Sickle Cell Disease
Conditions
Keywords
Hemorheology, Microfluidics, Blood viscosity, Red blood cell, Sickle cell disease
Brief summary
Numerous pathologies (sickle cell disease, thalassemia, spherocytosis, etc.) lead to changes in the rheological properties of the blood, in particular via alterations in the deformability of red blood cells. These alterations lead to circulatory complications of which an emblematic example is the sickle cell crisis which manifests itself by microcirculatory occlusions. Several authors suggest that the deformability of erythrocytes is a key parameter for the diagnosis and monitoring of patients. Numerous studies, especially in vitro, show that the mechanical properties of the red blood cell significantly influence its dynamics in flow (blood viscosity, distribution in capillary networks). Moreover, concerning the specific problem of vaso-occlusion, the proportion of the most rigid red blood cells is a determining factor of the probability of occlusion more than the average value of this rigidity which can hide great disparities. There is no clinically usable test to assess the alteration of the fine rheology of the red blood cell in a patient. Functional tests such as ektacytometry require heavy equipment and teams of specialized biologists; this technique is therefore only available in 3 biological reference centers in France. Mechanical phenotyping seems to be a potentially simpler and more accessible technique, and has already shown promising prospects in other nosological settings than red blood cell pathologies. Today, there is no specific marker of sickle cell vaso-occlusive crisis, nor marker of severity, that would be useful for pathophysiological understanding but also for clinical management.
Detailed description
This study aims to characterize the microfluidic flow and intra-erythrocyte viscosity of sickle cell red blood cells, and to identify specific biological phenotype or clinical severity profiles. The techniques used are microfluidic circuits for the study of flow and molecular rotors for the measurement of intra-erythrocyte viscosity, using deoxygenation cycles in order to model physio-pathological situations. The first part will allow the calibration of the microfluidic techniques used (microfluidic circuit and molecular rotors), testing blood from healthy subjects (without constitutional or acquired red blood cell pathology) and blood from SCD patients. The aim is to define the reproducibility and sensitivity of the techniques. A second part is aimed at establishing a rheological profile of the blood of patients with SCD in comparison with blood from control subjects, i.e. with other constitutional or acquired red blood cell pathology.
Interventions
OTHERBlood sample collection
Blood sample collection
Sponsors
University Hospital, Grenoble
Study design
Observational model
CASE_CONTROL
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
for healthy volunteers : 1. Patient age ≥ 18 years 2. With social care protection 3. Living donor recruited for kidney donation with normal blood count Inclusion Criteria for SDC patient : 1. Patient age ≥ 18 years 2. With social care protection 3. SCD patient with documented phenotype: SS, S°, S+, SC, SLepore, SOrab, SDPundjab, ASantilles... with or without specific treatment Inclusion Criteria for patient with a constitutional non-sickle cell disease of the red blood cell, or an acquired red blood cell disease : 1. Patient age ≥ 18 years 2. With social care protection 3. With any of the following conditions : 1. Patient being managed for anemia due to martial deficiency, and prior to oral or intravenous replacement therapy 2. Patient being followed for myeloproliferative syndrome at diagnosis, and prior to any specific treatment (hemodilution or hydroxycarbamide or other specific treatment) 3. A patient with a MCGRE other than a major sickle cell syndrome, whether or not under specific treatment 4. Hemoglobinopathy: transfusion-dependent or independent thalassemias (major or intermediate), thalassemias minor, heterozygous sickle cell trait A/S, other heterozygous hemoglobin variants (C, E, Lepore...), hyperaffine hemoglobin 5. Membrane disorders (hereditary spherocytosis) 6. Canalopathies (stomatocytosis with dehydrated or hyperhydrated erythrocytes, melanesian ovalocytosis...) 7. Enzyme deficiencies (G6PD, PK, GPI...)
Exclusion criteria
for all patients: 1. Patient age \< 18 years 2. Subject under guardianship, or subject deprived of freedom 3. Linguistic or literacy status not allowing for informed consent despite patient information in Easy to Read and Understand format 4. Known history of HIV, HTLV, syphilis, or positive serology and active viral hepatitis B or C. Additional
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Study of the intra-erythrocyte viscosity dispersion and rheological profile of red blood cells | 30 months | Measure of the intra-erythrocyte viscosity dispersion using molecular rotors technique, study of rheological profile of red blood cells in microfluidic circuit : measure of the speed of flowing, and DI deformability Index \[DI = (L-W)/(L+W)\] of each red blood cell, DI dispersion in each sample, in basal state and after exposure to deoxygenation cycles of blood SCD patients versus control subjects. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Study of the intra-erythrocyte viscosity dispersion and rheological profile of red blood cells | 24 months | Measure of the intra-erythrocyte viscosity dispersion using molecular rotors technique, study of rheological profile of red blood cells in microfluidic circuit : measure of the speed of flowing, and DI deformability Index \[DI = (L-W)/(L+W)\] of each red blood cell, DI dispersion in each sample, in basal state and after exposure to deoxygenation cycles in different conditions : congenital red blood cell disorders, acquired red blood cell disorders and clinical events (vasoocclusive crisis, pregnancy, infection). |
Contacts
Primary ContactCaroline MAKOWSKI, Md
Backup ContactBruna DUCOTTERD, CRA
Outcome results
None listed