Abstract
HTRS2025.O8A.2 Abstract Travel Award Unraveling Platelet Dysfunction in Ehlers-Danlos Syndrome: Linking Megakaryocyte Abnormalities to Hemorrhagic Risk
Research and practice in thrombosis and haemostasis, Vol.9, 103142
11/2025
DOI: 10.1016/j.rpth.2025.103142
Abstract
Background: Individuals with Ehlers–Danlos syndrome (EDS) face a heightened risk of hemorrhage, ranging from mild bruising to life-threatening bleeding. While previous studies have indicated platelet dysfunction in EDS, the specific mechanisms involved remain unclear.
Objectives: This study aims to characterize platelet function in EDS.
Methods: We collected blood samples from 43 participants with various EDS types—hypermobile (39%), classical (33%), classical-like (23%), and vascular (5%)—and compared them to 43 age- and gender-matched healthy controls. Additionally, we used COL5A1+/- mice as a murine model for the classical type of EDS. Platelet function was assessed through agonist-induced in vitro assays (including platelet aggregation, αIIbβ3 activation, P-selectin exposure, dense granules secretion, and spreading on fibrinogen) while plasma inflammatory markers and soluble GPVI (sGPVI) levels were measured using ELISA, and platelet signaling by Western blot assay. Megakaryocytes were isolated from the bone marrow via magnetic beads isolation and analyzed by flow cytometry assay.
Results: The mean age of the whole study population was 39.2 (range 16-69); 97% were female, and 7% were male. Platelets from EDS participants displayed significantly reduced aggregation and αIIbβ3 activation in response to collagen, collagen-related peptides, and thrombin receptor activator peptide-6, despite normal surface expression of αIIbβ3 (p < 0.01). They also demonstrated impaired platelet spreading on fibrinogen-coated surfaces (p < 0.01). Platelet functional deficits were associated with decreased phosphorylation of LAT (Y212), PLCγ2 (Y1217), and talin-1 (S425) upon collagen stimulation (p < 0.05). Platelet granule secretion levels were similar across both groups. Plasma analysis revealed elevated TNFα levels in EDS participants (p < 0.01), with no correlation to platelet aggregation, and normal IL6 levels. COL5A1+/- mice exhibited a similar platelet function phenotype, with defects in aggregation, αIIbβ3 activation, LAT (Y212), PLCγ2 (Y1217) phosphorylation, and spreading compared to wild-type mice. Both human and mouse EDS platelets demonstrated decreased GPVI surface expression compared to control groups (p < 0.01). Human plasma sGPVI levels were comparable between groups. Analysis of the bone marrow-derived megakaryocytes from COL5A1+/- mice showed lower GPVI levels compared to wild-type mice (p < 0.05).
Conclusions: This study is the first to reveal that EDS platelets exhibit reduced baseline GPVI expression associated with defects in integrin αIIbβ3 signaling. Findings from the EDS mouse model suggest that platelet dysfunctions in EDS subjects may arise from megakaryocyte abnormalities. The similar levels of sGPVI, normal IL-6 levels, and lack of correlation between elevated TNFα and platelet function imply that the chronic inflammatory state in EDS may not contribute to platelet dysfunction.
Details
- Title: Subtitle
- HTRS2025.O8A.2 Abstract Travel Award Unraveling Platelet Dysfunction in Ehlers-Danlos Syndrome: Linking Megakaryocyte Abnormalities to Hemorrhagic Risk
- Creators
- Mariia Kumskova - University of IowaGagan D. Flora - University of IowaManasa K. Nayak - University of IowaRakesh B. Patel - Department of Internal Medicine, University of Iowa, Iowa City, USIvan Budnik - University of IowaMadankumar Ghatge - Department of Internal Medicine, University of Iowa, Iowa City, USNeelam Chauhan - University of IowaAbhishek B. Jha - University of IowaAditi Jain - University of Iowa, Internal MedicineJanice M. Staber - University of IowaSteven R. Lentz - University of IowaAnil K. Chauhan - University of Iowa
- Resource Type
- Abstract
- Publication Details
- Research and practice in thrombosis and haemostasis, Vol.9, 103142
- DOI
- 10.1016/j.rpth.2025.103142
- ISSN
- 2475-0379
- eISSN
- 2475-0379
- Publisher
- Elsevier Inc
- Language
- English
- Date published
- 11/2025
- Academic Unit
- Hematology, Oncology, and Blood & Marrow Transplantation; Stead Family Department of Pediatrics; Iowa Neuroscience Institute; Hematology/Oncology; Internal Medicine
- Record Identifier
- 9985090639702771
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