Journal article
Platelet defects in patients and mice with Ehlers-Danlos syndrome
Blood, Vol.147(9), pp.987-997
02/26/2026
DOI: 10.1182/blood.2025029912
PMCID: PMC12982987
PMID: 41284637
Abstract
Ehlers-Danlos syndrome (EDS) is a group of connective tissue disorders characterized by joint hypermobility, skin hyperelasticity, perivascular tissue fragility, easy bruising, and increased bleeding risk. Abnormal bleeding in EDS ranges from mild ecchymoses to life-threatening hemorrhage. Platelet function abnormalities have been reported in people with EDS, but the broad nature and extent of these defects remain poorly defined. Herein, we evaluated blood samples from people with the hypermobile, classical, classical-like, and vascular types of EDS and utilized a Col5a1+/- mouse model of classical EDS to characterize the extent of platelet dysfunction. Our findings suggest that platelet dysfunction in EDS is an outcome of reduced integrin αIIbβ3 activation resulting from decreased phosphorylation of talin-1, leading to defects in aggregation and spreading. The observed platelet dysfunction was associated with reduced expression of the platelet surface receptors GPVI and PAR1 and impaired downstream signaling. Col5a1+/- mice demonstrated increased tail bleeding time, reproduced the signaling defects observed in platelets from people with EDS, and exhibited decreased susceptibility to FeCl3-induced carotid artery thrombosis. Collectively, our data indicate that platelet dysfunction in EDS is likely contributing to hemorrhagic complications.
Details
- Title: Subtitle
- Platelet defects in patients and mice with Ehlers-Danlos syndrome
- Creators
- Mariia Kumskova - University of IowaGagan D Flora - University of IowaManasa K Nayak - University of IowaIvan Budnik - University of IowaAditi Jain - University of IowaRakesh B Patel - University of Iowa, Iowa city, Iowa, United StatesAbhishek B Jha - University of IowaMadankumar Ghatge - University of IowaNeelam Chauhan - University of IowaJames V Michael - Thomas Jefferson UniversitySteven E McKenzie - Thomas Jefferson UniversityAnjali Sharathkumar - University of IowaJanice M Staber - University of Iowa Stead Family Children's Hospital, Iowa City, Iowa, United StatesSteven R Lentz - University of IowaAnil Chauhan - University of Iowa, Iowa city, Iowa, United States
- Resource Type
- Journal article
- Publication Details
- Blood, Vol.147(9), pp.987-997
- DOI
- 10.1182/blood.2025029912
- PMID
- 41284637
- PMCID
- PMC12982987
- NLM abbreviation
- Blood
- ISSN
- 0006-4971
- eISSN
- 1528-0020
- Publisher
- ELSEVIER
- Grant note
- Innovative Investigator Research Award (National Bleeding Disorders Foundation)American Society of Hematology Scholar AwardMentored Research Award (Hemostasis & Thrombosis Research Society)National Heart Lung and Blood Institute, National Institutes of Health: R01HL174419
The authors thank all the participants and their families for contributing their time and blood samples to this study. They thank Louis J. Soslowsky from the University of Pennsylvania for kindly sharing the Col5a1+/- mice. They are grateful to Jon Rodis for his continued support of this study. This work is supported by the Innovative Investigator Research Award (National Bleeding Disorders Foundation, formerly NHF) , the American Society of Hematology Scholar Award for Fellows, and the Mentored Research Award (Hemostasis & Thrombosis Research Society) (M.K.) , and the National Heart Lung and Blood Institute, National Institutes of Health grant R01HL174419 (A.K.C.) . The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health or other project sponsors.
- Language
- English
- Electronic publication date
- 11/24/2025
- Date published
- 02/26/2026
- Academic Unit
- Hematology, Oncology, and Blood & Marrow Transplantation; Stead Family Department of Pediatrics; Iowa Neuroscience Institute; Hematology/Oncology; Internal Medicine
- Record Identifier
- 9985035050002771
Metrics
29 Record Views