Red cell membrane disorders: structure meets function

Abstract

The mature red blood cell (RBC) is lacking a nucleus and organelles characteristic of most cells, but it is elegantly structured to perform the essential function of delivering oxygen and removing carbon dioxide from all other cells while enduring the shear stress imposed by navigating small vessels and sinusoids. Over the past several decades the efforts of biochemists, cell and molecular biologists, and hematologists have provided an appreciation of the complexity of RBC membrane structure, while studies of the RBC membrane disorders have offered valuable insights into structure-function relationships. Within the last decade advances in genetic testing and its increased availability have made it possible to substantially build upon this foundational knowledge. Although disorders of the RBC membrane due to altered structural organization or due to altered transport function are heterogeneous, they often present with common clinical findings of hemolytic anemia. However, they may require substantially different management depending on the underlying pathophysiology. Accurate diagnosis is essential to avoid emergence of complications or inappropriate interventions. We propose an algorithm for laboratory evaluation of patients presenting with symptoms and signs of hemolytic anemia with a focus on RBC membrane disorders. Here we review the genotypic and phenotypic variability of the RBC membrane disorders in order to raise the index of suspicion and highlight the need for correct and timely diagnosis.

Autoimmune Hemolytic Anemia in the Pediatric Setting

“…Blood smear review was remarkable for polychromasia and occasional spherocytes and microspherocytes ( Figure 1 ). Osmotic gradient ektacytometry was compatible with spherocytosis showing mildly increased Omin and decreased EImax [ 11 ], a picture that can be seen with w-AIHA when a significant percentage of the patient’s RBCs lose membrane surface area and become spherocytes. The super-Coombs test was sent to a referral testing center which detected low-affinity IgG on the patient’s RBCs when the cells were washed at 4 °C with low ionic strength solution (LISS), demonstrating his diagnosis as “(conventional) DAT-negative” w-AIHA.…”

Automated Oxygen Gradient Ektacytometry: A Novel Biomarker in Sickle Cell Anemia

“…Ektacytometry is a technique for measuring RBC deformability that is used for the diagnosis of RBC cytoskeleton and hydration disorders such as hereditary spherocytosis and xerocytosis ( Bessis et al, 1980 ; Da Costa et al, 2016 ; Risinger and Kalfa, 2020 ). In this technique, RBCs suspended in a liquid of known viscosity are subjected to increasing shear stress, or in the case of osmotic gradient ektacytometry (osmoscan), RBCs are suspended in a medium of varying osmolality and subjected to a steady shear stress.…”

The Post-Storage Performance of RBCs from Beta-Thalassemia Trait Donors Is Related to Their Storability Profile

“…The same was also true for donors carrying common single nucleotide polymorphisms in the N-terminus of band-3 [26]. The specialized spectrin-based RBC cytoskeleton and its numerous linkages to membrane proteins allow the cell to reversibly deform while passing through the narrow capillaries, while a variety of mutations in the genes of the proteins involved lead to hemolytic anemias in humans [27]. Non-muscle myosin II has been also associated with the control of the curvature and deformability-a biophysical marker of RBC fragility [28]-of cells with either actin-or spectrin/actin-based cytoskeletons [29,30].…”