Temporal differences in membrane loss lead to distinct reticulocyte features in hereditary spherocytosis and in immune hemolytic anemia

Hereditary Spherocytosis: Evaluation of 68 Children

“…These proteins are employed in the attachment of the cytoskeleton to the membrane integral domain, so any deficiency or dysfunction in them results in a loss of surface area and leads to spheroidal, osmotically fragile erythrocytes [8,9]. It is impossible for these spherocytic, fragile erythrocytes to pass through the splenic sinusoids easily.…”

Clinical and hematologic features of 300 patients affected by hereditary spherocytosis grouped according to the type of the membrane protein defect

“…[10][11][12] The deficiency or dysfunction of any of these proteins, which are involved in the attachment of the cytoskeleton to the membrane integral domain, results in a loss of surface area and leads to spheroidal, osmotically fragile cells that are selectively trapped in the spleen. 13,14 The defective protein can be detected by sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE), which allows the identification of different subsets of patients; 3,15,16 although some HS subjects remain unclassified by this technique; 16,[17][18][19] efforts to identify the protein defect by genetic analysis in unclassified cases have been unsuccessful. 20 It is usually thought that the clinical phenotype of spectrin deficiency is more severe than that of band 3 deficiency, and that the level of residual spectrin inversely correlates with the severity of anemia.…”

Additional erythrocytic and reticulocytic parameters helpful for diagnosis of hereditary spherocytosis: results of a multicentre study

“…These lost proteins include the transferrin receptor, flotillin, Glut-4, CD47, actin, Hsc70, aquaporin-1 (AQP-1) and adhesion receptors such as β1-integrin [16]. In HS, the loss of cell surface area at the reticulocyte stage [9] could explain that one or multiple of these compounds normally stained by the fluorescent dye in the reticulocyte channel are less marked in cases of HS.…”

“…Furthermore, one previous study [9] showed that different mechanisms lead to reduced membrane surface area in hereditary spherocytosis and some forms of AIHA. Indeed, in HS, but not in AIHA, the surface area loss is already present at the circulating reticulocyte stage.…”

“…Some authors recommend automated red cell indices to predict or identify HS. Increased parameters such as reticulocytosis, % microcytes [5,2,6], combination of increased Mean Corpuscular Haemoglobin Concentration (MCHC) with increased red distribution width (RDW) [2,7] , combination of increased RDW with hyperdense cells (Hyperchromic cells) [2,8], combination of increased MCHC with increased hyperdense cells [2], decreased red cell and reticulocyte surface area [9], discordance between the Cell Haemoglobin Concentration Mean (CHCM) and MCHC [8] or Mean Spherized Corpuscular Volume (MSCV) lower than Mean Cell Volume (MCV) [10] are used for HS screening. However, most of these parameters are mean parameters and none of the tests is efficient for HS screening, especially in mild forms (without anaemia, reticulocytes <6% and bilirubin 17.4-34.2µM) or carriers of an asymptomatic trait (without anaemia, slight reticulocytosis (1.5-3.0%) and slightly reduced haptoglobin) [3].…”