# Circulating Erythrocyte‐ and Endothelial‐Derived Microvesicles as Biomarkers of Hemolysis and Clinical Severity in Sickle Cell Disease

## TL;DR

This study explores microvesicles as potential biomarkers for diagnosing and predicting complications in sickle cell disease.

## Contribution

The study identifies erythrocyte- and endothelial-derived microvesicles as novel biomarkers for hemolysis and clinical severity in sickle cell disease.

## Key findings

- SCD patients had significantly higher levels of microvesicles compared to healthy controls.
- Red cell-derived and phosphatidylserine-positive microvesicles correlated with elevated LDH and clinical severity.
- Higher fetal hemoglobin levels were linked to lower endothelial microvesicles, indicating a protective effect.

## Abstract

Sickle cell disease (SCD) is a monogenic disorder caused by the presence of hemoglobin S (Hb S) and is associated with a wide range of clinical complications, including hemolytic anemia, vaso‐occlusive crises (VOC), and acute chest syndrome (ACS). This variability is largely driven by Hb S polymerisation and abnormal cell adhesion, which promote the release of circulating microvesicles (MVs). MVs are small vesicles (0.1–1.0 μm) released from various cell types in response to oxidative stress, cellular activation, or apoptosis. They possess pro‐coagulant and pro‐inflammatory properties and are increasingly recognised as potential modulators of disease processes. In this study, homozygous SCD patients and healthy controls were recruited to characterise their MVs profiles using flow cytometry and to explore associations with clinical and biological parameters. SCD patients exhibited significantly elevated levels of MVs compared to controls. Notably, red cell–derived MVs (RMVs) and phosphatidylserine‐positive MVs (AMVs) were strongly associated with elevated lactate dehydrogenase (LDH) levels and clinical severity. A negative correlation was observed between fetal hemoglobin (Hb F) and endothelial MVs (EMVs), suggesting a protective role of Hb F against endothelial injury. These findings support the potential of MVs as diagnostic and prognostic biomarkers for identifying SCD patients at higher risk of complications.