1. To investigate if PMN of patients with sickle cell disease are prone to form NET when compared to PMN of healthy controls.2. To investigate if red blood cells of sickle cell disease patients promote NET formation of PMN in sickle cell patients as…
ID
Source
Brief title
Condition
- Haemoglobinopathies
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
n.a.
Secondary outcome
n.a.
Background summary
Sickle cell disease is a congenital disorder of the hemoglobin molecule
of the red blood cell. Patients are characterized by chronic hemolysis, chronic
anaemia and admissions for painful vaso-occlusive crises. The origination of a
painful crisis is a complex and multifactorial. Processes that are involved
included a reduced bioavailability of NO, activation of the coagulation system,
origination of oxidative stress, increased circulating inflammatory mediators
and white blood cells, especially neutrophils.
Recently we described increased circulating markers of neutrophil extracellular
traps (NET) in sickle cell disease patients during painful crisis. We observed
the highest values in patients who developed complications during painful
crisis and/or had the longest hostpiatlisation for painful crisis. However, it
remains unclear if these NET truly play an active role in the pathophysiology
of sickle cell painful crisis or painful crisis related complications or maybe
the circulating markers reflect an epiphenomenon. Experimental research will be
necessary to further investigate this phenomenon.
Study objective
1. To investigate if PMN of patients with sickle cell disease are prone to form
NET when compared to PMN of healthy controls.
2. To investigate if red blood cells of sickle cell disease patients promote
NET formation of PMN in sickle cell patients as well as in PMNs of healthy
volunteers.
3. To investigate of plasma of sickle cell disease patients during painful
crisis is toxic to endothelial and parenchymal cells, and to explore if this is
due to extracellular neutrophil chromatin and proteases present in plasma.
Study design
This study had an experimental desing. Blood will be drawn by venapuncture from
healthy volunteers, sickle cell disease patients during steady state and sickle
cell patients during painful crisis. Neutrophils will be isolated from fresh
blood and used in different experiments. Blood plasma will also be investigated
in different experimental designs. Obtained results will be compared and
similarities as well as differences described.
Study burden and risks
No extra burden or risk is expected from this study.
Meibergdreef 9
Amsterdam 1105AZ
NL
Meibergdreef 9
Amsterdam 1105AZ
NL
Listed location countries
Age
Inclusion criteria
For patients:
1. High performance liquid chromatography confirmed diagnosis of HbSS, HbSC, HbS*0- or HbS*+-thalassemia genotype in SCD patients. 2. Written informed consent by the patient. 3.18 years and older
For healthy volunteers:
1. Age * 18 years; 2. WHO performance score 0; 3. healthy race-matched family member or acquaintance
Exclusion criteria
For patients
1. HbSC or HbS*+- thalassemia genotype . 2. Pregnancy 3. Active cancer 4. Chronic HIV infection 5. Recent vaso-occlusive crisis (< 1 months) 6. Chronic transfusion therapy 7. Recent blood transfusion (< 3 months)
For healthy volunteers:
Carrier of sickle cell gene or other hemoglobinopathy
Design
Recruitment
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 | NL47497.018.13 |