrophages and other cells is significant for advancing innovative targeted therapeutic approaches and effectively monitoring treatment outcomes. It is challenging for new researchers in this field to identify the correct developmental mainline and research frontier from the complex status quo of research. Hence, this article employs bibliometric and visualization analysis methods, starting from research hotspots (keyword relationship networks) and development paths (timeline diagrams), to comprehensively sort and analyze the research progress of ITP over the past decade. It quantitatively presents the research focus and recent development trends in this field. The article mainly focuses on the following issues: 1. Which major organizations are focusing on the study of macrophages in ITP? 2. Which journals mainly published research papers on ITP-related macrophages? 3. What are the prevalent keywords in the literature on ITP-associated macrophages? What’s the connection? 2 Methodology and Data Source 2.1 Methodology Bibliometrics, an interdisciplinary domain integrating mathematical and statistical methodologies, enables researchers to quantitatively analyze existing literature’s volume, quality, citation patterns, and interrelations. This analysis aids in understanding the current state and trends within specific domains [19,20]. Visualization techniques are crucial in bibliometrics, particularly when managing vast data. These techniques intuitively present analysis results through charts and graphics, highlighting critical information such as the evolution, status, hotspots, and trends of research topics. This visual representation allows readers to quickly and clearly grasp the meaning of the data and discern the intrinsic connections between pieces of information [21]. This study used tools including CiteSpace, VOSviewer, Scimago Graphica, and Microsoft Excel for bibliometric analysis and charting. CiteSpace (version 6.2.R2) employed co-citation analysis to generate cluster views and timeline diagrams of keywords and references using similarity algorithms, thereby visually depicting the development process and research trends in the field over time [21]. VOSviewer (version 1.6.20) utilized a probabilistic data normalization method to display co-occurrence networks and density views of countries/regions, organizations, authors, journals, references, and keywords, revealing the research structure and focal points within the field [22]. Scimago Graphica (version 1.0.42) was employed to map the number of publications and collaborative relationships on a world map, showcasing the global research collaboration landscape and the geographical distribution of publications [23]. Microsoft Excel (version 16.90) was used to compile and organize the extracted information, as well as to plot publication trend graphs and lists. 2.2 Date Sources The Web of Science Core Collection (WoSCC) database is a comprehensive academic citation index database that includes over 20,000 high-quality, reliable academic journals across multidisciplinary. It is widely used for academic research and bibliometric analysis. Therefore, this study selected the WoSCC as the data retrieval source, with the Science Citation Index Expanded (SCI-EXPANDED) as the citation index, to ensure the authority and academic value of the retrieved data, aiming to provide the highest quality evidence to support the research. The search strategy was TS= ((”Immune Thrombocytopenia” OR ”Primary Immune Thrombocytopenia” OR ”Immune Thrombocytopenia Syndrome” OR ”Idiopathic Thrombocytopenic Purpura” OR ”Immune Thrombocytopenia Purpura” OR Thrombocytopenia OR ITP) AND (macrophage OR macrophages OR monocyte OR monocytes)), with publication dates ranging from January 1, 2005, to October 18, 2024, limited to the English language, and excluding article types other than ”Article” and ”Review”. Duplicate and off-topic content were screened and removed. To minimize the risk of errors associated with database updates and individual subjectivity, three team members searched independently and simultaneously on October 18, 2024. After reaching a consensus, we retrieved 1025 documents, which included 892 articles and 133 reviews (Fig. 1). 2.3 Data extraction Following the search strategy (Table 1), the 1,025 retrieved documents were exported and saved in a folder in plain text format as ”Full Record and Cited References”. Information on publications, countries/regions, organizations, authors, journals, keywords, and references (including co-citation information) was collected. Subsequently, the ”Citation Report” was accessed to obtain the Hirsch index (H-index) for authors and countries. All journal-related data, including the Impact Factor (IF) and Category Quartile, were derived from the most recent data available in the Journal Citation Report (JCR) for the year 2023. 3 Result 3.1 Analysis of annual publication trends The number of publications across different periods primarily reflects the general trends in research activities within a field, providing the academic community with quantitative indicators of research hotspots and developmental directions. 1,025 articles were selected for analysis, authored by 6,896 researchers from 1,832 organizations across 78 countries, published in 433 journals, and citing 36,094 references from 4,906 journals. Fig. 2 shows the temporal distribution of publications concerning ITP-associated macrophage research. Overall, from 2005 to 2021, the annual publication output showed a gradually upward trend, peaking in 2021 with 8.78% of the total publications, nearly triple that of the figure in 2005. Compared to 2021, the global COVID-19 pandemic has led to a slight decline in publications in the last two years, yet still significantly higher than before. The number of publications from 2020 to 2024 is 361, which is more than one-third of the total, suggesting that this field has increasingly received attention and widespread academic interest over the past five years. 3.2 Analysis of countries/regions and organizations We constructed a world map that integrates publication country information and inter-country collaborative relationships, visually representing the interconnectedness of global academic research (Fig. 3). The collaboration among the United States, China, and Canada is particularly significant (Fig. 4a). As listed in Table 2, the countries/regions with the highest publication output are predominantly situated in Europe (5), North America (2), and Asia (2), with the United States at the forefront with 30.34%, followed by China at 20.68%, significantly surpassing other nations. Notably, although Asian countries (China and Japan) have a higher volume of publications (29.56%), their average citation rates are less favorable in comparison. In contrast, despite not having standout publication numbers, European countries/regions such as England and the Netherlands have average citation rates above 60 times per article, with England exceptionally high at 69.00 times. A comprehensive analysis of publication volume, average citations per article, and H-index [24] indicates that the United States contributes the most academically to this field (Fig. 4b). Among the top ten organizations (Table 3), the University of Toronto led with the most excellent volume of publications (35), trailed by Shandong University in China (27) and the University of Pennsylvania in the United States (24). Remarkably, INSERM, despite publishing only 16 publications, had an impressive average citation rate of 104.19, indicating a high quality of research output that merits scholarly attention. Employing VOSviewer, a collaboration network map was generated (Fig. 5a). Each node stands for an organization, with the thickness of the lines interconnecting nodes reflecting the extent of partnerships. Moreover, the size of each node is directly proportional to the publication output of the corresponding organization. The University of Toronto had a significantly higher link strength than others, suggesting extensive scholarly exchanges with other organizations. Lately, as this field continues to develop and mature, organizations including China’s Wuhan University, Fudan University, and Zhengzhou University, along with Germany’s Justus Liebig University Giessen, have been augmenting their research contributions and engaging more actively in international collaborative efforts (Fig. 5b). 3.3 Analysis of authors and co-cited authors Examining authors’ output can expedite the identification of critical academic representatives and principal research contributors within the field. The renowned scholar Price [25] noted that in a subject area, nearly half of the publications are attributed to a cohort of prolific authors, the size of which is roughly equivalent to the square root of the overall author count. In line with Price’s Law [25], this corresponds to the minimum number of publications (m=0.749\(\sqrt{n\text{max}}\)≈3.00, VOSviewer statistics show that n max =16) required for an author to be considered a core contributor within the field. Therefore, 168 authors with a publication count of three or more (including three) were identified as core contributors in this discipline, accounting for 668 publications, which represents 65.17% of the total output, meeting the half standard. This suggests that the research on ITP-related macrophages has formed a sufficiently stable group of collaborating scholars. Table 4 lists the 10 leading authors regarding productivity in this research domain, with Hou Ming from Shandong University in China being the most prolific. Between 2005 and 2024, Hou Ming authored 16 ITP and macrophage research articles, which have received an average citation frequency of 36.75 per publication. Furthermore, Hou Ming possesses the highest H-index and total citation count, signifying a substantial impact in the field. Arepally, GM, affiliated with Duke University in the United States, holds the most extensive citation record, averaging 62.38 citations per article. However, the author collaboration contribution network (Fig. 6a) shows these two core authors have yet to collaborate. Increased international collaboration should be pursued to provide patients with safer and more effective treatment options and offer valuable direction for upcoming research and clinical practice in this field. When the research outputs of two scholars are frequently co-cited in subsequent studies, it suggests a correlation between their research fields or academic perspectives. In such cases, co-citation analysis can be employed to reveal the academic connections between the two scholars [26]. Using VOSviewer with a minimum citation threshold of 27 times, a network map was generated consisting of 60 highly co-cited authors (Fig. 6b), with authors in the same cluster exhibiting a high degree of relevance. The green cluster, centered around Warkentin, TE, Greinacher, A, and Cines, DB, focuses on the study of anti-platelet factor 4 (PF4) immune diseases, such as heparin-induced thrombocytopenia (HIT) and vaccine-induced immune thrombotic thrombocytopenia (VITT) [27,28,29]. These three authors also top the list of the most co-cited authors (Table 5) and have made outstanding contributions to the field. The red cluster, centered around Semple, JW, Kuwana, M, and Crow, AR, focuses on studying ITP immune mechanisms and immune support therapies (such as IVIG and antibodies) [30,31,32]. The blue cluster, centered around Henter, JI, and Ravelli, A, focuses on the study of the diagnosis and treatment of autoimmune rheumatic diseases such as Hemophagocytic lymphohistiocytosis (HLH)/ macrophage activation syndrome (MAS) and juvenile idiopathic arthritis (JIA) [33,34]. The purple cluster, centered around Nomura, S, and George, JN, focuses on studying macrophage-related marker protein and cytokine expression in ITP and thrombotic thrombocytopenic purpura (TTP) [35,36,37,38]. 3.4 Analysis of journals and co-cited journals After statistical analysis of the journals to which the literature belongs, it was found that 433 journals published research related to ITP and macrophages, with the majority being specialized in hematology. Table 6 ranks the top ten journals by article publication volume in this field, with Blood leading the list, followed by Transfusion and the Journal of Thrombosis and Haemostasis. According to the 2023 Journal Citation Reports, among these 10 journals, 6 have an Impact Factor (IF) exceeding 5.0 (including 5.0), with Blood being the most influential, having an IF of 21.0 and an average citation rate of 77.98 times per article. This fully demonstrates Blood’s important position in the field and its wide recognition, providing scholars with an authoritative platform for showcasing their research and academic exchange. Fig. 7a is a contribution network map of 46 journals with at least 5 published articles. From the figure, Blood, and Journal of Thrombosis and Haemostasis have noticeably stronger links and larger nodes than surrounding journals. Combined with Table 6, it is evident that these two journals also have the highest average citation rates, indicating that they have broader collaborative relationships with other journals and make more remarkable contributions to the field. Analyzing co-cited journals aids scholars in assessing the importance and impact of academic journals, and in precisely identifying and selecting journals with higher academic value [39]. Table 7 presents the top ten co-cited journals, ordered by decreasing citation frequency. Notably, 80% of these journals are classified as prestigious JCR Q1 category publications. Among them, The New England Journal of Medicine ranked fourth and stands out as a leading journal in the medical field with an IF of 96.2. Blood ranks as the journal with the most significant citation impact, garnering 4,418 citations, followed by the Journal of Immunology, with 1,092 citations, and the British Journal of Haematology, with 985 citations. The co-citation network of journals comprises three main cluster categories (Fig. 7b): the blue cluster centered on Blood focuses on publishing clinical and experimental research articles related to hematological diseases [40,41], the red cluster centered on the Journal of Immunology mainly covers articles in various fields of experimental immunology and serves as a primary reference source for research methods related to ITP and macrophages [42,43], and the green cluster centered on the Journal of Thrombosis and Haemostasis mainly focuses on scientific research concerning the role of macrophages in thrombosis, hemostasis, inflammation, and immune modulation [44,45]. Citing these journals primarily assesses prior research and offers theoretical and empirical backing for the research in question. 3.5 Analysis of highly cited references Table 8 lists the ten most highly cited references in this research domain, published between 2001 and 2011, with the majority being article types. Seven of these papers have garnered citations exceeding 30 times. The most frequently cited paper is ”HLH-2004: Diagnostic and therapeutic guidelines for hemophagocytic lymphohistiocytosis,” authored by Henter JI et al., published in Pediatric Blood Cancer (Fig. 8a). ITP and HLH both involve excessive activation of the immune system, with certain similarities, particularly in the activation and functional manifestations of macrophages. Therefore, this guideline should inspire ITP-related macrophage research, such as how macrophages participate in the clearance of platelets and how to regulate the activity of macrophages with new ideas. Additionally, there are two high-quality papers published in The New England Journal of Medicine (IF=96.2), one by Yu XJ et al. from China, who discovered a novel bunyavirus associated with Severe Fever with Thrombocytopenia Syndrome (SFTS) and one the other by Cines DB et al., who provided a comprehensive review of the pathophysiology, diagnostic criteria, clinical manifestations, and treatment strategies of ITP, an essential resource for research in this field. Fig. 8b depicts the top 20 most prominent references, with the blue and red lines collectively representing the timeline of citation bursts for these references. The lighter portion of the blue line indicates periods where the references have yet to emerge, while the darker section signifies the presence of references with relatively fewer citation frequencies. The red line segments denote the periods during which the references have exhibited the strongest sustained emergence. The figure shows citation burst strengths of 3.69-6.96 in the recent five years, with Crayne CB et al.’s study having the most extended high-strength period (2020-2024). This review article comprehensively discusses the immunological mechanisms of Macrophage Activation Syndrome (MAS), including its association with systemic immune-mediated diseases such as Systemic Juvenile Idiopathic Arthritis (sJIA) and Systemic Lupus Erythematosus (SLE), as well as the clinical manifestations, pathophysiology, diagnostic criteria, and therapeutic strategies for MAS. 3.6 Keywords cluster and timeline analysis The frequency and co-occurrence relationships of keywords reflect the popular topics and trends in the field, aiding scholars in rapidly comprehending the knowledge structure of the domain [46]. Among the 4949 keywords, 93 keywords with a frequency threshold of at least 15 occurrences were extracted, similar keywords were merged, and a co-occurrence network map was created with VOSviewer. Graphed in Fig. 9a, the red cluster contains 45 keywords, primarily related to cell biology and signal transduction studies associated with inflammatory responses, such as ”tumor necrosis factor”, ”colony-stimulating factor”, and ”lymphocytes”. The green cluster comprises 27 keywords, mainly related to clinical research and application guidelines for autoimmune diseases, such as ”juvenile idiopathic arthritis”, ”rheumatoid arthritis”, and ”immune thrombocytopenia”. The blue cluster includes 21 keywords, primarily associated with hematological diseases related to platelets and coagulation mechanisms, such as ”thrombocytopenia” and ”hemophagocytic lymphohistiocytosis”. To elucidate the academic concentration within this domain, a keyword density map was constructed (Fig. 9b). The color shade corresponds to the prevalence of keywords, highlighting high-frequency terms such as ”thrombocytopenia”, ”expression”, ”activation”, ”immune thrombocytopenia”, and ”macrophages” as the field’s representative terminology. Fig. 10a is a keyword timeline generated using the Citespace algorithm, which delineates the frequency and trends of keyword emergence across different periods. Further analysis of keyword emergence reveals that Fig. 10b displays the top 20 keywords with the highest burst frequencies. It can be observed that early high-frequency keywords related to macrophage and ITP research mainly focused on ”idiopathic thrombocytopenic purpura”, ”intravenous immunoglobulin”, ”in vitro”, ”cells”, and ”antibody”. Current research frontiers include ”management”, ”monocytes,” and ”pathogenesis”. Overall, the hotspot with the most prolonged duration is ”intravenous immunoglobulin” (2005-2014), while the most intense burst was for ”disease”, reaching a peak strength of 8.52 between 2011 and 2014. 4 Conclusion This systematic review employs bibliometric methods to analyze research trends in immune thrombocytopenia (ITP)-associated macrophages. Key findings include: • Publication Trends: Annual output progressed through three phases: initial (2005–2009, limited activity), gradual growth (2010–2020), and rapid expansion (2020–2024, 35% of total publications). • Geographical Distribution: The U.S. dominated contributions (30.34% of publications, H-index=65, total link strength=214), with high citation impact (51.85 citations/paper). Asian nations (China [2nd], Japan [3rd]) showed productivity-citation disparities, reflecting regional developmental gaps. • Institutional Contributions: U.S. institutions comprised 40% of the top 10 productive organizations, correlating with robust research investment. University of Toronto led publication volume with extensive collaborations. INSERM achieved exceptional citation rates (>100/paper). Chinese institutions (Wuhan University, Fudan University) demonstrated growing international engagement. • Author Networks: Hou Ming and Arepally GM emerged as core authors. Co-citation analysis identified four thematic clusters, indicating specialized research directions. • Journal Impact: 60% of the top 10 journals had IF≥5.0. Blood (IF=21.0) ranked first in publications (77.98 citations/article) and co-citation frequency. Key platforms included the Journal of Immunology and the New England Journal of Medicine. • Seminal Works: Highly cited papers have laid a solid theoretical foundation and provide significant background support for subsequent research [47]. Top-cited papers (2001–2011) focused on ITP guidelines (4/10) and pathophysiology/therapy (4/10). The landmark citation (Henter et al., 2007) addressed HLH, offering mechanistic parallels to ITP macrophage activation despite clinical differences[48,49,50,51]. • Research Frontiers: Keyword clustering revealed a predominant focus on inflammatory signaling pathways. Recent trends emphasize monocyte biology, disease management, and pathogenesis mechanisms. 5 Practical implications The severity of ITP is reflected in the risk of bleeding and its profound impact on patients’ quality of life, emotions, social activities, and long-term health management [52,53,54]. Therefore, intensifying research on ITP is of great significance for improving diagnostic and therapeutic levels, enhancing patients’ quality of life, reducing medical costs, and promoting the development of new drugs. From the perspective of bibliometrics and scientometrics, this article meticulously combs the developmental context of ITP-related macrophage research, constructing a systematic framework for scholars. It deepens their understanding of the field and promotes the deepening of research work. Furthermore, clustering and analyzing the evolution of high-frequency keywords reveals the focus and hot issues in ITP-related macrophage research, providing valuable references and guidance for scholars in determining research topics. This helps them grasp research trends and optimize research directions. The details are as follows： • Pathogenic Mechanism Research: Investigate the pathological role of macrophages in ITP, including their involvement in the destruction and clearance of platelets—for instance, research on how macrophages participate in the pathogenesis of ITP through FcγR signaling. • Macrophage Subset Research: Explore the distribution and function of macrophage subsets in ITP patients, such as the proportion and polarization status of M1 and M2 macrophages, and their roles in the disease. • Cytokines and Signaling Pathways: Study the cytokines secreted by macrophages in ITP, such as IL-6, and TNF-α, and how they affect macrophage polarization and function. • Therapeutic Response Research: Analyze the role of macrophages in ITP treatment, particularly their response to glucocorticoid therapy, and how modulating macrophage activity can improve therapeutic outcomes. • Molecular Mechanism Research: Explore the molecular mechanisms of macrophages in ITP, including the role of gene expression, epigenetic modifications, and non-coding RNA in macrophage polarization and function. • Macrophage Polarization Regulation: Examine the governing mechanisms of macrophage polarization, including the role of signaling pathways such as JAK/STAT NF-κB in macrophage polarization, and how modulating these pathways can control inflammatory responses and promote tissue repair. • Exploration of New Therapeutic Targets: Based on our understanding of macrophages’ role in ITP, we will explore new therapeutic targets, such as MST4 kinase, which plays a crucial role in regulating M1 macrophage polarization and may become a potential therapeutic target for refractory ITP. • Clinical Research and Case Analysis: Through clinical research and case analysis, understand the actual situation of macrophages in ITP patients and their relationship with disease severity, treatment response, and prognosis. • Immunomodulation Research: As a core component in maintaining tissue homeostasis, wound healing, muscle regeneration, and limb regeneration, the role of macrophages in immunomodulation is also one of the hot topics of research. This study conducted an in-depth analysis of the top journals and core author groups in ITP-related macrophages, facilitating scholars’ efficient retrieval of literature relevant to their research topics. Additionally, these analytical results have, to a certain extent, indicated suitable journal options for scholars when submitting papers in this field, thereby enhancing the pertinency and success rate of paper publication. 6 Limitations We utilized various bibliometric tools to represent the research on ITP-related macrophages visually, dissecting the research dynamics in the field from multiple perspectives to guarantee the comprehensiveness and objectivity of the study results. Admittedly, this study is subject to certain constraints. Firstly, the research data was sourced solely from the WoSCC (SCI-EXPANDED) database. Although this is a globally recognized and authoritative database that provides a certain degree of global perspective, it may only cover some relevant literature, and there is a possibility of data omission in the collection. Secondly, our study was limited to publication types and language. While this type of literature already has sufficient influence and representativeness in the field, it may need to include a few significant research findings. Fundings This work was supported by the Mechanism of Echinococcus Antigen B in Regulating Macrophage Polarization to Alleviate Immune Thrombocytopenia (82160031); Basic Research on Pediatric Severe Diseases, Cohort Studies of Specific Diseases, and Construction of Early Warning Models (2024B03038-1); Exploration of Etiology and Prognostic Prediction Cohort Study of Pediatric Immune Thrombocytopenia, and Application and Promotion (TSYC202301A002). Ethics approval and consent to participate Not applicable. Data availability statement All data generated or analyzed during this study are included in this article. Author contributions Xiaoyuan Fan: Writing – original draft, Investigation, Visualization, Formal analysis, Data curation. Mingwei Li: Investigation, Conceptualization, Validation, Formal analysis, Data curation. Yunfei Zhang: Software, Project administration. Hongjie Jiao: Methodology, Project administration. Yingbin Yue: Project administration. Mei Yan: Writing – review & editing, Supervision, Funding acquisition. Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. Acknowledgements Not applicable. References 1. 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Hematology. 2021 Dec;26(1):465-472. doi: 10.1080/16078454.2021.1945236. 54. Neunert CE, Buchanan GR, Blanchette V, Barnard D, Young NL, Curtis C, Klaassen RJ. Relationships among bleeding severity, health-related quality of life, and platelet count in children with immune thrombocytopenic purpura. Pediatr Blood Cancer. 2009 Oct;53(4):652-4. doi: 10.1002/pbc.21978. Fig. 1 Publication search and screening process. Fig. 2 Annual publication and cumulative annual output of ITP-associated macrophage research. Fig. 3 World map of publications countries and partnerships. Fig. 4 (a) International collaborative partnerships. (b) Academic contributions of various countries in ITP-associated macrophage research. Fig. 5 (a) Inter-organizational collaboration. (b) Organizational temporal evolution network graph. Fig. 6 (a) Author collaboration network in ITP- associated macrophage research. (b) Co-citation network map of 60 highly co-cited authors. Fig. 7 (a) Contribution network graph of 46 journals with five or more publications. (b) Visual co-citation network of journals in ITP-associated macrophage research. Fig. 8 (a) VOSviewer-generated visualization map of bibliographic co-cited. (b) Citespace-generated top 20 bursty cited references. Fig. 9 (a) VOSviewer-generated keyword co-occurrence network map. (b) VOSviewer-generated keyword density visualization. Fig. 10 (a) Citespace-generated keyword timeline visualization. (b) Citespace-generated top 20 burst keywords. Table 1 Summary of data source and selection Research database Web of Science Core Collection（WoSCC） Citation indexes Science Citation Index Expanded（SCI-EXPANDED） Searching period 1 January 2005 to 18 October 2024 Language English Searching Keywords (”Immune Thrombocytopenia” OR ”Primary Immune Thrombocytopenia” OR ”Immune Thrombocytopenia Syndrome” OR ”Idiopathic Thrombocytopenic Purpura” OR ”Immune Thrombocytopenia Purpura” OR Thrombocytopenia OR ITP) AND (macrophage OR macrophages OR monocyte OR monocytes) Main subject categories Medicine Document types Article and Review Data extraction Export with full record and cited references in plain text file Sample size 1025 Table 2 Top 10 countries with publications in ITP-associated macrophage research 1 USA North America 311 30.34 16126 51.85 65 214 2 China Asia 212 20.68 5099 24.05 32 68 3 Japan Asia 91 8.88 1738 19.10 24 34 4 Germany Europe 70 6.83 3169 45.27 28 87 5 Canada North America 69 6.73 3276 47.48 27 82 6 France Europe 64 6.24 3615 56.48 31 63 7 England Europe 56 5.46 3864 69.00 28 86 8 Italy Europe 53 5.17 1864 35.17 22 44 9 Brazil South America 49 4.78 1097 22.39 17 28 10 Netherlands Europe 44 4.29 2668 60.64 28 60 Table 3 Top 10 institutions with publications in ITP-associated macrophage research 1 University of Toronto 35 Canada 1070 30.57 65 2 Shandong University 27 China 782 28.96 32 3 University of Pennsylvania 24 USA 1490 62.08 35 4 Canadian Blood Services 21 Canada 768 36.57 46 5 Children’s Hospital of Philadelphia 18 USA 1400 77.78 41 6 Duke University 18 USA 775 43.06 25 7 INSERM 16 France 1667 104.19 12 8 Chinese Academy of Medical Sciences 15 China 745 49.67 22 9 St. Michael’s Hospital 15 Canada 728 48.53 35 10 University of Pittsburgh 15 USA 412 27.47 24 Table 4 Top 10 authors with publications in ITP-associated macrophage research 1 Hou, Ming Shandong University China 16 588 36.75 10 30 2 Peng, Jun Shandong University China 15 559 37.27 10 28 3 Cines,DB University of Pennsylvania USA 11 366 33.27 10 26 4 Lazarus, AH University of Toronto Canada 11 350 31.82 8 6 5 Branch, DR University of Toronto Canada 10 171 17.10 7 2 6 Poncz, M University of Pennsylvania USA 10 413 41.30 9 26 7 Rauova, L University of Pennsylvania USA 10 413 41.30 9 26 8 Arepally, GM Duke University USA 8 499 62.38 8 15 9 Hou, Yu Shandong University China 8 122 15.25 6 20 10 Santoso, S Justus-Liebig University Giessen Germany 8 169 21.13 6 0 Table 5 Top 10 co-cited authors with publications in ITP-associated macrophage research 1 Warkentin, TE McMaster University Canada 261 2 Greinacher, A Ernst Moritz Arndt University of Greifswald Germany 146 3 Cines, DB University of Pennsylvania USA 135 4 Semple,JW Lund University Sweden 121 5 Kuwana, M Nippon Medical School Japan 116 6 Henter, JI Karolinska University Sweden 92 7 Crow, AR University of Toronto Canada 90 8 Mcmillan, R The Scripps Research Institute USA 79 9 Audia, S University of Bourgogne/Franche-Comté France 72 10 Bussel, JB Weill Cornell Medicine USA 72 Table 6 Top 10 journals with publications in ITP-associated macrophage research 1 Blood 47 3665 77.98 21.0 Q1 180 2 Transfusion 22 332 15.09 2.5 Q2 38 3 Journal of Thrombosis and Haemostasis 18 564 31.33 5.5 Q1 74 4 Veterinary Clinical Pathology 17 186 10.94 1.2 Q3 7 5 British Journal of Haematology 16 420 26.25 5.1 Q1 30 6 Frontiers in Immunology 16 499 31.19 5.7 Q1 56 7 Plos One 15 295 19.67 2.9 Q1 14 8 Thrombosis and Haemostasis 15 362 24.13 5.0 Q1 57 9 Platelets 14 236 16.86 2.5 Q2 25 10 Blood Advances 13 219 16.85 7.4 Q1 33 Table 7 Top 10 co-cited journals with publications in ITP-associated macrophage research 1 Blood 4418 21.0 Q1 142306 2 Journal of Immunology 1092 3.6 Q2 38627 3 British Journal of Haematology 985 5.1 Q1 40515 4 The New England Journal of Medicine 876 96.2 Q1 30655 5 Journal of Thrombosis and Haemostasis 687 5.5 Q1 31761 6 Thrombosis and Haemostasis 677 5.0 Q1 31218 7 Proceedings of the National Academy of Sciences of the United States of America 590 9.4 Q1 22366 8 The Journal of Clinical Investigation 581 13.3 Q1 23891 9 Journal of Biological Chemistry 529 4.0 Q2 19253 10 Journal of Experimental Medicine 500 12.6 Q1 19691 Table 8 Top 10 cited papers with publications in ITP-associated macrophage research 1 Henter JI. et al. HLH-2004: Diagnostic and therapeutic guidelines for hemophagocytic lymphohistiocytosis. Pediatr Blood Cancer. 2007 Feb;48(2):124-31. doi: 10.1002/pbc.21039. 2007 57 2.4 Review 2 Rodeghiero F. et al. Standardization of terminology, definitions and outcome criteria in immune thrombocytopenic purpura of adults and children: report from an international working group. Blood. 2009 Mar 12;113(11):2386-93. doi: 10.1182/blood-2008-07-162503. 2009 55 21.0 Article 3 Olsson B.et al. T-cell-mediated cytotoxicity toward platelets in chronic idiopathic thrombocytopenic purpura. Nat Med. 2003 Sep;9(9):1123-4. doi: 10.1038/nm921. 2003 36 58.7 Article 4 xue. et al. Fever with thrombocytopenia associated with a novel bunyavirus in China. N Engl J Med. 2011 Apr 21;364(16):1523-32. doi: 10.1056/NEJMoa1010095. 2011 36 96.2 Article 5 Samuelsson A. et al. Anti-inflammatory activity of IVIG mediated through the inhibitory Fc receptor. Science. 2001 Jan 19;291(5503):484-6. doi: 10.1126/science.291.5503.484. 2001 34 44.7 Article 6 Provan D. et al. International consensus report on the investigation and management of primary immune thrombocytopenia. Blood. 2010 Jan 14;115(2):168-86. doi: 10.1182/blood-2009-06-225565. 2010 33 21.0 Review 7 Cines DB. et al. Immune thrombocytopenic purpura. N Engl J Med. 2002 Mar 28;346(13):995-1008. doi: 10.1056/NEJMra010501. 2002 31 96.2 Article 8 Kuwana M. et al. Splenic macrophages maintain the anti-platelet autoimmune response via uptake of opsonized platelets in patients with immune thrombocytopenic purpura. J Thromb Haemost. 2009 Feb;7(2):322-9. doi: 10.1111/j.1538-7836.2008.03161.x. 2009 29 5.5 Article 9 Liu XG. et al. High-dose dexamethasone shifts the balance of stimulatory and inhibitory Fcgamma receptors on monocytes in patients with primary immune thrombocytopenia. Blood. 2011 Feb 10;117(6):2061-9. doi: 10.1182/blood-2010-07-295477. 2011 28 21.0 Article 10 Neunert C. et al. The American Society of Hematology 2011 evidence-based practice guideline for immune thrombocytopenia. Blood. 2011 Apr 21;117(16):4190-207. doi: 10.1182/blood-2010-08-302984. 2011 28 21.0 Review Supplementary Material File (image2.tif) Download 1.47 MB File (image3.tif) Download 2.14 MB Information & Authors Information Version history V1 Version 1 25 February 2025 Copyright This work is licensed under a Non Exclusive No Reuse License. Keywords hematology immune thrombocytopenia immunology medical Authors Affiliations Xiaoyuan Fan [email protected] Xinjiang Medical University Affiliated First Hospital View all articles by this author Mingwei Li Xinjiang Medical University Affiliated First Hospital View all articles by this author Yunfei Zhang Xinjiang Medical University Affiliated First Hospital View all articles by this author Hongjie Jiao Xinjiang Medical University Affiliated First Hospital View all articles by this author Yingbin Yue Xinjiang Medical University Affiliated First Hospital View all articles by this author Mei Yan Xinjiang Medical University Affiliated First Hospital View all articles by this author Metrics & Citations Metrics Article Usage 255 views 174 downloads .FvxKWukQNSOunydq8rnd { width: 100px; } Citations Download citation Xiaoyuan Fan, Mingwei Li, Yunfei Zhang, et al. A bibliometric and visual analysis of immune thrombocytopenia-associated macrophages. Authorea . 25 February 2025. 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