Among patients with sickle cell disease (SCD), extracellular vesicles (EVs) may both be effective biomarkers and function as bioeffectors, according to research published in Frontiers in Medicine.

SCD, an autosomal disorder, affects more than 3 million people worldwide. The condition is linked with both chronic and acute anemia, which may, respectively, affect a patient’s organs, and can be life threatening.

Even among patients with the same SCD subtypes, however, there is a high degree of variation in clinical presentation. In this paper, researchers explored previously published data to evaluate whether, among patients with SCD, EVs are markers of cellular activation or alteration and/or bioeffectors that modulate pathophysiology.

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Previous research has suggested that EVs, which are cell-derived particles without a nucleus, are both biomarkers in SCD and may affect the disease’s pathophysiology, leading to variation in clinical presentation among patients. EVs are, furthermore, categorized into small EVs and medium/large EVs, and the latter have a higher plasma concentration among patients with SCD than in healthy individuals.

Medium/large EVs derived from red blood cells, the authors noted, can affect monocytes, macrophages, and endothelial cells in a way leading to inflammation. Small EVs, which have also been found in greater plasma concentration in patients with SCD, can also damage endothelial cells. Murine studies suggest, furthermore, that small EVs may play a role in lung vaso-occlusion.

“While high plasma levels of EVs have been reproducibly described, uncertainties remain about their cellular origins,” the authors wrote. “Nevertheless, these vesicles, both [small] EVs and [medium/large] EVs, are able to modulate key processes of SCD pathophysiology and are therefore bio-effectors in SCD.” They suggested that the evaluated data warrant further study.


Nader E, Garnier Y, Connes P, Romana M. Extracellular vesicles in sickle cell disease: plasma concentration, blood cell types origin distribution and biological properties. Front Med (Lausanne). 2021;8:728693. doi:10.3389/fmed.2021.728693