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

2019 ◽  
Author(s):  
Emel Islamzada ◽  
Kerryn Matthews ◽  
Quan Guo ◽  
Aline T. Santoso ◽  
Simon P. Duffy ◽  
...  

AbstractA fundamental challenge in the transfusion of red blood cells (RBCs) is that a subset of donated RBC units may not provide optimal benefit to transfusion recipients. This variability stems from the inherent ability of donor RBCs to withstand the physical and chemical insults of cold storage, which ultimately dictate their survival in circulation. The loss of RBC deformability during cold storage is well-established and has been identified as a potential biomarker for the quality of donated RBCs. While RBC deformability has traditionally been indirectly inferred from rheological characteristics of the bulk suspension, there has been considerable interest in directly measuring the deformation of RBCs. Microfluidic technologies have enabled single cell measurement of RBC deformation but have not been able to consistently distinguish differences between RBCs between healthy donors. Using the microfluidic ratchet mechanism, we developed a method to sensitively and consistently analyze RBC deformability. We found that the aging curve of RBC deformability varies significantly across donors, but is consistent for each donor over multiple donations. Specifically, certain donors seem capable of providing RBCs that maintain their deformability during two weeks of cold storage in standard test tubes. The ability to distinguish between RBC units with different storage potential could provide a valuable opportunity to identify donors capable of providing RBCs that maintain their integrity, in order to reserve these units for sensitive transfusion recipients.

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 3694-3694
Author(s):  
Emel Islamzada ◽  
Kerryn Matthews ◽  
Quan Guo ◽  
Aline Santoso ◽  
Mark D. Scott ◽  
...  

A fundamental challenge in the transfusion of red blood cells (RBCs) is that not all donated RBC units will confer the same benefit to the recipient. While some RBC units will remain in circulation for long periods after transfusion maintaining homeostasis, some will be cleared rapidly, leading to the need of an increased number of transfusions. This variability stems, in part, from the inherent ability of donor RBCs to withstand the physical and chemical insults of cold storage, which ultimately dictate their survival in circulation. The loss of RBC deformability during cold storage is well-established and has been identified as a potential biomarker for the quality of donated RBCs. Previous methods for characterizing RBC deformability have been limited in their sensitivity and consistency. As a result, these methods have only been able to characterize pathological and chemically degraded RBCs, but have not been able to distinguish differences between healthy donors. Recently, we developed a microfluidic device to sort RBCs based on deformability using a matrix of asymmetrical tapered constrictions that form microfluidic ratchets. Due to the geometric asymmetry of the taper, the force required to deform cells through the constriction along the direction of taper is less than against the direction of taper. Coupling this deformation asymmetry with an oscillatory flow creates a ratcheting effect that selectively transports cells based on their ability to squeeze through each microscopic constriction. Importantly, this oscillatory flow also minimizes the contact between cells and the filter microstructure to prevent clogging and fouling to ensure that a consistent filtration force is applied to each cell. We measured the deformability profiles of eight healthy donors using the microfluidic ratchet device. We found the deformability profile to be consistent for each donor over multiple donations. We also found significant variability across different donors. We then cold stored donated RBCs in SAGM media in plastic test tubes for 14 days to accelerate cold storage related damage. We find that the aging curve of RBC deformability varies significantly across donors, but is also consistent for each donor over multiple donations. Specifically, certain donors seem capable of providing RBCs that maintain their deformability during two weeks of accelerated aging. This study illustrates a potential route to identify high-quality donors, or super-donors, that can provide RBCs that maintain their integrity during cold storage. Being able to identify these donors will enable blood bankers to reserve high-quality RBC units for chronic transfusion recipients, which will reduce the total number of transfusions for these patients and increase the overall blood supply. Disclosures Ma: Patent (US 9880084): Other: Inventor.


2005 ◽  
Vol 11 (S03) ◽  
pp. 66-69
Author(s):  
E. F. Costa ◽  
S. M. M. Magalhaes ◽  
M. S. Pitombeira ◽  
J. A. K. Freire ◽  
V. N. Freire ◽  
...  

Atomic Force Microscopy (AFM) is a recent technique that allows evaluation of features in biological systems that could not be previously observed by other instruments. Red Blood Cells (RBC) have been extensively studied because of their relatively simple membrane structure, convenience of preparation and scanning [1]. As an ancillary way of confirming diagnoses, AFM has mostly been used to determine shape and size of RBCs, which are important indicators of some blood diseases or disordered erythropoiesis [2]. In Myelodysplastic Syndrome (MDS) hematopoiesis is inefficacious with consequent anemia that may evolve to acute leukemia. Genomic alterations lead to structural defects in the biomolecular network that forms the erythrocyte membrane. The deformation capability of the cells and their lifetime in circulation are diminished [5]. AFM allows us to observe in a controlled way the response of these membrane molecular networks under physical and chemical stimuli in many different physiological conditions, such as in air and liquids [6]. Using this technique, many new characteristics have been found in erythrocyte membranes that are still of undetermined significance [3,4]. The aim of our work is to compare membrane morphology of two groups of blood donors, that is, healthy subjects and patients with MDS. The images yielded by AFM confirm the structure of the erythrocytes and reveal interesting submicron features on the cell, suggesting a way to distinguish between RBCs from healthy donors and RBCs from patients with MDS.


2021 ◽  
Author(s):  
Emel Islamzada ◽  
Kerryn Matthews ◽  
Erik Lamoureux ◽  
Simon P Duffy ◽  
Mark D Scott ◽  
...  

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.


Transfusion ◽  
2017 ◽  
Vol 58 (2) ◽  
pp. 423-429 ◽  
Author(s):  
Athinoula Meli ◽  
Vicky Hancock ◽  
Heidi Doughty ◽  
Steve Smedley ◽  
Rebecca Cardigan ◽  
...  

Lab on a Chip ◽  
2020 ◽  
Vol 20 (2) ◽  
pp. 226-235 ◽  
Author(s):  
Emel Islamzada ◽  
Kerryn Matthews ◽  
Quan Guo ◽  
Aline T. Santoso ◽  
Simon P. Duffy ◽  
...  

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.


2014 ◽  
Vol 2014 ◽  
pp. 1-5 ◽  
Author(s):  
I. M. Lamzin ◽  
R. M. Khayrullin

At the moment the suitability of stored red blood cells (sRBC) for transfusion is checked by routine methods such as haemoglobin estimation and the level of haemolysis. These methods cannot characterize directly the quality of the membranes of sRBC. The aim of this work is to assess the quality of sRBC based on such criteria as the membrane’s stiffness and the size and the form of sRBC. Materials and Methods. We have investigated 5 series of dry cytosmears of the sRBC which had been kept in blood bank in a period from 1 to 35 days. After AFM imaging, in every specimen, 5 RBC were chosen at random; the diameter, the height, and the stiffness were measured on each of them. Results. The present study shows high increase of the mean values of YM and height of RBC after 35 days of storage and decrease of the mean values of their diameter. Conclusion. Statistically significant high increase of the mean values of YM indicates the decrease of the elasticity of the cells in the course of storing of the RBC. This parameter along with the morphological characteristics can be used as criterion for assessment of applicability of the sRBC for blood transfusion.


2017 ◽  
Vol 61 (No. 8) ◽  
pp. 443-448 ◽  
Author(s):  
DA Bala ◽  
E. Eraslan ◽  
I. Akyazi ◽  
EE Ekiz ◽  
M. Ozcan ◽  
...  

Studies on the frozen storage of human blood products have benefited veterinary transfusion medicine in recent years, but the long-term cryopreservation of canine red blood cells (RBCs) has not yet been thoroughly investigated. Further, no studies are available with respect to the frozen storage of leukocyte-depleted canine red blood cells (LD-RBCs). The objective of the current study was to investigate time-dependent effects of long-term frozen storage on leukocyte-depleted canine RBCs. Twelve healthy adult dogs meeting the criteria for blood transfusion were used in the study. Whole blood samples (450 ± 45 ml) collected from each dog were centrifuged for 5 min at 22 °C and 4200 × g in a cryogenic microcentrifuge and concentrated RBC (pRBC) suspensions were obtained. Leukocyte depletion was achieved by filtration (2.6 log<sub>10</sub>). Then, the filtrated samples were prewashed three times in 0.9% NaCl solution and were allocated into three subgroups to be evaluated at three different time points (Day 0, Month 4 and Month 6). The samples for cryopreservation were subjected to glycerolisation and then stored at –80 °C for 4- and 6-month periods. At the end of this period pRBC units were thawed by manual agitation in a water bath maintained at 36–38 °C, centrifuged and then washed in a consecutive series of 12%, 1.6% and 0.9% of NaCl + 0.2 dextrose solutions. 2,3-Diphosphoglycerate (2,3-DPG), adenosine triphosphate (ATP), supernatant haemoglobin (SupHb), sodium (Na<sup>+</sup>) and potassium (K<sup>+</sup>) levels, residual glycerol concentrations and haemograms of thawed and deglycerolised pRBC samples were evaluated together with those of Day 0. Sterility tests were performed on all samples for bacterial contamination. No statistically significant differences were noted except for Hct and SupHb levels. No bacterial contamination was noted in any of the samples on the basis of sterility tests. It was found that the described glycerolisation procedure could be a method of choice in the cryopreservation of leukocyte-depleted pRBCs (LD-pRBCs) since no negative effect was observed on the quality of the products and long-term frozen storage did not cause RBC destruction.


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