Athn Transcends Natural History Cohort Study of Bleeding Symptoms and Treatment Outcomes in Patients with Glanzmann Thrombasthenia

Background Glanzmann thrombasthenia (GT) is a rare, inherited, qualitative platelet disorder caused by a deficiency of one or both platelet surface proteins alpha IIb beta 3. This protein on the platelet functions as the fibrinogen receptor and is essential for hemostasis. Individuals with GT have lifelong bleeding episodes that can be frequent and severe often involving the muco-cutaneous membranes. GT is an autosomal recessive disorder with variations of the ITGA2B or ITGB3 genes. The prevalence of GT is estimated to be 1:1,000,000 in the general population. In populations with high consanguinity, the prevalence is higher. Reports of the impact of living with GT are lacking. Platelets have previously been the mainstay of treatment for severe bleeding and to manage surgical bleeding in people with GT. However, platelet transfusions carry a number of risks including allergic reactions (anaphylaxis, acute lung injury), pathogen transmission, and the formation of allo-antibodies. Primary bleeding prophylaxis is currently not available and all treatment for bleeding is reactive and on-demand. As potential new therapies emerge, clinicians require unbiased, long-term data on the safety and effectiveness of both current and new therapies. Therefore, we designed a registry of people with GT with the aims of assessing the bleeding rate and phenotype for people with this condition, as well as describing their lived experience. Rationale Due to the rare nature of GT, data within individual center registries are naturally limited. There is variation in the data held and method of collection. The aim of the study is to collect biospecimens, phenotypic characteristics, bleeding patterns, and treatment utilization, from people who have been diagnosed with GT. To achieve this, a comprehensive, multi-institutional, observational cohort study will be conducted to: Allow collection of longitudinal safety and clinical practice data for treatments in patients with GT, allowing monitoring of recently approved and well-established therapies; Aid new discovery, through the collection of biospecimens and phenotype data; Provide sufficient, unified data capture in participants with this rare disorder across the United States. Objectives To describe the bleeding phenotype in GT, including the frequency of bleeds, the Site of bleeds, and to describe real-world effectiveness of therapies used in GT, by evaluating; the frequency of bleeds, Patient reported outcomes, Healthcare and tre