Integrative Diagnosis for SCD and Other RADs

Integrative Diagnosis of Sickle Cell Disease (SCD) and Other Rare Anemia Disorders (RADs) for Personalized Medicine

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.

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.

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