Hereditary Spherocytosis and Vascular Function (VASCUSPHERO)

Relationships Between Hemolysis, Erythrosis, Circulating Microparticles and Vascular Function in Patients With Hereditary Spherocytosis

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).

Study Overview

• Status: Completed
• Conditions: Hereditary Spherocytosis
• Intervention / Treatment: Biological: blood sample; Diagnostic test: Pulse wave velocity

• Study Type: Interventional
• Enrollment (Actual): 72
• Phase: Not Applicable

Contacts and Locations

Study Locations

• France
  • Lyon, France, 69437
    • Hopital Edouard Herriot
  • Lyon, France, 69373
    • Institut d'Hématologie et Oncologie PEdiatrique (iHOPe)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 2 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

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).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Healthy individuals; 20 healthy subjets aged 6 years minimum will be included in this study. This is the control group.	Biological: blood 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 test: Pulse wave velocity; Non-invasive measurement of pulse wave velocity between the carotid and femoral arteries with piezo-electric sensors.
Experimental: Patients with hereditary spherocytosis; 60 patients with hereditary spherocytosis will be included in this study.	Biological: blood 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 test: Pulse wave velocity; Non-invasive measurement of pulse wave velocity between the carotid and femoral arteries with piezo-electric sensors.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
measurement of pulse wave velocity (PWV)	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.	Day 1

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Hemogram	The hemogram is a complete blood count of the different cell types. All these measures are performed simultaneously on a standard hematology analyzer.	Day 1
Markers of hemolysis	These markers are measured simultaneously on a standard biochemistry analyzer	Day 1
Circulating microparticles	Circulating microparticles of various cell origin will be measured by flow cytometry	Day 1
Markers of erythrosis	Markers of erythrosis (i.e., suicidal death of red blood cells) will be measured by flow cytometry	Day 1
Blood viscosity	Blood viscosity (expressed in Pa.s) will be measured on a cone-plate viscosimeter, ektacytometry and light transmission, respectively.	Day 1
Red blood cell deformability	Red blood cell deformability will be measured simultaneously on a Lorrca ektacytometry (Laser-assisted Rotational Red Cell Analyser).	Day 1
Red blood cell aggregation	Red blood cell aggregation will be measured simultaneously on a Lorrca ektacytometry (Laser-assisted Rotational Red Cell Analyser).	Day 1

Collaborators and Investigators

• Sponsor: Hospices Civils de Lyon

Publications and helpful links

General Publications

• Casabianca M, Gauthier A, Nader E, Cannas G, Martin F, Martin M, Carin R, Boisson C, Guillot N, Merazga S, Renoux C, Bertrand Y, Garnier N, Hot A, Muniansi I, Halfon-Domenech C, Poutrel S, Joly P, Connes P. Red blood cell senescence and vascular function in patients with hereditary spherocytosis with and without splenectomy. Br J Haematol. 2024 May;204(5):e41-e44. doi: 10.1111/bjh.19444. Epub 2024 Apr 2. No abstract available.

Study record dates

Study Major Dates

• Study Start (Actual): August 26, 2020
• Primary Completion (Actual): August 26, 2022
• Study Completion (Actual): August 26, 2022

Study Registration Dates

• First Submitted: June 18, 2020
• First Submitted That Met QC Criteria: June 25, 2020
• First Posted (Actual): June 30, 2020

Study Record Updates

• Last Update Posted (Estimated): August 26, 2025
• Last Update Submitted That Met QC Criteria: August 20, 2025
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: vascular function; hemolysis; red blood cell; microparticles; Hereditary spherocytosis
• Additional Relevant MeSH Terms: Pathologic Processes; Genetic Diseases, Inborn; Hematologic Diseases; Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Anemia; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Pathological Conditions, Signs and Symptoms; Hemic and Lymphatic Diseases; Hemolysis; Spherocytosis, Hereditary; Investigative Techniques; Therapeutics; Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Surgical Procedures, Operative; Blood Specimen Collection; Diagnostic Techniques, Cardiovascular; Phlebotomy; Pulse Wave Analysis
• Other Study ID Numbers: 69HCL19_0949; 2019-A03203-54 (Other Identifier: ID-RCB)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No