To examine the determinants of survival of donor RBCs in SCD patientsTo look into the effect of transfusion on the innate immune system of sickle cell patients, in particular, the phenotype of the neutrophils.
ID
Source
Brief title
Condition
- Red blood cell disorders
- Blood and lymphatic system disorders congenital
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
- Survival of donor RBCs in top up and exchange transfusions in SCD patients 4
weeks post-transfusion
- Effects of patient-derived factors (genotype, HbS%, hemolysis, endothelial
activation (proVWF/VWF ratio), inflammation, neutrophil activity/phenotype) on
donor RBC survival
Secondary outcome
- Phenotypic changes in endogenous and donor RBCs after transfusion in SCD
patients (1 hour, 24 hours, 1 week, 2 weeks, 3 and 4 weeks post-transfusion) as
compared to pre-transfusion
- Oxidative stress in endogenous/donor RBCs after transfusion in SCD patients
as expressed by intracellular metabolomics (1 hour, 24 hours, 1 week, 2 weeks,
3 weeks and 4 weeks post-transfusion)
- Immediate and late effects of transfusion on neutrophil activity and
phenotype in SCD patients (1 hour, 24 hours, 1 week and 2 weeks
post-transfusion) as compared to pre-transfusion values
- Survival of endogenous RBCs 1, 2 and 4 weeks after transfusion measured by
the ratio of glycine-15N and glycine 14N in heme
Background summary
Red blood cell (RBC) transfusions are currently one of the most important
therapeutic options for patients with sickle cell disease. Widespread
variability in survival of transfused RBCs has been described in literature,
both between different patients and within a patient over time. The mechanisms
causing this variability in donor RBC survival in SCD patients are largely
unknown. Possible factors influencing donor RBC survival in SCD patients are
oxidative stress, chronic inflammation with exacerbations during VOCs,
neutrophil activity/phenotype and endothelial activation. It is important
improve our understanding of these inter- and intra-individual differences in
donor RBC survival and the mechanisms behind them, as it might provide novel
targets for therapeutic strategies to improve the survival of transfused RBCs.
Study objective
To examine the determinants of survival of donor RBCs in SCD patients
To look into the effect of transfusion on the innate immune system of sickle
cell patients, in particular, the phenotype of the neutrophils.
Study design
Longitudinal observational cohort study. At seven different time points (before
transfusion, 1 hr, 1 day, 1 week, 2 weeks, 3 weeks and 4 weeks after
transfusion), data and blood samples will be collected. Furthermore patients of
>=12 years old will be asked to take 2 grams of 15N-glycine, dissolved in 30 mL
of water orally just before the transfusion.
Study burden and risks
Very little is known about the mechanisms causing variability in donor RBC
survival in SCD patients. Increased knowledge on this subject might provide
novel targets for therapeutic strategies to improve the survival of transfused
RBCs. Therefore a study in this population is essential. Risk of participation
is considered to be very small, as it will only consist of approximately five
additional blood drawings (maximum three additional blood drawings for
children). Blood drawings will be combined as much as possible with sample
collection for diagnostic purposes. Furthermore, patients of 12 years or older
are asked to take the stable isotope 15N-glycine (non-investigational product)
once. Stable isotopes have been used safely for research purposes in adults and
children for years. Since stable isotopes have the same atomic number, but
differ in mass number, they can be used to safely label erythrocytes.
Meibergdreef 9
Amsterdam 1105 AZ
NL
Meibergdreef 9
Amsterdam 1105 AZ
NL
Listed location countries
Age
Inclusion criteria
Sickle Cell Disease
>=6 years old
Clinical need for an erythrocyte transfusion
Exclusion criteria
- No informed consent
- Pregnancy, self-reported
- Active cancer
- Chronic of acute HIV infection
- Comorbid autoimmune/inflammatory disease
- Pre-operative incidental transfusion
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 | NL80752.018.22 |