Characterization of Bleeding Disorders in EDS

Study Overview
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Brief Summary
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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.

Official Title
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Disordered Bleeding in Ehlers Danlos Syndromes

Conditions
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EDS, Hypermobile Ehlers-Danlos Syndrome, Hypermobile EDS (hEDS), Vascular Ehlers-Danlos Syndrome, Vascular EDS (vEDS), Ehlers-Danlos Syndrome, Classical Ehlers-Danlos Syndrome, Classical EDS (cEDS)

Intervention / Treatment
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* Other: 20 ml venous blood collection


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Study Plan
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How is the study designed?
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Arms and Interventions

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

What is the study measuring?
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Primary Outcome Measures

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

Secondary Outcome Measures

| Outcome Measure | Measure Description | 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 |