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Thank you for attending THSNA 2026. The virtual meeting is now closed.
Presentation Details
| Novel Fibrinolysis Assays show alterations in clot lysis in Adolescents with Heavy Menstrual Bleeding and Bleeding Disorder of Unknown Cause Ruchika Sharma1, Laura Ketelboeter2, Chad Skaer2, Manoj Paul2, Lindsey Hartland1, Kendra Malone1, Chao Xing3, Song Xhang3, Michael Wu4, Christian Kastrup2, Ayesha Zia1. 1Division of Hematology/Oncology/BMT, Department of Pediatrics, University of Texas Southwestern Medical Center, Children's Health Dallas, Dallas, TX, USA.2Versiti Blood Research Institite, MIlwaukee, WI, USA.3O'Donnell School of Public Health, UT Southwestern Medical Center, Dallas, TX, USA.4Division of General Internal Medicine, Department of Internal Medicine, UT Southwestern Medical Center, Dallas, TX, USA |
Abstract
Background: Up to 60% patients referred to hematology experts for clinically significant bleeding are diagnosed as “bleeding disorder of unknown cause” (BDUC), an emerging entity in clinical practice. Our group and others have previously shown that in adolescents with heavy menstrual bleeding (HMB), ~ 33% are diagnosed with an underlying bleeding disorder in tertiary care settings. This leaves approximately 60% females with an undiagnosed bleeding disorder. These patients receive non-targeted interventions and may have sub-optimal treatments. Understanding mechanisms of unexplained bleeding in these patients is critical to advancing the care of this underserved population. Objectives: Our objective was to describe defects of fibrinolysis in adolescents with HMB and BDUC through investigational assays of fibrinolysis and proteomic studies. Methods: Adolescents with HMB and BDUC were recruited from January 2024- December 2024 from coagulation clinics and young women’s clinics at UT Southwestern Medical Center and Children’s Health, Dallas, TX. Validated tools including the International Society of Thrombosis and Haemostasis bleeding assessment tool (ISTH BAT) and the pictoral blood assessment chart (PBAC) were used to measure severity of bleeding symptoms and menstrual blood loss. Recent ISTH BAT case definition was used to define BDUC. HMB was defined as PBAC score >100. Plasma concentrations of fibrinolytic proteins were evaluated for plasminogen, thrombin activatable fibrinolysis inhibitor (TAFI) and antiplasmin using ELISA kits following the manufacturer’s guidelines. Rotational thromboelastometry (ROTEM) (Rotem Delta, Werfen S.A., Spain) was performed according to the manufacturer’s instructions. Plasminogen activation in plasma-derived clots was assessed using a high-throughput fluorescent assay based on previously described protocol with specific modifications. A generalized linear regression model was used to assess the relationship between patient assay values that met the 120 minute endpoint run time compared to a standard control assay. Results: 26 adolescents with HMB and ISTH BAT score >3 were recruited. Mean age was 14.6 years (12-17 years). Mean PBAC score was 659.4 (100-2910) and mean ISTH BAT score was 4.56 (3-13). Mean hemoglobin was 8.9 g/dl (range 5.1-13.7 g/dl) and mean ferritin was 6.4 ng/ml (0.5-11.6). 40% of the patients received blood transfusion and 76% received intravenous iron therapy. (table 1) Plasma concentrations of fibrinolytic proteins showed that TAFI was not altered compared to control. However, antiplasmin concentrations were significantly reduced and plasminogen concentrations were significantly elevated compared to pooled normal control plasma. ROTEM studies showed clot formation and lysis parameters including %LI30 was not significantly altered compared to control. Plasminogen activation assay showed significantly elevated plasminogen activation in the plasma of cases compared to control samples (P <0.0001) (figure 1). Conclusions: Systemic fibrinolysis is increased in females with HMB and BDUC. This lays the foundation for future studies evaluation treatment algorithms in HMB. Additionally, these studies provide a cohort for study of mechanistic insights into BDUC for future research. Acknowledgements: The authors received funding from cascade hemophilia consortium for completion of these studies.
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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.