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Introduction: Membranopathies encompass haemolytic disorders arising from genetic variants in erythrocyte membrane proteins, including hereditary spherocytosis and stomatocytosis. Congenital dyserythropoietic anaemia type II (CDA II) is associated with the SEC23B gene and can exhibit phenotypic similarities to membranopathies. Current treatment options for these conditions, apart from splenectomy, are primarily supportive. Mitapivat, a novel pyruvate kinase (PK) activator, has demonstrated efficacy in increasing haemoglobin levels and reducing haemolysis in patients with PK deficiency, thalassemia, sickle cell disease and a mouse model of hereditary spherocytosis., Methods and Analyses: Sa fe t y and eff i cacy of mitapivat s ul f ate in adult patients with er y throcyte membranopathies (SATISFY) is a prospective, multicentre, single-arm phase two trial involving approximately 25 adult patients (≥18 years) diagnosed with a membranopathy or CDA II. During the 8-week dose escalation period, subjects will receive an initial dose of 50 mg mitapivat two times per day and may increase to 100 mg two times per day at week 4 based on the safety and changes in haemoglobin levels. Patients tolerating mitapivat well may be eligible to continue in two consecutive 24-week fixed dose periods.The primary objective of this study is to evaluate the safety of mitapivat, assessed through the occurrence of treatment-emergent adverse events. Secondary objectives include assessing the effects of mitapivat on haemoglobin levels, haemolysis, erythropoiesis, patient-reported outcome measures and spleen size.SATISFY aims to assess the safety and efficacy of mitapivat in adult patients with red blood cell membranopathies and CDA II, with the aim of establishing proof-of-concept in patients living with these rare conditions., Ethics and Dissemination: NCT05935202/CTIS:2023-503271-24-01. Findings will be published in peer-reviewed journals., Trial Registration Number: Clinicaltrials.gov, NCT05935202. CTIS:2023-503271-24-01. Registered 07-July-2023. Protocol number: 2.1. https://clinicaltrials.gov/study/NCT05935202., Competing Interests: Competing interests: AG: consultant for Agios Pharmaceuticals, Bristol Myers Squibb, Novartis Pharmaceuticals, Novo Nordisk A/S, Pharmacosmos UK Ltd and Vertex Pharmaceuticals; received research support from Agios Pharmaceuticals, Novo Nordisk A/S, Saniona and Sanofi. EJvB: advisory committee member for Agios Pharmaceuticals.; received research funding from Agios Pharmaceuticals, Novartis Pharmaceuticals, Pfizer and RR Mechatronics International B.V. KHMK: consultant for Agios Pharmaceuticals, Alexion Pharmaceuticals, Inc., Bristol Myers Squibb, Forma Therapeutics, Pfizer, Novo Nordisk A/S and Vertex Pharmaceuticals; received honoraria from Bristol Myers Squibb and Novo Nordisk A/S; member of the data safety monitoring board of Bioverativ; received research funding from Agios Pharmaceuticals and Pfizer. RvW: consultant for Agios Pharmaceuticals; research funding from Agios Pharmaceuticals and Pfizer. MAER: research funding from Agios Pharmaceuticals and Axcella Health., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Congenital platelet disorders (CPDs) are rare bleeding disorders that are associated with mucocutaneous bleeds. However, data on vaginal bleeding in women with CPDs are scarce. A set of generic and bleeding-specific questionnaires were used to evaluate the prevalence of vaginal bleeding, its impact on quality of life (QoL) and sexual functioning and the consequences for pregnancy, miscarriage and delivery in a cohort of women who were referred for diagnostic evaluation for CPDs. A total of 78 women included in the study were either diagnosed with a CPD (n = 35) or were clinically suspected of a CPD (n = 43). Heavy menstrual bleeding (HMB) was reported by a large proportion of women, which mainly started at menarche. In all, 76% of women received any kind of HMB treatment, often leading to surgical prodecures. HMB was shown to have a high impact on QoL, which improved upon treatment. Even though women reported that vaginal bleeding affects sexuality, this topic is not frequently discussed with physicians. Heavy blood loss frequently occurred after miscarriage/delivery, often requiring treatment. Women with (suspected) CPDs frequently encounter HMB, negatively impacting daily life and sexual functioning. Together with peripartum bleeding, these data highlight the burden of vaginal bleeding in CPDs and importance of adequate treatment., (© 2021 The Authors. British Journal of Haematology published by British Society for Haematology and John Wiley & Sons Ltd.)