bloedarmoede heriditary hemolytic anaemia
Conditions
Interventions
None listed
Sponsors
Universitair Medisch Centrum Utrecht
Eligibility
Age
2 Years to 99 Years
Inclusion criteria
Inclusion criteria: Patient suffering from HHA, based on the following criteria; • A proposed RBC ion homeostasis disturbance due to a primary cause; membrane defects (spherocytosis, stomatocytosis) of the red blood cell (previously diagnosed by with a decreased EImax detected by osmotic gradient ektacytometry, or altered osmotic fragility, or altered EMA-binding test, or mutations found in SPTA1, SPTB, SLC4A1, ANK1, EPB41, EPB42, PIEZO1, RHAG. • A proposed RBC ion homeostasis disturbance due to a secondary cause; hemoglobinopathies (sickle cell anaemia, thallasemia) or enzymopathies of the red cell (previously diagnosed by detection of HbA2, HbF, HbS, HbE, HbD, HbC by electrophoresis, or decreased enzyme activity in red blood cell enzymes (PK, HK, G6PD, GPI, F-ALD, TPI, PGK, BPGM, GSR), or mutations found in HBA1, HBA2, HBB, PFKM, PGK1, G6PD, GPI1, HK1, PKLR) • Hemolytic anemia due to an unknown cause; patients previously screened for iron deficiency anaemia and other forms of nutritional deficiency anaemia, anaemia due to chronic illnesses or infection, membrane defects of the red cell, hemoglobinopathies and/or enzymopathies, without the detection of a (molecular) cause for the haemolytic anaemia. - Biological parent of a patient suffering from haemolytic anaemia due to an unknown cause
Exclusion criteria
Exclusion criteria: - Transfusion (erythrocyte concentrate) received in the last 90 days - For children: body weight
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| o Routine red blood cell characteristics (cytology) o Red blood cell morphology o Routine chemistry analysis; iron, ferritin, transferrin, vitamin B12, serum folate and haptopglobin levels o Eosin-5-maleimide (EMA) binding on surface of red blood cells o Osmotic fragility o Osmotic gradient ektacytometry (LoRRca MaxSis) o Deformability (LoRRca MaxSis) o Intracellular Na+ and K+ levels o Flow cytometric analysis of red blood cells: phosphatidyl serine exposure, CD47, band3, CD71, CD235a, intracellular Ca2+ o Glutathione measurement: ratio between GSH/GSSG o Surface protein expression of RBC microvesicles o Quantity and size distribution of RBC microvesicles o Conductance and patch-clamp measurements of red blood cells o Calcium homeostasis after chemical stimulation of red blood cells o Hemoglobin oxygen affinity o Red blood cell density; Percoll and filtration o ATP levels o DNA analysis (Next Generation Sequencing) | — |
Secondary
| Measure | Time frame |
|---|---|
| o Development of an optical sorting device with scanning ion conductance microscope (end points: (1) percentage sorted and/or percentage of interesting red cells based on morphology and/or fluorescent probes and (2) symmetry of (sorted) red cells measured with SICM). | — |
Countries
Netherlands
Outcome results
None listed