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Blood Outgrowth Endothelial Cells (BOECs) and Megakaryocytes (MKs) for in vitro studies of hemostatic and secretory functio

Recruiting
Conditions
Bleeding disorders
Registration Number
NL-OMON24571
Lead Sponsor
Erasmus MC
Brief Summary

Not available

Detailed Description

Not available

Recruitment & Eligibility

Status
Recruiting
Sex
Not specified
Target Recruitment
300
Inclusion Criteria

Patients
???? Prior diagnosis of VWD, low VWF, inherited platelet function defects, bleeding of unknown
cause or genetic disorders in which dysfunction of the secretory pathway has been
implicated in disease pathogenesis.
???? For patients =16 years old; written informed consent
???? For patients 12-15 years old; written informed consent from both the patient and their
parent(s)/legal guardian(s)
???? For patients <12 years old; written informed consent from their parent(s)/legal guardian(s)

Family members
???? Age 18 years or older
???? Family member of a patient with VWD, low VWF, inherited platelet function defects,
bleeding of unknown cause or genetic disorders in which dysfunction of the secretory
pathway has been implicated in disease pathogenesis.
???? Family members may or may not be affected.

Healthy controls
???? Age 18 years or older
???? Not previously diagnosed with VWD, low VWF, inherited platelet function defects, bleeding
of unknown cause or genetic disorders in which dysfunction of the secretory pathway has
been implicated in disease pathogenesis.

Exclusion Criteria

A potential subject who meets any of the following criteria will be excluded from participation
in this study:
???? Unable to give written informed consent.
???? Use of medication that can compromise platelet function or hemostasis.

Study & Design

Study Type
Interventional
Study Design
Not specified
Primary Outcome Measures
NameTimeMethod
1. To establish optimized approaches for the isolation and characterization of BOECs, CD34+-<br>derived MKs, iPSC- ECs and iPSC-MKs.<br>2. Dissect the cellular mechanisms that control endothelial and platelet (secretory) function,<br>thereby understanding the pathophysiology of bleeding disorders and the genetic control of<br>VWF secretion using BOECs, platelets, CD34+-derived MKs, iPSC- ECs and iPSC-MKs.<br>3. To develop in vitro methods to introduce or correct (disease-causing) mutations in regulators<br>of endothelial or platelet function in BOECs or iPSC-derived ECs/MK using CRISPR-mediated<br>genome engineering.
Secondary Outcome Measures
NameTimeMethod
The study is a basic science, experimental in vitro study that requires the sampling of venous peripheral blood of the participants.
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