A novel red blood cell deformability biomarker is associated with hemolysis and vaso-occlusive crises in sickle cell disease.

Sickle cell disease (SCD) is among the most prevalent genetic disorders worldwide. It is characterized by unpredictable and potentially fatal vaso-occlusive crises, directly linked to the stiffening of red blood cells (RBCs) due to the formation of hemoglobin fibers in their cytoplasm. Here, we propose a new mechanical marker: the proportion of RBCs in a blood sample deformable enough to exhibit a specific tank-treading motion, in shear flow at a given shear rate. This marker is significantly lower in SCD patients than in controls and is sensitive to RBC density and dehydration, two factors that influence hemoglobin polymerization in SCD. The marker was tested in a cohort of 21 SCD patients, with weekly monitoring conducted over a period of 6 months. It correlates with key biological parameters of SCD including fetal hemoglobin levels, reticulocyte count, serum LDH levels, and the use of antihypertensive treatments. The marker significantly decreases before vaso-occlusive crises requiring hospitalization. These findings indicate that this marker may act as a comprehensive indicator of RBC deformability, offering valuable insights for the continuous clinical monitoring of SCD patients. It could play a role in managing or preventing vaso-occlusive crises and holds potential for the development of new diagnostic tests such as point-of-care or companion diagnostic devices for personalized medicine.