Hereditary Spherocytosis and Vascular Function

Not Applicable

Completed

Interventions: Biological: blood sample
Diagnostic Test: Pulse wave velocity

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).

Recruitment & Eligibility

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).

Arm && Interventions

Group	Intervention	Description
Healthy individuals	blood sample	20 healthy subjets aged 6 years minimum will be included in this study. This is the control group.
Healthy individuals	Pulse wave velocity	20 healthy subjets aged 6 years minimum will be included in this study. This is the control group.
Patients with hereditary spherocytosis	blood sample	60 patients with hereditary spherocytosis will be included in this study.
Patients with hereditary spherocytosis	Pulse wave velocity	60 patients with hereditary spherocytosis will be included in this study.

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
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
Blood viscosity	Day 1	Blood viscosity (expressed in Pa.s) will be measured on a cone-plate viscosimeter, ektacytometry and light transmission, respectively.
Markers of erythrosis	Day 1	Markers of erythrosis (i.e., suicidal death of red blood cells) will be measured by flow cytometry
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).

Locations (2): Hôpital Edouard Herriot
🇫🇷
Lyon, France
Institut d'Hématologie et Oncologie PEdiatrique (iHOPe)
🇫🇷
Lyon, France