Anemia Due to Membrane Defect, Congenital Dyserythropoietic Anemia (CDA), Enzyme Disorder; Anemia, Hemoglobin Disorder, Rare Anemia Disorders, Sickle Cell Disease, Spherocytosis, Hereditary, Stomatocytosis, Thalassaemia
Conditions
Keywords
SICKLE CELL DISEASE, RARE ANEMIA DISORDERS, PERSONALIZED MEDICINE, DIAGNOSIS, EKTACYTOMETRY
Brief summary
INTEGRA aims at enabling personalized medicine for RHADs patients by the establishment of an integrative diagnostic approach based on deep phenotypic and genetic characterization through combining new generation methodologies.
Detailed description
Objectives: * To assess the prognostic value of LoRRca (ektacytometry) as biomarker providing information of SCD/RADs patients severity * To investigate the correlation between LoRRca parameters and SCD/RADs patients genetic and phenotypic characterization. * To identify genetic modifiers of RADs both new and previously described by GWAS as markers for prognosis and clinical course based on genomics approach. * To establish an innovative algorithm for RADs patients characterization based on the integration of data generated through the analysis of genetic modifiers and the RBCs rheological properties by LoRRca profiles and microfluidics data in combination with RADs patients' clinical manifestations and treatments. * To model the progression of RADs in a spleen-like filtering unit using microfluidic technologies to develop a novel diagnostic device for prognosis and patients' stratification. This device will be used for the characterization under flow of rheological and mechanical properties of single RBCs. * To translate the results on a clinical practice recommendation for management of RADs patients endorsed by European Hematology bodies as ERN-EuroBloodNet and/or the European Hematology Association for its wide dissemination.
Interventions
GENETICAnalysis of genetic modifiers
Genetic modifiers for rare anemia disorders will be analyzed through massive sequencing.
DIAGNOSTIC_TESTDisease phenotyping
Peripheral blood samples will be used for conventional phenotyping characterization including among others: RBCs morphology, fragility osmotic test, hemoglobin fraction and quantification, hemoglobin stability test, EMA binding test, RBC enzymes quantification assay, RBC rheological properties through Lorrca Maxsis Osmoscan/Oxygescan (Lorrca®)
Sponsors
Hospital Clinic de Barcelona, Barcelona, Spain
Institute for Bioengineering of Catalonia
Hospital Arnau de Vilanova, Lleida (Spain)
Hospital Universitari Vall d'Hebron Research Institute
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Healthy volunteers
No
Inclusion criteria
* Patients sustaining a confirmed or suspected diagnosis of an hereditary rare hemolytic anemia: * Sickle cell disease * Thalassemic syndromes * Congenital dyserythropoietic anemia * Enzymopathy * Unstable Hemoblogin / Altered oxygen affinity * Hereditary stomatocytosis * Hereditary pyropoikilocytosis * Hereditary spherocytosis with severe anemia (\<8 g/dL) or inconclusive diagnosis: * Patient with chronic hemolytic anemia and red cell smear compatible, but with: * EMA binding test: inconclusive or negative * Genetic testing: no definitive diagnosis (VUS or no findings) * Not transplanted or undergoing gene therapy at the time of inclusion. Patients with graft failure without a new transplant may be included.
Exclusion criteria
* Carrier traits in autosomal recessive hereditary anemias
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| To assess the prognostic value of LoRRca ektacytometry as biomarker providing information of SCD/RADs patients severity | Through study completion, an average of 2 year | Severity was assesed as the occurence of: * Vaso-occlusive events (VOEs) in the last 24 months * Kidney injury (defined according to KDIGO guidelines) * Retinopathy (defined as proliferative and non proliferative) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| To investigate the correlation between LoRRca ektacytometry parameters and SCD/RADs patients genetic and phenotypic characterization. | Through study completion, an average of 2 year | Genomic data will be generated using a targeted next-generation sequencing (tNGS) approach. Means, medians, standard deviations (SD), ranges and percentages were calculated using SPSS software (version 20, IBM SPSS Statistics, Chicago, IL, USA). Spearman's rank correlation was used to assess associations between variables. For comparing variables with two categories, either a student's t-test or a Mann-Whitney U test was performed, when appropriate. When the variable had more than two categories, an ANOVA or Kruskal Wallis test was used. A p value \<0.05 was considered statistically significant. |
Countries
Spain
Contacts
Primary ContactMar Mañú Pereira PhD
Outcome results
None listed