Microvesicles Measurement Could Detect Vascular Injury in Sickle Cell Disease Patients

Assessing disease severity in sickle cell disease (SCD) remains challenging, especially when trying to predict hemolysis, vascular injury, and risk of complications such as vaso-occlusive crises. Current markers like lactate dehydrogenase (LDH) can signal hemolysis but do not fully explain underlying mechanisms. Researchers have now identified circulating microvesicles (MVs) as a potential tool to assess vascular injury and severity in SCD, offering a new biomarker pathway for clinical evaluation.

In a study conducted at Institut Pasteur de Tunis (Tunis, Tunisia), researchers recruited individuals with homozygous SCD alongside healthy controls to investigate whether MV levels correlated with disease severity. The researchers analyzed plasmatic MVs using flow cytometry. They measured MV subtypes derived from red blood cells (RMVs), platelets (PMVs), and endothelial cells (EMVs), and evaluated associations between these levels and markers of severity, including hemoglobin, fetal hemoglobin, LDH, and clinical severity scores.

Image: Sickle cell disease patients with higher levels of RMVs, AMVs, and EMVs were found to have more severe disease (Photo courtesy of Adobe Stock)

Peripheral blood samples were collected from all participants, and complete blood counts and hemoglobin electrophoresis were performed. A total of 68 SCD patients and 62 healthy donors were included, with 42 SCD patients receiving hydroxyurea at the time of sampling. The results, published in the Journal of Cellular and Molecular Medicine, showed significantly higher levels of all MV types in SCD patients compared with healthy controls.

Patients with LDH levels above 500 IU/L — an indicator of increased hemolysis — had higher RMVs and AMVs. Levels of RMVs also correlated with overall clinical severity, which accounted for vaso-occlusive crises, acute chest syndrome, splenic sequestration and stroke. Conversely, individuals with higher fetal hemoglobin exhibited milder disease. Age, sex and hydroxyurea use did not impact MV levels.

These findings indicate that measuring MVs, particularly RMVs and EMVs, may help clinicians assess hemolysis and vascular injury in SCD. The researchers suggest that prospective studies are needed to determine whether MV measurements could support treatment decisions or serve as prognostic biomarkers.

“In SCD, MVs have been identified as important mediators of vascular complications. Their increased levels correlate with vaso-occlusive crisis (VOCs) frequency, endothelial activation, and enhanced erythrocyte adhesion, amplifying inflammation and vaso‐occlusion,” concluded the authors.

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