The Erythrocyte Sedimentation Rate and Its Relation to Cell Shape and Rigidity of Red Blood Cells from Chorea-Acanthocytosis Patients in an Off-Label Treatment with Dasatinib

Abstract

Background: Chorea-acanthocytosis (ChAc) is a rare hereditary neurodegenerative disease with deformed red blood cells (RBCs), so-called acanthocytes, as a typical marker of the disease. Erythrocyte sedimentation rate (ESR) was recently proposed as a diagnostic biomarker. To date, there is no treatment option for affected patients, but promising therapy candidates, such as dasatinib, a Lyn-kinase inhibitor, have been identified. Methods: RBCs of two ChAc patients during and after dasatinib treatment were characterized by the ESR, clinical hematology parameters and the 3D shape classification in stasis based on an artificial neural network. Furthermore, mathematical modeling was performed to understand the contribution of cell morphology and cell rigidity to the ESR. Microfluidic measurements were used to compare the RBC rigidity between ChAc patients and healthy controls. Results: The mechano-morphological characterization of RBCs from two ChAc patients in an off-label treatment with dasatinib revealed differences in the ESR and the acanthocyte count during and after the treatment period, which could not directly be related to each other. Clinical hematology parameters were in the normal range. Mathematical modeling indicated that RBC rigidity is more important for delayed ESR than cell shape. Microfluidic experiments confirmed a higher rigidity in the normocytes of ChAc patients compared to healthy controls. Conclusions: The results increase our understanding of the role of acanthocytes and their associated properties in the ESR, but the data are too sparse to answer the question of whether the ESR is a suitable biomarker for treatment success, whereas a correlation between hematological and neuronal phenotype is still subject to verification.

Changes in blood cell deformability in Chorea-Acanthocytosis and effects of treatment with dasatinib or lithium

“…The decreased deformability can be directly inferred from the reduced number of deformed cells at any cell velocity. A reduced deformability of ChAc RBCs, deduced from cell shapes, has recently also been reported by Rabe et al, 2021 (39).…”

Imaging Erythrocyte Sedimentation in Whole Blood

“…We show that, for every geometry we probed, erythrocytes form a continuous network with characteristic cracks, i.e., a colloidal gel. These imaging techniques then support the most recent models for erythrocytes sedimentation (Darras et al, 2021b; and supports mechanistic explanation of how deformed erythrocytes influence the ESR (Darras et al, 2021a;Rabe et al, 2021). Furthermore, they open the way for a quantitative analysis of the erythrocyte related processes and interactions during the sedimentation, even though such analysis requires a further refinement of the experimental set-ups.…”

“…Irregular shaped or rigidified cells, like sickle cells (Jan et al, 1981;Lawrence and Fabry, 1986) or acanthocytes (Salt et al, 1960) decrease the ESR. Although there is no lower limit established as a pathological limit, a low ESR was proposed as a biomarker for diseases belonging to the neuroacanthocytosis syndrome (NAS) (Darras et al, 2021a;Rabe et al, 2021). Moreover, the viscosity of the plasma also have an influence on the ESR (Késmárky et al, 2008).…”

Sequential quantification of blood and diluent using red cell sedimentation-based separation and pressure-induced work in a microfluidic channel

“…Higher concentrations of plasma protein, such as fibrinogen, lead to enhance RBC aggregation, 18 erythrocyte sedimentation rate (ESR), and C-reactive protein. 19 Clinically, inflammatory conditions (including diabetes, hypertension, sepsis, stroke, and Alzheimer's disease), 20 neuro-acanthocytosis, 21,22 and microcirculatory disorders elevate RBC aggregation substantially. 23 The ESR method, devised by Westergren a century ago, has been commonly used to detect inflammatory activity.…”