Blood outgrowth endothelial cells as a patient-derived ex vivo model system to study degranulation mechanisms in storage pool disease

Despite the fact that platelet secretion defects are the most common amongst
inherited platelet function disorders, little is known about the mechanisms
responsible for platelet exocytosis. We hypothesize that individuals suffering
from congenital disorders that result in defective platelet secretory
mechanisms, such as presented in storage pool disease (SPD), (also) have
aberrant endothelial secretory responses.

Furthermore, there is no consensus about the best laboratory practice for
detecting platelet secretion defects and the current available tests have
several major limitations.

1. To study the mechanisms that control endothelial and platelet secretion
using blood outgrowth endothelial cells (BOECs) as an ex vivo model of
endothelial and platelet secretion, in order to identify new regulators of and
further unravel their secretory mechanisms

2. To investigate if mepacrine staining of platelets can be a robust and
accurate laboratory test for diagnosing δ-storage pool disease

Cross-sectional descriptive study coordinated at the Van Creveldkliniek (VCK)
of the University Medical Center Utrecht (UMCU) in collaboration with Sanquin
Research, Amsterdam.

This study will contribute to the knowledge on the mechanisms that control
endothelial and platelet secretion, which will have fundamental importance for
our understanding of secretory processes in these but also in other (blood)
cell types. Furthermore, we will evaluate a new methodology for detection of
platelet secretion defects. The participating patients will not benefit
directly from participation. However, the results of this study can lead to new
diagnostic tools and/or therapeutic strategies for hemostatic and immunological
disorders that are caused by secretory defects. The study consists of one visit
to the VCK for venipuncture. Risks imposed by participation are considered
negligible.