Investigating red blood cell deformability of sickle cell patients who started therapy.

Sickle cell disease (SCD) is a hemoglobinopathy in which a single nucleotide
mutation in the beta-globin chain causes the formation of the abnormal
hemoglobin S (HbS). When HbS becomes deoxygenated it polymerises, resulting in
sickling of red blood cells (RBCs). These sickled RBCs have strongly reduced
deformability, leading to vaso-occlusive crises, multi organ failure and
chronic hemolytic anemia.
Hydroxyurea is the only approved drug for the treatment of sickle cell disease.
It increases the production of fetal hemoglobin (HbF), thereby lowering HbS
levels and, consequently, decreases sickling events. There is however no
accurate measurement of a dose-and-effect relation, other than the next
life-threatening crisis.
Altered red blood cell (RBC) deformability is a feature of many RBC disorders,
including SDC. It can be measured using the Lorrca (Laser-assisted Optical
Rotational Red Cell Analyzer) under varying circumstances. For instance, the
hypoxia-hyperoxia ektacytometry module of the Lorrca enables the measurement of
RBC deformability in response to changes in oxygen tension. This is
particularly relevant in the field of SCD. Variables known to be of influence
for sickling (e.g. HbF levels, presence of transfusion blood) can be studied by
using one single fully automated, operator independent test. We hypothesize
that this single test can determine an individual*s status and/or
susceptibility to sickling, and measure the effect of hydroxyurea therapy and
blood transfusion.
Besides this whole blood of newborns with SCD will be investigated to see if
there is a correlation between HbF (which decreases during the first 9 months
of life) and RBC deformability.

Investigating red blood cell deformability changes, during treatment, measured
with hyperoxia-hypoxia ektacytometry in sickle cell anemia patients, patients
with HbSC disease and patients with HbS-beta-thalassemia.

This study is a longitudinal observational study in which Lorrca measurements
and other blood tests will be performed at 4 different time points: before (1
time point) and during treatment (3 time points). Extra blood will be drawn at
baseline when therapy is started, at 1 month, 3 months and 6 months.
In case of neonates, timepoints will depend on regularly visits at the
outpatient clinic.

In case of blood transfusion there will be only 1 timepoint as this treatment
has an direct effect on Lorrca measurements.

In case of the baseline cohort there will be only 1 time point.

In case of patients receiveing a allogeneic HSCT of gene therapy before the
treatment, after 3 months and after 6 months blood will be drawn.

Generally, most SCD patients start hydroxyurea therapy already in childhood,
rarely in adult life. Therefore, the study group will mainly consist of
children who are currently not on hydroxyurea therapy, but are about to start.
Adults can also participate but will be scarce as they are already on
hydroxyurea therapy. The venipuncture will be combined with a routine visit and
routine venipuncture. The subjects will not directly benefit from this study.
However, this study may lead in the future to a better way to assess therapy
efficacy.

Physical discomfort is limited but may include bruising.