Gender Disparity in Platelet Adhesion and Aggregation Disorders: A Quarter Century Analysis of Bernard Soulier Syndrome and Glanzmann Thrombasthenia Clinical Trials
Authors: Escobar Gil Tomas , Borja Montes Oscar , Ebaid Ala , Quintana Dulcinea 
Published: December 2024

Introduction: Platelet adhesion and aggregation disorders, such as Bernard Soulier Syndrome (BS) and Glanzmann Thrombasthenia (GT), are rare but clinically significant conditions characterized by impaired platelet function (1). BS, also known as hemorrhagiparous thrombocytic dystrophy, results from deficiencies in glycoprotein Ib-IX-V complex, while GT, or Thrombasthenia of Glanzmann and Naegeli, stems from abnormalities in glycoprotein IIb/IIIa (2). Despite their rarity, these disorders pose challenges in clinical management due to their potential for severe bleeding complications (1,2). Research efforts have focused on studying their pathophysiology, improving diagnostic strategies, and exploring therapeutic interventions. This descriptive, retrospective study aims to analyze randomized controlled trials (RCTs) conducted over a 25-year period to provide insights into participant demographics, geographical distribution of trials, and temporal trends in publication.

Methods: In this descriptive, retrospective study, we conducted a comprehensive search across multiple databases including PUBMED, ClinicalTrials.gov, Cochrane Central, and EMBASE, from January 1999 to July 2024. We identified publications reporting RCTs focused on platelet adhesion and aggregation disorders, specifically BS, and GT and data were extracted on the number of participants, their gender distribution, the countries where trials were conducted, and the year of publication. Descriptive statistical analyses were performed to summarize these variables and explore trends over time.

Results: We identified 15 studies encompassing a total of 14636 individuals with BS, and GT, among other platelet disorders. Among these trials, 47% of participants were male and 53% were female. Notably, Iran and Italy are the most prominent researchers in the topic. Of the RCT proportion, Iran led with approximately 19.05% of the research studies. Italy followed at 14.29%; and France, Germany, Canada, and the USA each contributed about 9.52%. Hungary, Turkey, Israel, and Thailand each accounted for approximately 4.76%. Analysis of publication trends revealed that 66% of the RCTs were conducted in the past decade. The male-to-female ratio varied across different time periods but was mostly female predominant: it was 0.4 for RCTs performed between 1999 and 2002, 0.66 for RCTs between 2012 and 2017, and 4.25 for RCTs conducted between 2019 and 2024 (just one study), reflecting evolving gender distributions in VWD research over time but mainly female-centered. Notably, 8 of the 15 studies did not report the gender of participants.

Conclusions: The findings of this study highlight the research efforts focused on Bernard Soulier Syndrome and Glanzmann Thrombasthenia over the past 25 years. Iran and Italy emerge as leaders in conducting RCTs within this field. The predominance of female participants in most of the studies suggests a shift in research focus towards understanding gender-specific aspects of these disorders. Equal gender inclusion should be considered when designing future trails. Interestingly, several of the studies did not report the gender in their results, which makes the gender parity analysis harder and less accurate. Additionally, to our knowledge, there have been no randomized clinical trials of these platelet disorders in Hispanics or RCTs done in Latin America, which uncovers gaps in understanding of these disorders across diverse racial and cultural contexts. Addressing these gaps through more international RCTs is crucial for gaining comprehensive insights into the complexities of these hematologic conditions within different populations.