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

Misshaped red blood cells (RBCs), characterized by thorn-like protrusions known as acanthocytes, are a key diagnostic feature in Chorea-Acanthocytosis (ChAc), a rare neurodegenerative disorder. The altered RBC morphology likely influences their biomechanical properties which are crucial for the cells to pass the microvasculature. Here, we investigated blood cell deformability of 5 ChAc patients compared to healthy controls during up to one-year individual off-label treatment with the tyrosine kinases inhibitor dasatinib or several weeks with lithium. Measurements with two microfluidic techniques allowed us to assess RBC deformability under different shear stresses. Furthermore, we characterized leukocyte stiffness at high shear stresses. The results show that blood cell deformability - including both RBCs and leukocytes - in general is altered in ChAc patients compared to healthy donors. Therefore, this study shows for the first time an impairment of leukocyte properties in ChAc. During treatment with dasatinib or lithium, we observe alterations in RBC deformability and a stiffness increase for leukocytes. The hematological phenotype of ChAc patients hints at a reorganization of the cytoskeleton in blood cells which partly explains the altered mechanical properties observed here. These findings highlight the need for a systematic assessment of the contribution of impaired blood cell mechanics to the clinical manifestation of ChAc.

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Susceptibility of density-fractionated erythrocytes to subhaemolytic mechanical shear stress

The International Journal of Artificial Organs ◽

10.1177/0391398818790334 ◽

2018 ◽

Vol 42 (3) ◽

pp. 151-157 ◽

Cited By ~ 4

Author(s):

Antony P McNamee ◽

Kieran Richardson ◽

Jarod Horobin ◽

Lennart Kuck ◽

Michael J Simmonds

Keyword(s):

Blood Cell ◽

Red Blood Cells ◽

Red Blood Cell ◽

Blood Cells ◽

Shear Stresses ◽

Mechanical Stimuli ◽

Cell Deformability ◽

Red Blood Cell Deformability ◽

Cell Age ◽

Low Shear

Introduction: Accumulating evidence demonstrates that subhaemolytic mechanical stresses, typical of circulatory support, induce physical and biochemical changes to red blood cells. It remains unclear, however, whether cell age affects susceptibility to these mechanical forces. This study thus examined the sensitivity of density-fractionated red blood cells to sublethal mechanical stresses. Methods: Red blood cells were isolated and washed twice, with the least and most dense fractions being obtained following centrifugation (1500 g × 5 min). Red blood cell deformability was determined across an osmotic gradient and a range of shear stresses (0.3–50 Pa). Cell deformability was also quantified before and after 300 s exposure to shear stresses known to decrease (64 Pa) or increase (10 Pa) red blood cell deformability. The time course of accumulated sublethal damage that occurred during exposure to 64 Pa was also examined. Results: Dense red blood cells exhibited decreased capacity to deform when compared with less dense cells. Cellular response to mechanical stimuli was similar in trend for all red blood cells, independent of density; however, the magnitude of impairment in cell deformability was exacerbated in dense cells. Moreover, the rate of impairment in cellular deformability, induced by 64 Pa, was more rapid for dense cells. Relative improvement in red blood cell deformability, due to low-shear conditioning (10 Pa), was consistent for both cell populations. Conclusion: Red blood cell populations respond differently to mechanical stimuli: older (more dense) cells are highly susceptible to sublethal mechanical trauma, while cell age (density) does not appear to alter the magnitude of improved cell deformability following low-shear conditioning.

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Assessing Red Blood Cell Deformability using Deep Learning

Lab on a Chip ◽

10.1039/d1lc01006a ◽

2021 ◽

Author(s):

Erik S. Lamoureux ◽

Emel Islamzada ◽

Matthew V.J. Wiens ◽

Kerryn Matthews ◽

Simon P. Duffy ◽

...

Keyword(s):

Deep Learning ◽

Blood Cell ◽

Red Blood Cells ◽

Red Blood Cell ◽

Blood Cells ◽

Natural Aging ◽

Cell Deformability ◽

Red Blood Cell Deformability ◽

Rbc Deformability

Red blood cells (RBCs) must be highly deformable to transit through the microvasculature to deliver oxygen to tissues. The loss of RBC deformability resulting from pathology, natural aging, or storage...

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Degradation of Red Blood Cell Deformability during Cold Storage in Blood Bags

10.1101/2021.07.20.452409 ◽

2021 ◽

Author(s):

Emel Islamzada ◽

Kerryn Matthews ◽

Erik Lamoureux ◽

Simon P Duffy ◽

Mark D Scott ◽

...

Keyword(s):

Blood Cell ◽

Red Blood Cells ◽

Cold Storage ◽

Blood Cells ◽

Current Standard ◽

High Quality ◽

Cell Deformability ◽

Storage Lesion ◽

Progressive Loss ◽

Rbc Deformability

Red blood cells (RBCs) stored in blood bags develop a storage lesion that include structural, metabolic, and morphologic transformations resulting in a progressive loss of RBC deformability. The speed of RBC deformability loss is donor-dependent, which if properly characterized, could be used as a biomarker to select high-quality RBC units for sensitive recipients or to provide customized storage timelines depending on the donor. We used the microfluidic ratchet device to measure the deformability of red blood cells stored in blood bags every 14 days over a span of 56 days. We observed that storage in blood bags generally prevented RBC deformability loss over the current standard 42-day storage window. However, between 42 and 56 days, the deformability loss profile varied dramatically between donors. In particular, we observed accelerated RBC deformability loss for a majority of male donors, but for none of the female donors. Together, our results suggest that RBC deformability loss could be used to screen for donors who can provide stable RBCs for sensitive transfusion recipients or to identify donors capable of providing RBCs that could be stored for longer than the current 42-day expiration window.

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In vitro effects of temperature on red blood cell deformability and membrane stability in human and various vertebrate species

Clinical Hemorheology and Microcirculation ◽

10.3233/ch-211118 ◽

2021 ◽

pp. 1-10

Author(s):

Adam Attila Matrai ◽

Gabor Varga ◽

Bence Tanczos ◽

Barbara Barath ◽

Adam Varga ◽

...

Keyword(s):

Blood Cell ◽

Red Blood Cell ◽

Whole Blood ◽

Mechanical Stability ◽

Cell Deformability ◽

Blood Samples ◽

Effects Of Temperature ◽

The Way ◽

Rbc Deformability

BACKGROUND: The effects of temperature on micro-rheological variables have not been completely revealed yet. OBJECTIVE: To investigate micro-rheological effects of heat treatment in human, rat, dog, and porcine blood samples. METHODS: Red blood cell (RBC) - buffer suspensions were prepared and immersed in a 37, 40, and 43°C heat-controlled water bath for 10 minutes. Deformability, as well as mechanical stability of RBCs were measured in ektacytometer. These tests were also examined in whole blood samples at various temperatures, gradually between 37 and 45°C in the ektacytometer. RESULTS: RBC deformability significantly worsened in the samples treated at 40 and 43°C degrees, more expressed in human, porcine, rat, and in smaller degree in canine samples. The way of heating (incubation vs. ektacytometer temperation) and the composition of the sample (RBC-PBS suspension or whole blood) resulted in the different magnitude of RBC deformability deterioration. Heating affected RBC membrane (mechanical) stability, showing controversial alterations. CONCLUSION: Significant changes occur in RBC deformability by increasing temperature, showing inter-species differences. The magnitude of alterations is depending on the way of heating and the composition of the sample. The results may contribute to better understanding the micro-rheological deterioration in hyperthermia or fever.

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A physiometer for simultaneous measurement of whole blood viscosity and its determinants: hematocrit and red blood cell deformability

The Analyst ◽

10.1039/c8an02135j ◽

2019 ◽

Vol 144 (9) ◽

pp. 3144-3157 ◽

Cited By ~ 9

Author(s):

Byung Jun Kim ◽

Ye Sung Lee ◽

Alexander Zhbanov ◽

Sung Yang

Keyword(s):

Blood Cell ◽

Red Blood Cell ◽

Blood Viscosity ◽

Simultaneous Measurement ◽

Whole Blood ◽

Cell Deformability ◽

Whole Blood Viscosity ◽

Red Blood Cell Deformability ◽

Rbc Deformability

In this study, a microfluidic-based physiometer capable of measuring the whole blood viscosity, hematocrit, and red blood cell (RBC) deformability on a chip is introduced.

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Deformability based sorting of stored red blood cells reveals donor-dependent aging curves

Lab on a Chip ◽

10.1039/c9lc01058k ◽

2020 ◽

Vol 20 (2) ◽

pp. 226-235 ◽

Cited By ~ 6

Author(s):

Emel Islamzada ◽

Kerryn Matthews ◽

Quan Guo ◽

Aline T. Santoso ◽

Simon P. Duffy ◽

...

Keyword(s):

Blood Cell ◽

Red Blood Cells ◽

Cold Storage ◽

Red Blood Cell ◽

Cell Sorting ◽

Blood Cells ◽

Cell Deformability ◽

Red Blood Cell Deformability

Cell sorting using microfluidic ratchets enables sensitive and consistent characterization of donor red blood cell deformability. Using this capability, we show the degradation of red blood cell deformability during cold storage is donor-dependent.

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Regulation of red blood cell filterability by Ca2+ influx and cAMP-mediated signaling pathways

AJP Cell Physiology ◽

10.1152/ajpcell.1997.273.6.c1828 ◽

1997 ◽

Vol 273 (6) ◽

pp. C1828-C1834 ◽

Cited By ~ 64

Author(s):

Tadahiro Oonishi ◽

Kanako Sakashita ◽

Nobuhiro Uyesaka

Keyword(s):

Blood Cell ◽

Red Blood Cells ◽

Signaling Pathways ◽

Mechanical Stress ◽

Red Blood Cell ◽

Blood Cells ◽

Camp Level ◽

Membrane Properties ◽

Cell Deformability ◽

Red Blood Cell Deformability

To investigate the mechanism of the regulation of human red blood cell deformability, we examined the deformability under mechanical stress. Washed human red blood cells were rapidly injected through a fine needle, and their filterability was measured using a nickel mesh filter. The decrease in filterability showed a V-shaped curve depending on the extracellular Ca2+ concentration; the maximum decrease was achieved at ∼50 μM. The decreased filterability was accompanied by no change in cell morphology and cell volume, indicating that the decrease in filterability can be ascribed to alterations of the membrane properties. Ca2+entry blockers (nifedipine and felodipine) inhibited the impairment of filterability under mechanical stress. Prostaglandins E1 and E2, epinephrine, and pentoxifylline, which are thought to modulate the intracellular adenosine 3′,5′-cyclic monophosphate (cAMP) level of red blood cells, improved or worsened the impaired filterability according to their expected actions on the cAMP level of the cells. These results strongly suggest that the membrane properties regulating red blood cell deformability are affected by the signal transduction system, including Ca2+-dependent and cAMP-mediated signaling pathways.

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Red blood cell deformability and protein adsorption on red blood cell surface

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.1984.247.5.h739 ◽

1984 ◽

Vol 247 (5) ◽

pp. H739-H747

Author(s):

Y. Kikuchi ◽

T. Koyama

Keyword(s):

Ionic Strength ◽

Blood Cell ◽

Protein Adsorption ◽

Plasma Protein ◽

Protein Interaction ◽

Red Blood Cell ◽

Dominant Role ◽

Cell Protein ◽

Cell Deformability ◽

Rbc Deformability

Effects of protein and NaCl concentrations in plasma on red blood cell (RBC) deformability were studied using fresh human blood and a 5-microns Nuclepore filtration test. The protein and salt concentrations were varied by diluting the plasma with saline and adding crystalline NaCl to the fluids, respectively. The mean pore passage time of the RBCs, which was measured as an index of the deformability, increased with increasing plasma protein and NaCl concentrations. A marked interdependence was observed; the relation of RBC deformability with plasma protein was accentuated by an increase in plasma NaCl, whereas the effect of increasing plasma NaCl was diminished by a decrease in plasma protein. It is suggested that the RBC-protein interaction which is modified by the fluid ionic strength plays a dominant role in producing these characteristic changes in RBC deformability with protein and salt contents in the plasma. An analysis is made of the cell-protein interaction; the electric repulsive and van der Waals attractive forces are calculated with a result that the protein adsorption on a RBC increases with increasing fluid ionic strength above normal. This analysis, furthermore, provides information on the surface charge distribution on a RBC.

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Effects of nitric oxide on red blood cell deformability

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.00665.2002 ◽

2003 ◽

Vol 284 (5) ◽

pp. H1577-H1584 ◽

Cited By ~ 163

Author(s):

Melek Bor-Kucukatay ◽

Rosalinda B. Wenby ◽

Herbert J. Meiselman ◽

Oguz K. Baskurt

Keyword(s):

Nitric Oxide ◽

Blood Cell ◽

Guanylate Cyclase ◽

Red Blood Cell ◽

Soluble Guanylate Cyclase ◽

Shear Stresses ◽

No Donors ◽

Nos Inhibitors ◽

Deta Nonoate ◽

Rbc Deformability

In addition to its known action on vascular smooth muscle, nitric oxide (NO) has been suggested to have cardiovascular effects via regulation of red blood cell (RBC) deformability. The present study was designed to further explore this possibility. Human RBCs in autologous plasma were incubated for 1 h with NO synthase (NOS) inhibitors [ N ω-nitro-l-arginine methyl ester (l-NAME) and S-methylisothiourea], NO donors [sodium nitroprusside (SNP) and diethylenetriamine (DETA)-NONOate], an NO precursor (l-arginine), soluble guanylate cyclase inhibitors (1H-[1,2,4]oxadiazolo-[4,3-a]quinoxalin-1-one and methylene blue), and a potassium channel blocker [triethylammonium (TEA)]. After incubation, RBC deformability at various shear stresses was determined by ektacytometry. Both NOS inhibitors significantly reduced RBC deformability above a threshold concentration, whereas the NO donors increased deformability at optimal concentrations. NO donors, as well as the NO precursor l-arginine and the potassium blocker TEA, were able to reverse the effects of NOS inhibitors. Guanylate cyclase inhibition reduced RBC deformation, with both SNP and DETA-NONOate able to reverse this effect. These results thus indicate the importance of NO as a determinant of RBC mechanical behavior and suggest its regulatory role for normal RBC deformability.

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