Abstract
Mean values of hematological parameters are currently used in the clinical laboratory settings to characterize red blood cell properties. Those include red blood cell indices, osmotic fragility test, eosin 5-maleimide (EMA) test, and deformability assessment using ektacytometry to name a few. Diagnosis of hereditary red blood cell disorders is complemented by identification of mutations in distinct genes that are recognized “molecular causes of disease.” The power of these measurements is clinically well-established. However, the evidence is growing that the available information is not enough to understand the determinants of severity of diseases and heterogeneity in manifestation of pathologies such as hereditary hemolytic anemias. This review focuses on an alternative approach to assess red blood cell properties based on heterogeneity of red blood cells and characterization of fractions of cells with similar properties such as density, hydration, membrane loss, redox state, Ca2+ levels, and morphology. Methodological approaches to detect variance of red blood cell properties will be presented. Causes of red blood cell heterogeneity include cell age, environmental stress as well as shear and metabolic stress, and multiple other factors. Heterogeneity of red blood cell properties is also promoted by pathological conditions that are not limited to the red blood cells disorders, but inflammatory state, metabolic diseases and cancer. Therapeutic interventions such as splenectomy and transfusion as well as drug administration also impact the variance in red blood cell properties. Based on the overview of the studies in this area, the possible applications of heterogeneity in red blood cell properties as prognostic and diagnostic marker commenting on the power and selectivity of such markers are discussed.
Highlights
Our understanding of red blood cells (RBCs) evolved from acknowledgment of the basic and fundamental role of these cells as key players in gas exchange to the state where we assign multiple complex functions related to sensing and signaling, maintenance of homeostasis of pH and redox state and participation in control of vascular tone, clotting (Andrews and Low, 1999; Bernhardt et al, 2019), and other processes (Helms et al, 2018; Pernow et al, 2019).Heterogeneity of Red Blood CellsBroadening of RBC functions was accompanied with our awareness of complexity of the cellular architecture and biochemistry
This review focuses on an alternative approach to assess red blood cell properties based on heterogeneity of red blood cells and characterization of fractions of cells with similar properties such as density, hydration, membrane loss, redox state, Ca2+ levels, and morphology
As we recognize the existence of multiple fractions of RBCs that are functionally different from each other, we feel a growing need to unravel the nature of these differences, their causes and the potential information hidden in RBC heterogeneity on systemic distress and pathology
Summary
Our understanding of red blood cells (RBCs) evolved from acknowledgment of the basic and fundamental role of these cells as key players in gas exchange to the state where we assign multiple complex functions related to sensing and signaling, maintenance of homeostasis of pH and redox state and participation in control of vascular tone, clotting (Andrews and Low, 1999; Bernhardt et al, 2019), and other processes (Helms et al, 2018; Pernow et al, 2019).Heterogeneity of Red Blood CellsBroadening of RBC functions was accompanied with our awareness of complexity of the cellular architecture and biochemistry. Our understanding of red blood cells (RBCs) evolved from acknowledgment of the basic and fundamental role of these cells as key players in gas exchange to the state where we assign multiple complex functions related to sensing and signaling, maintenance of homeostasis of pH and redox state and participation in control of vascular tone, clotting (Andrews and Low, 1999; Bernhardt et al, 2019), and other processes (Helms et al, 2018; Pernow et al, 2019). As we recognize the existence of multiple fractions of RBCs that are functionally different from each other, we feel a growing need to unravel the nature of these differences, their causes and the potential information hidden in RBC heterogeneity on systemic distress and pathology. Heterogeneity of stored or transfused RBCs is a broad topic out of the scope of this review
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