Global research trends and influential contributions in sickle cell disease: a bibliometric analysis of the top 100 cited papers

Abstract

Sickle cell disease (SCD) is one of the most common inherited hemoglobin disorders worldwide and remains a major cause of morbidity and mortality, particularly in low- and middle-income countries. Over the past several decades, SCD research has evolved from basic molecular investigations to clinical trials, epidemiological studies, and disease-modifying therapies. Highly cited publications represent the core scientific contributions that have shaped this field. This study aimed to analyze the top 100 most highly cited papers on SCD to identify influential publications, leading contributors, collaboration patterns, and major research hotspots. A bibliometric analysis was conducted using the Scopus database. English-language original articles and review papers published up to 31 December 2025 were retrieved using a predefined search strategy. Of 2,053 records identified, 2,031 relevant publications remained after screening and were ranked according to citation count. The top 100 most cited papers were selected for analysis. Bibliometric indicators including total citations (TC), citations per paper (CPP), relative citation index (RCI), and total link strength (TLS) were assessed. Network visualization and keyword co-occurrence analyses were performed using VOSviewer (version 1.6.20). The top 100 highly cited papers received between 347 and 7,694 citations, accumulating a total of 71,569 citations with a mean CPP of 715.69. Most publications (61%) were published between 1998 and 2023, while original research articles accounted for 83% of the dataset. The United States dominated highly cited SCD research, contributing 86 papers, 64,068 citations, and the highest TLS (71). Among institutions, the Medical College of Georgia and the University of Miami were leading contributors, while Elliott Vichinsky emerged as the most productive author. The New England Journal of Medicine published the largest number of highly cited papers (n = 29), whereas Science recorded the highest CPP (2270.8). Keyword co-occurrence analysis identified three major thematic clusters: (i) genetic and pathophysiological mechanisms, (ii) epidemiology and disease burden, and (iii) therapeutic interventions and clinical management. Highly cited SCD research is concentrated within a limited number of countries, institutions, authors, and high-impact journals, with the United States serving as the principal contributor. The intellectual structure of the field has evolved from fundamental molecular discoveries toward epidemiological research, clinical trials, and therapeutic innovations. These findings provide a comprehensive overview of the core literature in SCD and may help inform future research priorities, international collaborations, and evidence-based policy development.

Supplementary Information

The online version contains supplementary material available at 10.1007/s12687-026-00938-z.

Introduction

Sickle cell disease (SCD) is one of the most common inherited hemoglobin disorders worldwide and represents a major public-health challenge in many low- and middle-income countries. The disease results from a mutation in the β-globin gene leading to the production of hemoglobin S (HbS), which causes red blood cells to adopt a rigid, sickle shape under deoxygenated conditions (Kunz and Tagliaferri 2024). These abnormal erythrocytes lead to chronic hemolysis, vaso-occlusion, and a spectrum of complications including painful crises, stroke, organ damage, and premature mortality. Despite advances in clinical management, SCD continues to impose a substantial health burden globally, particularly in regions with limited access to comprehensive care and early diagnosis (Ware et al. 2017).

Globally, SCD is responsible for significant morbidity and mortality, particularly among children in sub-Saharan Africa, South Asia, and parts of the Middle East. Recent epidemiological estimates indicate that more than 300,000 infants are born annually with sickle cell anemia, and this number is projected to exceed 400,000 by 2050 if current demographic trends persist (Piel et al. 2013). Countries such as Nigeria, India, and the Democratic Republic of the Congo contribute disproportionately to the global burden of the disease due to high carrier frequencies and large population sizes (Piel et al. 2013). These epidemiological patterns highlight the need for robust scientific evidence to guide prevention strategies, screening programs, and therapeutic interventions.

Over the past several decades, scientific research on SCD has expanded substantially, encompassing diverse areas including molecular genetics, pathophysiology, epidemiology, clinical trials, and health-system interventions. Early research primarily focused on understanding the molecular basis of the disease, including the identification of hemoglobin S and its polymerization properties (Ingram 1957). Subsequent decades witnessed rapid progress in clinical research, particularly in the development of disease-modifying therapies such as hydroxyurea, chronic transfusion therapy, and hematopoietic stem cell transplantation (Serjeant 2013). These advances have significantly improved survival in high-income settings; however, the translation of scientific discoveries into population-level health benefits remains uneven across regions.

In addition to therapeutic advances, public-health interventions such as newborn screening programs, prophylactic antibiotics, vaccination strategies, and early disease management have demonstrated significant reductions in childhood mortality. For instance, randomized trials of penicillin prophylaxis in children with sickle cell anemia showed a substantial reduction in pneumococcal infections, establishing preventive therapy as a cornerstone of pediatric care (Gaston et al. 1986). Similarly, transcranial Doppler screening combined with chronic transfusion therapy has been shown to significantly reduce the risk of stroke among children with SCD (Robert J. Adams et al. 1998a, b). These landmark studies have shaped international clinical guidelines and remain among the most frequently cited contributions in the field.

Despite these advancements, the global research landscape of SCD remains uneven. A significant proportion of scientific output originates from high-income countries, particularly the United States and Europe, while regions bearing the highest disease burden contribute relatively fewer high-impact publications. This imbalance reflects disparities in research infrastructure, funding availability, and collaborative networks. Understanding how influential scientific contributions are distributed across countries, institutions, and journals is essential for identifying knowledge gaps and guiding future research priorities.

Bibliometric analysis has emerged as a valuable methodological approach for examining the structure and evolution of scientific literature. By analyzing citation patterns, authorship networks, and publication trends, bibliometric studies provide insights into the intellectual foundations and emerging directions of a research field (Tshilolo et al. 2019). Highly cited papers, in particular, represent influential contributions that shape scientific understanding, guide clinical practice, and stimulate further research. Evaluating the characteristics of such influential publications can help identify the key themes, leading institutions, and collaborative networks driving progress in a given discipline.

Several bibliometric studies have been conducted across medical specialties to identify the most influential publications and research trends. For example, analyses of highly cited papers in oncology, cardiology, and infectious diseases have revealed that seminal clinical trials, methodological innovations, and landmark epidemiological studies tend to dominate citation landscapes (Aljuaid et al. 2021). However, relatively few studies have comprehensively examined the citation dynamics and research hotspots in the field of sickle cell disease. Given the growing volume of literature and the multidisciplinary nature of SCD research, such analyses are increasingly necessary to map the intellectual structure of the field.

Furthermore, bibliometric mapping techniques such as co-authorship networks and keyword co-occurrence analyses allow researchers to visualize collaboration patterns and thematic clusters within the literature. These approaches help identify dominant research themes, emerging areas of investigation, and influential research groups. Tools such as VOSviewer have been widely used to analyze bibliographic data and generate network visualizations of scientific collaboration and knowledge structures (van Eck and Waltman 2010). Such analyses are particularly useful for understanding how scientific knowledge evolves and how collaborative networks contribute to the development of research fields.

In the context of SCD, identifying highly cited publications provides important insights into the evolution of scientific priorities over time. Early highly cited studies often focused on basic pathophysiology and genetic mechanisms, whereas more recent influential publications tend to emphasize clinical trials, disease management strategies, and global health perspectives. These shifts reflect the maturation of the field from fundamental biological research toward translational and public-health applications.

Sickle cell disease (SCD) represents an important and increasingly recognized public-health challenge in India, particularly among tribal and other vulnerable populations in several high-burden states. The large number of affected individuals, delayed diagnosis, recurrent complications, premature mortality, and substantial social and economic consequences make SCD research highly relevant to India’s health priorities (Colah et al. 2015). The launch of the National Sickle Cell Anaemia Elimination Mission, with the goal of eliminating SCD as a public-health problem by 2047, further emphasizes the need for robust Indian evidence to guide screening, genetic counselling, early diagnosis, treatment, and long-term follow-up. Research is particularly needed to understand regional variations in disease burden, genotype and phenotype, barriers to accessing care, treatment adherence, and the effectiveness of community- and primary-care-based interventions (Nair 2026). Strengthening SCD research in India is therefore essential not only for scientific advancement but also for reducing health inequities, improving access to comprehensive care, informing resource allocation, and accelerating progress toward the national elimination target (Colah et al. 2015).

Another important dimension of SCD research is the role of collaborative networks in generating high-impact scientific output. Multicenter studies and international collaborations have played a critical role in advancing knowledge about disease complications, treatment outcomes, and population-level burden. Large collaborative initiatives have enabled the conduct of randomized clinical trials and longitudinal cohort studies that would otherwise be difficult to implement in single institutions. Understanding the institutional and geographic patterns of collaboration in highly cited literature can therefore provide valuable insights into the drivers of scientific influence in SCD research.

From a public-health perspective, the analysis of highly cited SCD publications is particularly relevant for guiding research investment and policy priorities. Given the disproportionate burden of disease in resource-limited settings, there is a need to ensure that future research addresses health-system challenges, implementation barriers, and equity in access to care. Bibliometric analyses can help highlight areas where scientific attention has been concentrated and where further research efforts are needed.

Therefore, analyzing the top highly cited papers in SCD research can provide a comprehensive overview of the intellectual landscape of the field, identify key contributors and institutions, and reveal major thematic clusters that have shaped scientific progress. Such analyses not only help understand past research trends but also inform future directions for research and policy development.

Aim

The present study aimed to conduct a bibliometric analysis of the top 100 most highly cited papers on sickle cell disease to identify influential publications, research trends, collaborative networks, and major thematic areas in the field.

Objectives

1. To identify and analyze the top 100 most highly cited publications on sickle cell disease indexed in the Scopus database.

2. To examine the bibliometric characteristics of these publications, including citation counts, publication years, document types, and funding patterns.

3. To determine the most productive and influential countries, institutions, authors, and journals contributing to highly cited SCD research.

4. To explore collaborative networks among countries, institutions, and authors using bibliometric mapping techniques.

5. To identify major research hotspots and thematic clusters in highly cited SCD literature through keyword co-occurrence analysis.

Methods

Study design

This study employed a descriptive bibliometric design to analyze the top 100 most highly cited publications on sickle cell disease (SCD). Bibliometric methods were used to evaluate publication characteristics, citation impact, authorship patterns, institutional productivity, country contributions, collaborative networks, and research hotspots within the SCD literature.

Data source and search strategy

The Scopus database was selected as the data source because it is one of the largest multidisciplinary citation databases and provides comprehensive coverage of peer-reviewed scientific literature along with detailed citation information suitable for bibliometric analyses. A comprehensive search was conducted in the Scopus advanced search interface to identify publications related to sickle cell disease published up to 31 December 2025. The search strategy was developed through an iterative process and refined after pilot searches and verification of landmark publications in the field to ensure adequate sensitivity and specificity.

The following search query was used: TITLE (“sickle cell” OR “sickle cell disease”) AND PUBYEAR > 1921 AND PUBYEAR < 2026 AND (LIMIT-TO (DOCTYPE,“ar”) OR LIMIT-TO (DOCTYPE,“re”)) AND LIMIT-TO (PUBSTAGE,“final”) AND LIMIT-TO (SRCTYPE,“j”) AND LIMIT-TO (LANGUAGE,“English”). The search retrieved 2,053 records. Only original research articles and review articles published in English-language peer-reviewed journals were included. Letters, editorials, conference papers, notes, errata, and non-journal publications were excluded.

Selection of highly cited papers

Two independent investigators (SB and AS) screened the retrieved records to identify publications directly related to sickle cell disease. Any discrepancies were resolved through discussion and consensus. Following screening, 2,031 relevant publications remained for analysis. These publications were ranked in descending order according to their total citation count in Scopus. The top 100 most cited publications were subsequently selected and designated as Highly Cited Papers (HCPs) for detailed bibliometric analysis.

Data extraction

For each selected publication, the following bibliometric information was extracted from the Scopus database: publication year, journal title, document type, citation count, country of origin, institutional affiliation, authorship information, subject category, and funding details. Data were exported in Comma-Separated Values (CSV) format for further analysis.

Bibliometric indicators

The following bibliometric indicators were used to evaluate scientific productivity and impact:

• Total Citations (TC): Total number of citations received by a publication.

• Citations Per Paper (CPP): Average number of citations received per publication.

• Relative Citation Index (RCI): Ratio of the citations received by a publication or entity to the average citation rate of the study dataset.

• Total Link Strength (TLS): A VOSviewer-derived measure representing the overall strength of collaborative or bibliographic relationships among items within a network.

The most productive countries, institutions, authors, and journals were identified based on publication output, whereas the most influential entities were determined using CPP and RCI values(Vaishya et al. 2023).

Bibliometric mapping and network analysis

Bibliometric mapping was performed using VOSviewer software (version 1.6.20). Co-authorship analyses were conducted for countries, institutions, and authors to visualize collaborative relationships. Keyword co-occurrence analysis was performed to identify major research themes and hotspots within highly cited SCD literature.

VOSviewer employs the association-strength normalization method to generate network visualizations. In these maps, each node represents an item (author, institution, country, or keyword), node size reflects its weight or frequency, lines indicate relationships between items, and colors represent clusters generated by the software based on the strength of associations.

Keyword analysis

Author keywords and indexed keywords from the selected publications were extracted and analyzed. Keywords meeting the predefined occurrence threshold were included in the co-occurrence analysis. The VOSviewer clustering algorithm was used to group related keywords into thematic clusters, thereby identifying major research hotspots and intellectual structures within highly cited SCD research.

Data verification and quality control

To improve reliability, data screening and extraction were independently conducted by two investigators. Retrieved records were manually checked for relevance, duplicate entries, and indexing inconsistencies. Any disagreements were resolved through consensus. This process ensured the accuracy and consistency of the bibliometric dataset.

Methodological considerations

Citation-based analyses inherently favor older publications because they have had a longer period to accumulate citations. Consequently, recently published but potentially influential studies may be underrepresented. Furthermore, citation counts may be affected by factors such as journal visibility, self-citation practices, and differences in citation behavior across disciplines.

Reporting framework

The study was conducted and reported in accordance with established methodological recommendations for bibliometric research and science mapping studies, including the guidelines proposed by Donthu et al. and Aria & Cuccurullo for conducting and reporting bibliometric analyses (Aria and Cuccurullo 2017; Donthu et al. 2021).

Results

Highly cited papers (HCPs)

From the 2031 papers on Sickle cell Disease research, the top 100 received 347 to 7694 citations and were considered highly cited papers (HCPs) (Supplementary Table 1). Among these, 39% were published between 1949 and 1997, 61% were published between 1998 and 2023. Together, the first 100 HCPs registered 71,569 citations, averaging 715.69 citations per paper (CPP). These HCPs showed an uneven distribution of citations received: 61 fell in the citation range 347–548, 39 in 555–7694 (Supplementary Table 2). Among the document types, research articles (83.0%) constitute the largest output among the top 100 HCPs, followed by reviews (17.0%). 55% of the top 100 HCPs received extramural funding from more than 30 national and international foreign funding agencies. Most influential studies were supported by major governmental and philanthropic funding agencies, particularly the National Institutes of Health (NIH) and its National Heart, Lung, and Blood Institute (NHLBI), which have played a central role in supporting longitudinal cohorts, multicentre clinical trials, and translational research. Other important contributors include the Wellcome Trust, the Medical Research Council (United Kingdom), the European Commission, the Bill & Melinda Gates Foundation, and the National Institute for Health Research (NIHR) (R. J. Adams et al. 1998a, b; Piel et al. 2010).

Most productive and impactful countries

Thirty-nine countries were involved in the 100 HCPs, with 10 contributing 2–86 papers and Only one country, the United States, contributed more than the group average productivity (14.1 papers) Fig. 1. Only five countries (Germany, Canada, Greece, United States, Italy) registered CPP and a relative citation index (RCI) higher than the group average (686.46 and 0.96). The total link strength (TLS) of the top 10 countries varied from 11 to 71, with the highest links registered by USA (71), followed by the UK (54), and Canada (43). Supplementary Table 3 presents the bibliometric profile of the top 10 most productive and 10 most impactful countries in SCA research. The collaborative network linkage map of the top 10 countries with a minimum of 2 papers and 1725 citations each, using VOS viewer tool is shown in Fig. 2.

Fig. 1.

Output of the top 10 most productive Countries

Fig. 2.

Co-authorship Network Map of 10 Countries. (Each node in the map represents an Country, and the size of the node corresponds to the Countries productivity (i.e., the number of publications). The lines connecting the nodes illustrate the collaboration between the Countries, with the thickness of the links indicating the level of collaboration between them)

(Each node in the map represents an Country, and the size of the node corresponds to the Countries productivity (i.e., the number of publications). The lines connecting the nodes illustrate the collaboration between the Countries, with the thickness of the links indicating the level of collaboration between them).

Most productive and impactful organizations

In all, 286 organizations participated in the top 100 HCPs. The top 26 organizations contributed 5 to 7 papers and these together contributed 57 papers which received 47,803 citations, accounting for more than 57.0% and 66.7% share in 100 HCPs and citations. On further analysis, it was observed that 6 organizations were the most active and productive, as they contributed more than the average publication productivity (5.9) of all 10 organizations: The 7 organizations were more influential as they registered CPP and Relative Citation Index (RCI) of more than their group average (130.2 and 1.2) of top 10 organizations. Supplementary Table 4 presents the bibliometric profile of the top 10 most productive and 10 most impactful organizations. The TLS of the top 10 participating organizations varied from 17 to 78, with the Highest (78 TLS) depicted by Emory university, United States, followed by university of Miami, United States (n = 74), and medical university of south Carolina, United States (n = 72). Figure 3 presents a co-authorship map of the top 10 organisation, each with at least 5 publications. Among these 10 organisation, connections exist between them, and they have been divided into 4 clusters with 23 links and a TLS of 36 providing insights into their contributions to the field of top 100 HCPs in SCD.

Fig. 3.

Co- Authorship map between countries. (Each node in the map represents an Organisation, and the size of the node corresponds to the organisations productivity (i.e., the number of publications). The lines connecting the nodes illustrate the collaboration between the organisations, with the thickness of the links indicating the level of collaboration between them)

Most productive and impactful authors

In total, 573 authors contributed to the top 100 HCPs. The top 10 authors contributed 4 to 12 papers and these together contributed 59 papers which received 46,368 citations, accounting for 59.0% and 64.7% share in top 100 HCPs and citations. On further analysis, it was observed that 3 authors among the top 10 were the most active and productive as they contributed more than the average group productivity (5.9) of all 10 authors. They were Vichinsky, Elliott (n = 12), Steinberg, Martin H. (n = 8 ), and Gladwin, Mark T. (n = 7 each). The three authors Platt, Orah S., Castro, Oswaldo and Steinberg, Martin H. were more influential as they registered CPP and Relative Citation Index (RCI) of more than their group average (803.14 and 1.12) of top 10 authors. (Supplementary Table 5) presents the profile of the 10 most productive authors. Figure 4 presents a co-authorship map of the top 10 authors, each with at least 4 publications. Among these 10 authors, connections exist between some of them, and they have been divided into 3 clusters with 24 links and a TLS of 32. The co-citation analysis presents nine clusters of authors and their respective link strengths, providing insights into their contributions to the field of top 100 HCPs in SCD.

Fig. 4.

Co-authorship Network Map of 10 Authors. (Each node in the map represents an author, and the size of the node corresponds to the author’s productivity (i.e., the number of publications). The lines connecting the nodes illustrate the collaboration between the authors, with the thickness of the links indicating the level of collaboration between them)

Most productive and impactful journals

The 100 HCPs were published in 31 journals. The New England Journal of Medicine was among the top 31 contributing journals and had the most publications (n = 29), followed by Blood (n = 24), Proceedings of the National Academy of Sciences of the United States of America (n = 6), Science (n = 5), JAMA (n = 3), Journal of Clinical Investigation (n = 3), and The Lancet (n = 3). However, the most cited journal was Science (2270.8 CPP), followed by JAMA: Journal of the American Medical Association (1299.0 CPP), Nature Medicine (1122.0 CPP), PLOS Medicine (838.0 CPP), and the New England Journal of Medicine (825.7 CPP). Supplementary Table 6 lists the top ten journals by publication productivity, citations, and CPP .

Research hotspots

The keyword co-occurrence analysis of top 100 cited articles on Sickle cell Disease publications extracted 1288 Keywords; applying a 7-occurrence threshold in VOSviewer (v1.6.20) yielded 84 terms grouped into three thematic clusters (Fig. 5). The keyword co-occurrence analysis identified three major research clusters, revealing the principal research hotspots in sickle cell disease (SCD) research. Cluster 1 (Red Coloured) reflects a major hotspot related to the genetic and pathophysiological mechanisms of SCD. Frequently occurring keywords such as sickle cell anemia, hemoglobin S, globins, genotype, phenotype, fetal hemoglobin, and hemolysis highlight research focusing on the molecular basis of the disease, hemoglobin abnormalities, and genetic determinants influencing disease severity and clinical manifestations. The presence of terms such as hematopoietic stem cells and busulfan further indicates interest in cell-based therapeutic strategies and curative interventions. Cluster 2 (green-colored) reflects a hotspot centered on the epidemiology and population-level burden of SCD. Keywords including incidence, prevalence, mortality, survival rate, and risk factors emphasize studies investigating the distribution, determinants, and long-term outcomes of the disease across populations. Demographic terms such as infant, child, adolescent, and adult indicate research exploring age-specific patterns of disease occurrence, while terms like cerebrovascular accident highlight investigations into major complications contributing to morbidity and mortality. Cluster 3 (Blue Coloured) represents a hotspot related to therapeutic interventions and clinical management of SCD. Keywords such as hydroxyurea, antisickling agents, drug efficacy, and treatment outcome indicate extensive research on pharmacological and clinical strategies aimed at improving patient outcomes. The presence of methodological terms including randomized controlled trial, double-blind procedure, and multicenter study reflects the strong emphasis on evidence-based clinical trials evaluating treatment effectiveness and safety. Overall, the keyword clustering reveals that the major research hotspots in highly cited SCD literature revolve around molecular mechanisms of the disease, epidemiological patterns and clinical burden, and therapeutic strategies for disease management.

Fig. 5.

Co-occurrence network showing major thematic clusters in Sickle cell Disease research. Node size represents term frequency, and colors denote cluster membership. Map generated using VOSviewer (v1.6.20)

Discussion

The present bibliometric analysis provides a comprehensive overview of the intellectual landscape of highly cited sickle cell disease research. By examining the top 100 most cited publications, the study highlights the evolution of scientific priorities, the dominance of certain geographic regions and institutions, and the thematic structure of influential research within the field. These findings offer valuable insights into how scientific knowledge in SCD has developed over time and the factors that shape citation impact.

One of the most striking observations from the analysis is the temporal distribution of highly cited publications. Approximately 61% of the top 100 papers were published between 1998 and 2023, indicating a marked increase in influential research during the past two decades. This trend likely reflects advances in molecular biology, genomics, and clinical trial methodologies that have accelerated scientific discovery in hematology. Similar temporal patterns have been observed in other biomedical bibliometric studies, where rapid technological and methodological innovations drive increases in high-impact publications (Oh et al. 2017).

The uneven distribution of citations among the top papers also reflects the presence of seminal landmark studies that have shaped the field. Although citation count is widely accepted as an indicator of scientific influence, it does not necessarily reflect the true clinical or public health impact of a publication. Several landmark studies in sickle cell disease have fundamentally transformed patient care irrespective of their citation rankings. For example, the elucidation of the molecular basis of sickle cell disease by Ingram laid the foundation for modern molecular medicine (Frenette and Atweh 2007). Similarly, universal newborn screening, penicillin prophylaxis, transcranial Doppler screening for stroke prevention, and hydroxyurea therapy have dramatically improved survival and quality of life among individuals with sickle cell disease (Steinberg et al. 1997). These studies have reshaped clinical practice and international guidelines, illustrating that citation metrics should be interpreted alongside their real-world influence on patient outcomes and healthcare policy.

Several highly cited SCD publications correspond to major clinical trials or pivotal discoveries that significantly altered clinical practice. For example, randomized trials evaluating hydroxyurea therapy demonstrated reductions in painful crises and improved clinical outcomes among patients with SCD, leading to widespread adoption of the drug as standard therapy (Charache et al. 1995). Such landmark trials often generate exceptionally high citation counts because they influence treatment guidelines, stimulate subsequent research, and become foundational references in the field.

Another important finding is the overwhelming dominance of the United States in highly cited SCD research. In this analysis, the United States contributed 86 of the top 100 papers and accounted for the majority of total citations. This pattern mirrors findings from previous bibliometric analyses in hematology and other medical fields, where the United States consistently emerges as the leading contributor to highly cited research.

The predominance of highly cited publications from the United States appears to reflect decades of sustained investment in large collaborative research programmes rather than isolated investigations. The Cooperative Study of Sickle Cell Disease (CSSCD), conducted from the late 1970s through the 1990s, established one of the largest prospective longitudinal cohorts and generated numerous influential publications describing the natural history, clinical complications, and predictors of disease severity (Steinberg et al. 1997). Subsequent multicentre initiatives, including the Multicenter Study of Hydroxyurea (MSH), the Stroke Prevention Trial in Sickle Cell Anemia (STOP), the BABY HUG trial, the Silent Cerebral Infarct Trial (SIT), and more recent gene therapy studies, further advanced evidence-based management of sickle cell disease (Lee et al. 2006).

The concentration of highly cited publications within the United States is also likely influenced by regional differences in disease burden, specialized clinical centres, and research infrastructure. States such as Georgia, Tennessee, South Carolina, Maryland, and Pennsylvania have historically managed large populations of individuals with sickle cell disease and host internationally recognized research institutions, including the Medical College of Georgia, Emory University, Duke University, Johns Hopkins University, and the University of Miami (R. J. Adams et al. 1998a, b). These institutions have contributed substantially to landmark clinical trials, longitudinal cohort studies, and translational research. Although the present bibliometric analysis examined country-level contributions rather than state-level distributions, future investigations exploring regional research productivity within the United States could provide valuable insights into how demographic patterns, healthcare infrastructure, and institutional investment influence scientific leadership in sickle cell disease research.

Likewise, important contributions from Africa have largely emerged through structured collaborative programmes such as the KEMRI–Wellcome Trust Research Programme in Kilifi, Kenya, the MalariaGEN Consortium, and the H3Africa initiative (Ramsay and Sankoh 2016). These sustained research platforms demonstrate the importance of long-term investment, multidisciplinary collaboration, and robust research infrastructure in producing high-impact scientific evidence.

However, the geographic distribution of highly cited research raises important public-health considerations. Although the highest burden of SCD occurs in Africa and parts of Asia, these regions contributed relatively few highly cited publications. This imbalance highlights disparities in global research capacity and funding allocation.

The funding landscape of highly cited sickle cell disease research further illustrates the importance of sustained financial investment in scientific advancement. Most influential studies were supported by major governmental and philanthropic funding agencies, particularly the National Institutes of Health (NIH) and its National Heart, Lung, and Blood Institute (NHLBI), which have played a central role in supporting longitudinal cohorts, multicentre clinical trials, and translational research. Other important contributors include the Wellcome Trust, the Medical Research Council (United Kingdom), the European Commission, the Bill & Melinda Gates Foundation, and the National Institute for Health Research (NIHR). The strong representation of United States-based publications among the highly cited papers is therefore likely attributable, at least in part, to sustained funding mechanisms that have enabled large-scale collaborative research over several decades. Similar long-term investments may be required in high-burden regions to reduce existing disparities in research productivity. Studies have shown that research output in many low- and middle-income countries remains limited due to resource constraints, lack of infrastructure, and limited opportunities for international collaboration (Millward-Hopkins and Oswald 2023). Despite remarkable advances in the diagnosis and management of sickle cell disease, substantial global inequities persist. Approximately three-quarters of individuals living with sickle cell disease reside in sub-Saharan Africa, where access to newborn screening, comprehensive care, hydroxyurea therapy, blood transfusion services, and specialist healthcare remains limited (Ally and Balandya 2023). Consequently, childhood mortality remains unacceptably high in many low-income countries, whereas survival has improved dramatically in high-income settings through early diagnosis and comprehensive disease management (Obeagu 2025). This bibliometric analysis similarly demonstrates that relatively few highly cited publications originated from African countries despite the continent bearing the greatest disease burden. Strengthening research capacity, developing regional centres of excellence, expanding international collaborations, and ensuring sustainable funding are essential to align research output more closely with global disease burden. Lessons learned from successful collaborative programmes and funding models identified among the highly cited publications may provide a framework for reducing these persistent inequities.

The analysis also demonstrates that a relatively small number of institutions contribute disproportionately to highly cited SCD research. Institutions such as the Medical College of Georgia, Harvard Medical School, and the University of Miami emerged as leading contributors. These institutions have historically played central roles in SCD research, hosting specialized clinical programs and participating in large multicenter trials. Their strong collaborative networks likely contribute to higher citation impact and scientific visibility.

The concentration of influential research within a limited number of institutions reflects the broader phenomenon of “academic concentration,” where scientific influence tends to cluster within well-funded research centers. While such concentration can accelerate scientific progress, it may also limit diversity in research perspectives and reduce opportunities for emerging institutions in high-burden regions. Strengthening research capacity in low-resource settings should therefore be a key priority for global SCD research initiatives.

The analysis of authorship patterns further highlights the role of influential researchers in shaping the field. Authors such as Elliott Vichinsky, Martin Steinberg, and Mark Gladwin emerged as highly productive contributors to influential literature. These researchers have been instrumental in advancing knowledge on SCD pathophysiology, clinical management, and therapeutic innovations. Their frequent appearance in co-authorship networks reflects the importance of collaborative research in producing high-impact publications.

Research leadership represents another important dimension of scientific productivity that extends beyond publication counts. Although the present study evaluated authorship based on publication records, corresponding authorship may better reflect intellectual leadership, mentorship, and responsibility for the overall research programme. Many first authors of highly cited publications were trainees or early-career investigators working under established research groups. Consequently, analyses based solely on first authorship may underestimate the contributions of senior investigators who provided scientific leadership and developed the collaborative research infrastructure responsible for these influential studies. Future bibliometric analyses incorporating corresponding authorship may therefore provide additional insights into leadership patterns, capacity building, and mentorship within sickle cell disease research.

Keyword co-occurrence analysis revealed three major thematic clusters in highly cited SCD research: molecular mechanisms, epidemiology and disease burden, and therapeutic interventions. This thematic distribution reflects the multidisciplinary nature of SCD research. Early studies focused primarily on understanding the molecular basis of hemoglobin abnormalities and genetic determinants of disease severity (Ingram 1957). Over time, research expanded to include clinical trials evaluating disease-modifying therapies and epidemiological studies examining disease burden across populations.

The prominence of therapeutic research within highly cited literature underscores the importance of translational research in SCD. Advances in pharmacologic therapies, particularly hydroxyurea, have transformed the management of the disease and significantly improved patient outcomes (Charache et al. 1995). More recently, gene therapy and gene-editing approaches have emerged as promising curative strategies, generating increasing scientific interest and citation impact.

From a public-health perspective, the cluster focusing on epidemiology and population burden is particularly significant. Understanding the distribution and determinants of SCD is essential for designing effective screening programs and preventive interventions. Studies on newborn screening, survival patterns, and disease complications have provided critical evidence supporting early diagnosis and comprehensive care programs (Lees et al. 2000).

However, the relative scarcity of implementation research within highly cited literature suggests that more attention is needed to address health-system challenges. While clinical trials demonstrate the efficacy of interventions, their translation into real-world practice often faces barriers related to healthcare infrastructure, affordability, and accessibility. Future research should therefore emphasize implementation science approaches to ensure that scientific advances translate into meaningful population-level health improvements.

Another noteworthy finding is the predominance of high-impact journals such as the New England Journal of Medicine, Blood, and Science in publishing influential SCD research. Publication in such journals enhances visibility and citation potential, contributing to the high impact of these studies. Previous bibliometric analyses have similarly shown that highly cited biomedical research tends to be concentrated in a relatively small number of prestigious journals (Seglen 1997).

Taken together, the findings suggest that highly influential sickle cell disease research is driven not only by scientific innovation but also by sustained research programmes, stable funding, multidisciplinary collaborations, and strong institutional leadership. Citation metrics should therefore be interpreted alongside the broader context of clinical impact, public health significance, and equity. Future efforts should prioritize strengthening research infrastructure in regions with the highest disease burden, particularly sub-Saharan Africa and South Asia, to ensure that scientific advances translate into improved health outcomes for the populations most affected by sickle cell disease.

Limitations of the study

This study has several limitations. First, the analysis was based only on the Scopus database, and relevant papers indexed in other databases such as Web of Science or Google Scholar may have been missed. Second, citation count was used as the main indicator of impact, which may not always reflect the true scientific or clinical importance of a study. Citation numbers can also be influenced by factors such as publication age, journal visibility, and self-citation. Third, only English-language articles were included, which may have excluded relevant studies published in other languages. Fourth, the study focused only on the top 100 most cited papers, and therefore recently published but potentially influential studies may not yet have accumulated enough citations to be included. Another limitation is that the analysis was based on first authorship. As many first authors were trainees or early-career researchers, this approach may underestimate the contributions of senior investigators who provided scientific leadership and established the collaborative research networks behind these influential studies.

Finally, bibliometric analyses primarily reflect patterns of scientific publication and citation behavior, rather than the direct public-health impact of the research.

Authors’ contributions

Dr. Alok Singh, Dr. Sudip Bhattacharya: Concepts, Design, Definition of intellectual content, investigation, manuscript writing, Analysis, Manuscript reviewDr. Akanksha Singh, Dr. Sanjay Kini B, Dr. Vivek Singh, Dr. Neeraj Dubey, Dr. Ujjwal, Dr. Vakeel Khan, Miss. Arti Sharma, Dr. Himanshu Sahu Dr. Palak Khargonkar, Dr. Apoorva Wasnik, Dr. Deepanshi Saxena, -Concepts, Design, Definition of intellectual content, investigation, manuscript writing, Analysis, Manuscript review.

Funding

Nil.

Data availability

No datasets were generated or analysed during the current study.

Declarations

Ethical approval

NA.

Competing interests

The authors declare no competing interests.

AI Use Declaration

The authors used ChatGPT solely to improve the grammar, language, readability. All authors have reviewed and verified the final manuscript and accept full responsibility and accountability for its content.