1. To compare the platelet function between healthy controls and patients with ET under both static and dynamic conditions. 2. To study the effects of anagrelide and hydroxyurea on platelet function. 3. To study the intrinsic platelet activation…
ID
Source
Brief title
Condition
- Platelet disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The primary study parameters of this study are;
1. Platelet reactivity (FACS analysis - static conditions)
2. Platelet aggregate formation (perfusion model - dynamic conditions)
Secondary outcome
The secondary study parameters of this study are;
1. The effect of in vitro addition of anagrelide, BCH4426 (the metabolite of
anagrelide) and hydroxyurea on the platelet reactivity.
2. Markers of systemic platelet activation
- Soluble P-selectin (sPsel)
- Soluble CD-40 ligand (sCD40L)
- Regulated upon Activation, Normal T cell Expressed and Secreted (RANTES)
- Neutrophil Activating Protein-2 (CXCL7)
- Microparticles
- Von Willebrand Factor (vWF)
3. Markers of systemic coagulation activation
- Prothrombin fragment 1+2
- Thrombin-Antithrombin (TAT)-complexes
- Fibrine monomers
- D-dimers
4. Platelet-monocyte complex formation
Background summary
The pathogenesis of thrombosis in Essential Thrombocytosis (ET) is not fully
understood. The clinical manifestations of ET varies from asymptomatic to life
threatening thrombosis. Cytoreductive therapy with hydroxyurea or anagrelide
has shown to reduce platelet count, but the effect on platelet function has not
been delineated. We aim to study the effects of ET on platelet function and the
multifactorial thrombotic environment and evaluate the effect of cytoreductive
therapy. A better understanding of this effect might benefit treatment options
or risk assessment of thrombosis and bleeding in the future.
Study objective
1. To compare the platelet function between healthy controls and patients with
ET under both static and dynamic conditions.
2. To study the effects of anagrelide and hydroxyurea on platelet function.
3. To study the intrinsic platelet activation routes in ET and the effects of
cytoreductive therapy on these routes.
Study design
Monocenter observational study; cross sectional for group 1, 2, 3 and 4 and a
prospective cohort study for group 5 and 6.
Study burden and risks
This study will contribute to the knowledge of platelet function in ET and the
effect of cytoreductive therapy on this function. Improved insights may lead to
improved treatment strategies and a better risk assessment of thrombosis and
bleeding.
The results of this study will not be directly beneficial for the participating
patients. Adverse events are not expected to occur in this study. One to three
visits to the hospital (according to the study group) is requested when
participating and a total amount of 35.5-106.5ml of blood is donated
respectively. The risk of venapuncture is considered to be very low.
Heidelberglaan 100
3584 CX Utrecht
NL
Heidelberglaan 100
3584 CX Utrecht
NL
Listed location countries
Age
Inclusion criteria
- Essential Thrombocytosis, diagnostic criteria met by the WHO criteria.
- According to the studied patient group, included patients will either use no cytoreductive therapy, or already use hydroxyurea or anagrelide. Or they will start treatment with hydroxyurea or anagrelide within two months.
- Age18 years or older
Exclusion criteria
- Use of medication that is known to influence platelet function (other than acetylsalicylic acid), s.a. clopidogrel, dipyridamole and NSAIDs (Non-Steroidal Anti-Inflammatory Drugs) within 14 days prior to inclusion and during follow up.
Design
Recruitment
metc-ldd@lumc.nl
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| CCMO | NL35936.041.11 |