Characterization of Bleeding Disorders in EDS

Disordered Bleeding in Ehlers Danlos Syndromes

Ehlers-Danlos Syndrome (EDS) is a disease that weakens the connective tissues (i.e. tendons and ligaments) in the human body. EDS can make the joints loose and alter skin and wound healing. It can also weaken blood vessels and organs. Many EDS patients are referred for investigation of bleeding symptoms. Although most patients will have mild symptoms such as bruising, many will experience significant bleeding that can be life-threatening. The physiological reason behind this has not been identified and therefore, treating this is challenging. In addition, patients with EDS frequently require major surgery due to complications from their connective tissue disease. These surgery carries a significant risk of catastrophic bleeding which is further magnified in this group of patients. The specific reason of clinical bleeding in patients with EDS is likely multifactorial, including skin and blood vessel fragility leading to increased bruising and poor wound healing, coagulopathies related to factor deficiency, acquired vonWillebrand disease (VWD), and notable platelet dysfunction.

Despite compelling preliminary evidence, there is limited data on the diagnosis and management of platelet dysfunction in EDS patients. Therefore, in this study we will characterize hemostasis, the medical term which refers to the process of stopping blood flow, across the three most common subtypes of EDS.we will also determine the burden of illness of pathologic bleeding in patients with Ehlers-Danlos Syndrome (EDS) using validated patient reported tools.

Study Overview

• Status: Enrolling by invitation
• Conditions: Hypermobile Ehlers-Danlos Syndrome; Ehlers-Danlos Syndrome; Vascular Ehlers-Danlos Syndrome; Hypermobile EDS (hEDS); EDS; Classical Ehlers-Danlos Syndrome; Classical EDS (cEDS); Vascular EDS (vEDS)
• Intervention / Treatment: Other: 20 ml venous blood collection

• Study Type: Observational
• Enrollment (Anticipated): 45

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5G 2C4
      • GoodHope EDS - Toronto General Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: N/A

• Sampling Method: Non-Probability Sample

Study Population

Any adult (≥ 18 years) patient with a known diagnosis of Ehlers Danlos Syndrome (Subtypes Classical, Hypermobile, or Vascular) as per the 2017 International Classification of Ehlers Danlos Syndrome.

Description

Inclusion Criteria:

• Any adult (≥ 18 years) patient with a known diagnosis of Ehlers Danlos Syndrome (Subtypes Classical, Hypermobile, or Vascular) as per the 2017 International Classification of Ehlers Danlos Syndrome.

Exclusion Criteria:

• Subtypes of Ehlers Danlos Syndrome which are not Classical, Hypermobile, or Vascular.
• Unable or unwilling to consent for the study

Study Plan

How is the study designed?

Design Details

• Observational Models: Other
• Time Perspectives: Cross-Sectional

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Hypermobile EDS; Individuals with a confirmed diagnosis of hypermobile EDS	Other: 20 ml venous blood collection; participant blood sample will be divided between sample EDTA sample tubes for thrombin generation testing and viscoelastic (ROTEM) testing of impaired hemostasis
Classical EDS; Individuals with a confirmed diagnosis of classical EDS	Other: 20 ml venous blood collection; participant blood sample will be divided between sample EDTA sample tubes for thrombin generation testing and viscoelastic (ROTEM) testing of impaired hemostasis
Vascular EDS; Individuals with a confirmed diagnosis of vascular EDS	Other: 20 ml venous blood collection; participant blood sample will be divided between sample EDTA sample tubes for thrombin generation testing and viscoelastic (ROTEM) testing of impaired hemostasis

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
The prevalence of platelet dysfunction among patients with a known diagnosis of EDS	6 months

Secondary Outcome Measures

Outcome Measure	Time Frame
The severity of platelet dysfunction (as characterized by the percentage of non-functional platelets) in patients with EDS	6 months
The prevalence and severity of impaired thrombin generation as assessed through thrombin generation testing in patients with EDS	6 months
The prevalence and severity of impaired hemostasis as assessed through viscoelastic testing (ROTEM) in patients with EDS	6 months
The prevalence and severity of bleeding as assessed via the ISTH-BAT scale in patients with EDS	6 months

Collaborators and Investigators

• Sponsor: University Health Network, Toronto
• Investigators: Principal Investigator: Nimish Mittal, MBBS, MD, University Health Network - University of Toronto

Study record dates

Study Major Dates

• Study Start (Actual): November 1, 2022
• Primary Completion (Anticipated): December 1, 2023
• Study Completion (Anticipated): February 1, 2024

Study Registration Dates

• First Submitted: June 17, 2022
• First Submitted That Met QC Criteria: June 22, 2022
• First Posted (Actual): June 28, 2022

Study Record Updates

• Last Update Posted (Actual): May 9, 2023
• Last Update Submitted That Met QC Criteria: May 8, 2023
• Last Verified: May 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Cardiovascular Diseases; Vascular Diseases; Skin Diseases; Disease; Congenital Abnormalities; Hematologic Diseases; Hemorrhagic Disorders; Genetic Diseases, Inborn; Connective Tissue Diseases; Hemostatic Disorders; Skin Diseases, Genetic; Skin Abnormalities; Collagen Diseases; Syndrome; Ehlers-Danlos Syndrome
• Other Study ID Numbers: 21-5787.0

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No