Predicting platelet age in an intelligent way

Platelets are small, anucleated cells with their primary physiological role to
repair vascular damage (hemostasis) and initiate thrombus formation in response
to vascular injury. During ageing platelets lose platelet surface glycoproteins
and proteins involving platelet granulation, secretion and regulated exocytosis
time as we have previously shown.

Diminished function due to storage, e.g. the platelet storage lesion (PSL), has
major impact on transfusion medicine. Also deficiency in platelet function or
count will lead to bleeding complications, like in patients with immune
thrombocytopenia (ITP). Predicting apparent platelet age will determine whether
platelets are relatively young and thus rapidly cleared, or older assuming due
to decreased production. Patients with rapid clearance may benefit more from
treatment with clearance inhibitors (glucocorticoids and Rituximab), where
patients with older platelets may benefit from treatment to enhance production
such as TPO-RA. In our preliminary in vitro studies we could separate young and
old platelets using novel platelet imaging techniques and artificial
intelligence techniques.

In this research proposal we will first characterize platelets in vivo in
patients with a platelet disorder (Lowe syndrome). Additionally we will
characterize young and old platelets in vivo in patients with acute myeloid
leukemia (AML) receiving chemotherapy. Results of this project will lead to
better understanding of platelets of patients with a platelet disorder (part
1), and will also generate new insights into treatment options for patients
with thrombocytopenia (part 2).

Primary Objective:
Part 1: to characterize platelets of patients with Lowe syndrome using
superresolution microscopy.
Part 2: to characterize platelet age in patients receiving chemotherapy for AML
using artificial intelligence techniques.

Secondary Objectives:
Part 1: to evaluate platelet function using flowcytometry and aggregometry.
Part 2: Not applicable

Single center observational study

The burden for Lowe patients in Part 1 is one blood draw during routine
clinical test. The amount of blood is based on the weight, with a maximum of
16mL. This is lower than the maximum amount of blood recommended (appendix 1).
The burden for clinical AML patients in Part 2 is 4,5mL blood draw during
routine clinical test at day 0, 3, 5 and 7 after chemotherapy. And also 1 blood
draw during repopulation, defined as first timepoint of increase of platelet
count and >10 days after platelet transfusion. Finally during steady state one
blood draw, defined as the time when platelet count >150x10E9/L.