Evaluating the Burden of Glanzmann Thrombasthenia: A Systematic Literature Review to Identify Research Priorities

Objectives

Glanzmann thrombasthenia (GT) is a rare inherited platelet disorder caused by quantitative or qualitative defects in integrins αIIb and β3 expressed on the platelet surface. Variants in ITGA2B and ITGB3 render GPIIb/IIIa receptor for fibrinogen absent or non-functional on platelets, hindering platelet aggregation. Consequently, the inability to form stable clots, leads to considerable variability in bleeding severity, from minimal bleeding to potentially life-threatening bleeds, that contribute to iron deficiency anemia (IDA) and deteriorating quality of life (QoL). The impacts of GT are acutely felt across both sexes, nevertheless females face additional challenges due to heavy menstrual bleeding and bleeding with pregnancy delivery, that can result in significant IDA, adverse maternal and fetal outcomes. Current standard of care for most patients is on-demand, with no approved therapies for primary prophylaxis; existing treatments like rFVIIa and platelet transfusions are limited by short half-lives and complications. As novel treatments are developed it is essential to understand and demonstrate the burden of GT in terms of socio-economic burden on healthcare systems, patients, and their families. This study aimed to identify priorities and guide future burden research in GT, by reviewing existing research on the burden, QoL and economic cost impact of GT.

Methods

A systematic literature review of databases (MEDLINE®, Cochrane Library) and conference proceedings (including ISPOR, ISTH, ASH, WFH, and EAHAD) from January 2000 to April 2024 was conducted. Two reviewers independently double-screened studies according to pre-defined criteria. Data extraction included objectives, study population, study design, and the study results relating to burden of disease and of IDA, healthcare, bleeding, psychosocial, relationships, QoL, patient reported outcomes, costs, productivity and activity. Research priorities were developed based upon literature and upon the key areas of evidence to support the socio-economic burden of rare diseases.

Findings

Of 237 titles and abstracts screened, 18 relevant published studies (22%) & conference abstracts (78%) were identified for review. Of the 18 studies, 7 (39%) were conducted in the US with Saudi Arabia (17%) the second most common location. The most common study designs were chart reviews (56%) and surveys (22%) with sample sizes ranging from 8 to 133. Research mainly focused on the burden of bleeding (89%) and healthcare (72%), with the burden of psychosocial & relationships (44%), and IDA (17%) also reported. Limited information was reported upon productivity & activity (39%), QoL (33%) and cost (6%).

Research Priorities

Although evidence has been collected on the bleeding and healthcare burden, limited evidence has been published on the cost of illness associated with GT. A notable gap remains in understanding the comprehensive cost of illness associated with GT, including direct costs to healthcare system and indirect costs, often measured via productivity losses, impacting individuals and families; both of which are critical for a complete economic evaluation. Future research should prioritize capturing these costs directly or by applying unit costs to existing outcome data to build a robust economic case. Moreover, GT also exerts a profound psychological and social toll. From the research identified, patients often face prolonged diagnostic journeys, and can be misdiagnosed for years whilst facing significant burden from frequent bleeds which are often managed outside of healthcare setting. Few studies collected patient reported outcomes and QOL data. Further research is needed in this area to understand how bleeding, IDA, management strategies, and misdiagnosis impact QoL. Finally, the burden on caregivers, who often reduce their working hours or terminate employment to provide care, needs to be explored in further detail to capture the full holistic impact of GT.

Conclusions

Overall, there is a paucity of evidence elucidating the burden, QoL and economic cost impact on people with GT and caregivers. People with GT face significant burden from frequent bleeds which are often unreported to their healthcare professionals. Additional research focused on patients and caregivers is needed to characterize the real-world burden of bleeding & IDA on QoL, direct healthcare costs, and indirect costs from productivity loss.

Morgan:Hemab Therapeutics: Research Funding. Bristow:Hemab Therapeutics: Research Funding.