Hereditary Spherocytosis
Conditions
Keywords
Hereditary spherocytosis, hemolysis, microparticles, vascular function, red blood cell
Brief summary
Background : Patients with hereditary spherocytosis (HS) are characterized by increased red blood cell (RBC) fragility and a loss of RBC deformability. While the clinical variability of the disease may be heterogenous from one patient to another, some studies reported the occurrence of vascular complications, notably in patients who have been splenectomized. Purpose : The aim of the study is to test the associations between the degree of vascular dysfunction and the extent of hemolysis, the amount of circulating microparticles, the level of erythrosis and the degree of RBC biophysical alterations. Abstract : Recent studies reported the occurrence of vascular complications in patients with HS, notably in patients who have previously been splenectomized. However, the exact reasons of these complications are unknown and no study investigated the vascular function in HS patients. Main objective Highlight the presence of altered vascular function in HS patients and test the relationships with the level of hemolysis and circulating microparticles. Secondary objectives To evaluate the associations between clinical severity and 1) the level of vascular dysfunction and 2) several biomarkers (hemolysis, hematological parameters, circulating microparticles, erythrosis, RBC biophysical properties).
Interventions
BIOLOGICALblood sample
6 tubes of 4 milliliters (ml) maximum (total: 24 ml) will be sampled for the measurements of the different biological markers. In case of the genetic mutation is already known, only 5 tubes will be collected (total: 20 ml).
DIAGNOSTIC_TESTPulse wave velocity
Non-invasive measurement of pulse wave velocity between the carotid and femoral arteries with piezo-electric sensors.
Sponsors
Hospices Civils de Lyon
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
6 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
Healthy controls: * age ≥ 6 years old * written, informed and signed consent by the healthy volunteer, or by both parents or legal guardian if the healthy volunteer is a minor * Healthy volunteer affiliated to a social security scheme or assimilated * Healthy volunteer not subject to any legal protection measure Patients with hereditary spherocytosis: * age ≥ 6 years old * Patient with hereditary or non-splenectomized spherocytosis * Written, informed and signed consent by the patient, or by at least one of the two parents or legal guardian if the patient is a minor * Patient affiliated to a social security scheme or assimilated * Patient not subject to any legal protection measure
Exclusion criteria
Healthy controls: * Pregnant or lactating woman * Subjects with hereditary spherocytosis or other characterized condition by chronic hemolysis * Subjects with known pathology affecting the vascular system * Blood donation (less than a month old) * Not affiliated to a social security scheme * Patient participating in another interventional research protocol that may interfere with this protocol (according to the investigator's judgment). Patients with hereditary spherocytosis: * Patient who received a blood transfusion in the 3 months preceding * Pregnant or lactating woman * Any disease or condition other than hereditary spherocytosis, chronic or not, likely to induce chronic or acute intravascular hemolysis * Patient participating in another interventional research protocol that may interfere with this protocol (according to the investigator's judgment).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| measurement of pulse wave velocity (PWV) | Day 1 | Vascular function (arterial stiffness) will be investigated by the measurement of pulse wave velocity (PWV). Vascular dysfunction will be defined by a PWV value higher than 6 meter/second (m/s) and 10 m/s in children and adults with HS, respectively. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Hemogram | Day 1 | The hemogram is a complete blood count of the different cell types. All these measures are performed simultaneously on a standard hematology analyzer. |
| Markers of hemolysis | Day 1 | These markers are measured simultaneously on a standard biochemistry analyzer |
| Circulating microparticles | Day 1 | Circulating microparticles of various cell origin will be measured by flow cytometry |
| Markers of erythrosis | Day 1 | Markers of erythrosis (i.e., suicidal death of red blood cells) will be measured by flow cytometry |
| Blood viscosity | Day 1 | Blood viscosity (expressed in Pa.s) will be measured on a cone-plate viscosimeter, ektacytometry and light transmission, respectively. |
| Red blood cell deformability | Day 1 | Red blood cell deformability will be measured simultaneously on a Lorrca ektacytometry (Laser-assisted Rotational Red Cell Analyser). |
| Red blood cell aggregation | Day 1 | Red blood cell aggregation will be measured simultaneously on a Lorrca ektacytometry (Laser-assisted Rotational Red Cell Analyser). |
Countries
France
Outcome results
None listed