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Thank you for attending THSNA 2026. The virtual meeting is now closed.
Presentation Details
| Clinical Diagnosis and Management Strategies in Persons with Bleeding Disorders of Unknown Cause: A Scoping Review Evangelina Clark1, Ling-Yi Guo1, Diane Lorenzetti2, 3, Rafal Asmaro4, Dawn Goodyear4, 5, Natalia Rydz4, 5, Julia Hews-Girard6, Roy Khalife7, 8, Kelsey Uminski4, 5. 1Department of Medicine, University of Calgary, Calgary, AB, Canada.2Health Sciences Library, University of Calgary, Calgary, AB, Canada.3Department of Community Health Sciences, Calgary, AB, Canada.4Division of Hematology and Hematologic Malignancies, Calgary, AB, Canada.5Southern Alberta Rare Blood and Bleeding Disorders Comprehensive Care Program, Calgary, AB, Canada.6Faculty of Nursing, University of Calgary, Calgary, AB, Canada.7Ottawa Hospital Research Institute, Ottawa, ON, Canada.8Division of Hematology, Department of Medicine, Ottawa, ON, Canada |
Abstract
Background: Bleeding Disorder of Unknown Cause (BDUC) is a diagnostic entity characterized by clinically significant bleeding (quantified with a bleeding score) without abnormalities on standard hemostasis investigations. In recent years, BDUC has increasingly been recognized as an independent diagnosis, leading to a greater number of referrals to specialized bleeding disorder clinics and treatment centres. Despite this recognition, guidelines and standardized methods for diagnosis and management are lacking, resulting in morbidity from bleeding complications. Objectives: To examine diagnostic and management approaches for patients with BDUC within the literature. Methods: A scoping review was conducted in accordance with JBI guidelines with a protocol published on the Open Science Framework (https://doi.org/10.17605/OSF.IO/BEMVU). A comprehensive search of MEDLINE, Embase, Scopus, Web of Science, and Cochrane databases was conducted from inception to May 2025. Studies were included if they focused on the diagnosis or management (acute bleeding, perioperative, peripartum) of persons with BDUC (or associated terminology). Three reviewers independently performed title and abstract screening, full text screening, and data extraction. Data were analyzed with descriptive statistics and thematic analysis. Results: A total of 6099 unique abstracts were screened and 50 studies met criteria for inclusion (35 papers, 15 conference abstracts). Heterogeneity in study design was noted, including narrative reviews (n=4), surveys/audits (n=4), cohort/case-control studies (n=40), one systematic review, and one guideline. Of these, 33 focused on BDUC diagnosis, 10 on BDUC management, and 7 on both. There was variability in diagnostic terminology. BDUC, introduced by the ISTH as preferred nomenclature in 2021, has since been used far more frequently than prior labels, most of which appeared only once and lacked recurrence prior to 2021. Among studies describing BDUC diagnosis, minimum laboratory investigations were embedded within the definition of BDUC in 27, most commonly including core hemostatic tests such as CBC, PT/aPTT, von Willebrand Factor activity/antigen, FVIII, FIX, fibrinogen, and platelet aggregometry. A total of 34 studies evaluated diagnostic utility of specialized or research-based assays – including global coagulation/fibrinolysis profiling and genetic methods, yet the majority demonstrated limited clinical utility for diagnosing BDUC. Among management-focused studies (n=17), 16 addressed surgical/periprocedural prophylaxis, 12 pregnancy/peripartum care, and 7 dental interventions. The most frequently cited hemostatic prophylactic therapies across procedures were tranexamic acid and desmopressin. Many studies recommended clinical observation without hemostatic prophylaxis yet offered no criteria or context for when this strategy should be used. Additionally, clinician rationale for selecting specific hemostatic prophylactic agent(s) was rarely described, underscoring a critical gap in understanding real-world, individualized hemostatic decision-making. Conclusions: This scoping review demonstrates variability in both diagnostic evaluation and periprocedural hemostatic management for individuals labeled BDUC. Standardizing foundational laboratory criteria is a priority; however, future diagnostic guidance must remain adaptable to local test availability to ensure pragmatic implementation. Variation in procedural bleeding management appears influenced by clinician decision-making, yet the literature provides minimal insight into the reasoning or frameworks guiding individualized hemostatic strategies. To advance toward relevant and context-sensitive diagnosis and management recommendations, subsequent research should focus on defining clinical decision-making drivers and developing practical, adaptable guidance for real-world care settings.
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No part of this publication may be reproduced, distributed, or transmitted in any form or by any means, including photocopying, recording, or other electronic or mechanical methods, without the prior written permission of the author.