Hereditary blooddisorder Sicklecell anaemia
Conditions
Interventions
None listed
Sponsors
Academisch Medisch Centrum
Eligibility
Age
2 Years to 99 Years
Inclusion criteria
Inclusion criteria: 1.Sickle cell disease patients (age >= 6 years) with high performance liquid chromatography (HPLC) confirmed diagnosis of HbSS, HbSβ0-thalassemia, HbSC or HbSβ+- thalassemia genotype 2. Willing and able to provide written informed consent 3. For the steady state/transfusion/hydroxyurea subgroup: visiting outpatient clinic 4. For the subgroup of patients during painful crisis: inclusion should be performed within 36 hours of admission to the hospital
Exclusion criteria
Exclusion criteria: 1. Unable to sign informed consent 2. VOC within 4 weeks of the outpatient clinic visit (steady state subgroup) 3. Pregnancy 4. Active cancer 5. Chronic HIV infection 6. Use of immunosuppressive drugs
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Primary endpoint of this studie is the difference in activity and phenotypes of neutrophils in patients with sickle cell disease compared to those of healthy controls. We aim to address the following questions: - Is neutrophil activity (as measured by flow cytometry and in vitro release of NETs) altered in patients with SCD and does this differ in various circumstances, such as VOC/steady state? - Which subtypes (anti-inflammatory/pro-angiogenic (N2) vs. pro-inflammatory (N1)) of neutrophils are present in steady state SCD? Is there a relation with hemolytic vs. vaso-occlusive phenotype of SCD? - How does the neutrophil phenotype alter during vaso-occlusive crisis with increased inflammation and hypoxia as a result of this vaso-occlusion? | — |
Secondary
| Measure | Time frame |
|---|---|
| - The effect of hydroxyurea and red blood cell transfusion on neutrophil phenotype and activity in SCD - The relation of neutrophil phenotype and activity with iron overload in transfused patients - Formation of aggregates between neutrophils and platelets - To elucidate and identify stimulating signals in the vascular microenvironment that drive phenotypic switching of neutrophils. Potential candidates are inflammatory cytokines, danger signals such as cell-free heme and labile iron and pro-angiogenic factors. - We will identify prime candidates that correlate with disease severity and neutrophil phenotypic changes in in vitro blocking experiments. - Is sickle red blood cell deformability as measured by Oxygen-scan (LORRCA) associated with neutrophil activation and phenotype? - To evaluate the relation between the above mentioned markers during painful crisis and clinical parameters of disease severity (pain score, duration of hospitalization, time to next crisis/readmission and other acute complications of painful crisis such as ACS). | — |
Countries
Netherlands
Outcome results
None listed