Erythrocyte Vesiculation In Hereditary Haemolytic Anaemias

Abstract

Hereditary haemolytic anaemia is any of a heterogeneous group of anaemias characterised by increased destruction/haemolysis of erythrocytes because of inherited erythrocyte membranopathies, enzymopathies, or haemoglobinopathies. The affected erythrocytes, of normal morphology or not, are more fragile, less deformable, and more susceptible to shear and oxidative damages. Erythrocytes, as most of eukaryotic cells, constitutively release phospholipid extracellular vesicles in vitro and in vivo in a process known as vesiculation. These extracellular vesicles embrace a heterogeneous group of vesicles of different sizes and intracellular origins. They are described in literature as exosomes if they are of endosomal origin or as microvesicles if vesicles are formed by a one-step budding process directly from the plasma membrane. Extracellular vesicles contain a multitude of bioactive molecules which are implicated in intercellular communication and in different biological and pathophysiological processes. Mature erythrocytes release mainly microvesicles. In hereditary haemolytic anaemias, the underlying diverse molecular defects alter and determine erythrocyte vesiculation, which results in shedding microvesicles of different compositions and concentrations. Despite extensive research into erythrocyte biochemistry and physiology, little is known about the deformability of erythrocytes and their vesiculation in hereditary haemolytic anaemias. Moreover, the impact of erythrocyte-derived microvesicles on the pathophysiology of hereditary haemolytic anaemias is not completely assessed. In this review, we discuss recent progress in understanding extracellular vesicles biology, with a focus on erythrocyte vesiculation. Also, we review recent scientific findings about the molecular defects of hereditary haemolytic anaemias, and their correlation with erythrocyte deformability and vesiculation. Integrating the bio-analytical findings about abnormalities of erythrocytes and their microvesicles may be critical for a better understanding of the pathophysiology of hereditary haemolytic anaemias.