Deformability of transfused red blood cells is a potent effector of transfusion‐induced hemoglobin increment: A study with β‐thalassemia major patients

Barshtein, Gregory; Goldschmidt, Neta; Pries, Axel R.; Zelig, Orly; Arbell, Dan; Yedgar, Saul

doi:10.1002/ajh.24821

Cited by 29 publications

(48 citation statements)

References 4 publications

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“…As we have recently shown, RBC deformability exerts a direct effect on transfusion outcome as an independent factor. 2,5 At any storage duration, RBC deformability is the result of its initial state, the blood banking procedure applied to the unit and the effect of storage duration. Therefore, the FIFO criterion is not sufficient for assessing the potential transfusion outcome, and the RBC haemodynamic functionality should be specifically determined for each unit of packed RBC, independent of the storage duration.…”

Section: Discussionmentioning

confidence: 99%

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Inter‐donor variability in deformability of red blood cells in blood units

Barshtein

Rasmusen

Zelig

et al. 2020

Transfusion Medicine

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Objective: This study aimed to examine the donor-to-donor variability in the deformability of red blood cells (RBCs) from freshly collected blood donations (F-RBC) and packed RBCs. Background: Packed RBCs are supplied for transfusion by the first-in-first-out (FIFO) criterion, assuming that their quality is the same for packed RBCs with equal storage duration. To challenge this notion, we determined the deformability of F-RBC and packed RBCs stored for different durations. Methods: Three RBC groups were employed: A. 79 samples of F-RBC; B. 76 samples of packed RBC units, randomly used for transfusion at different storage durations; and C. 65 samples of outdated packed RBCs stored for 35 to 37 days. All packed RBC units were non-leukofiltrated and stored in Citrate-phosphate-dextrose solution with adenine (CPDA-1). RBC deformability was determined using a computerised cell-flow properties analyser, which monitors the shape change of cells directly visualised in a narrow-gap flow chamber and provides the cells' deformability distribution in a large RBC population. Results: The F-RBC deformability exhibited a wide-range inter-donor variability. The cold storage of packed RBCs exerted a mild reduction of deformability, which became significant, compared to the initial inter-donor variability, only after 3 weeks of storage. Conclusion: Packed RBCs are generally supplied for transfusion by the FIFO criterion based on the assumption that the storage duration is a key factor of RBC quality. This study demonstrates that the deformability of red blood cells is significantly different in donors, and substantial variability persists throughout the entire process of their storage. Therefore, the FIFO criterion is not sufficient for assessing the RBC deformability, which should, therefore, be specifically characterised for each unit.

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Section: Discussionmentioning

confidence: 99%

“…addition to the median elongation ratio (MER). 2,5 Of particular interest is the fraction of low deformable cells (%LDFC, ER ≤1.4), which better express the capacity of transfused RBCs to impair blood circulation. 5 ).…”

Section: Methodsmentioning

confidence: 99%

Inter‐donor variability in deformability of red blood cells in blood units

Barshtein

Rasmusen

Zelig

et al. 2020

Transfusion Medicine

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“…A recent study in patients with thalassemia showed that the increase in hemoglobin following transfusion was inversely correlated to the proportion of “less deformable” RBC in the RCC ( 57 ). In this study, a cell flow analyzer ( 69 ) was used to measure the elongation index of individual RBC that adheres to a polystyrene slide.…”

Section: Storage Lesion Transfusion Recovery and Spleen Filtrationmentioning

confidence: 99%

Measuring Post-transfusion Recovery and Survival of Red Blood Cells: Strengths and Weaknesses of Chromium-51 Labeling and Alternative Methods

2018

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The proportion of transfused red blood cells (RBCs) that remain in circulation is an important surrogate marker of transfusion efficacy and contributes to predict the potential benefit of a transfusion process. Over the last 50 years, most of the transfusion recovery data were generated by chromium-51 (51Cr)-labeling studies and were predominantly performed to validate new storage systems and new processes to prepare RBC concentrates. As a consequence, our understanding of transfusion efficacy is strongly dependent on the strengths and weaknesses of 51Cr labeling in particular. Other methods such as antigen mismatch or biotin-based labeling can bring relevant information, for example, on the long-term survival of transfused RBC. These radioactivity-free methods can be used in patients including from vulnerable groups. We provide an overview of the methods used to measure transfusion recovery in humans, compare their strengths and weaknesses, and discuss their potential limitations. Also, based on our understanding of the spleen-specific filtration of damaged RBC and historical transfusion recovery data, we propose that RBC deformability and morphology are storage lesion markers that could become useful predictors of transfusion recovery. Transfusion recovery can and should be accurately explored by more than one method. Technical optimization and clarification of concepts is still needed in this important field of transfusion and physiology.

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“…For example, patients with beta thalassemia major, in which a genetic mutation results in significantly reduced beta‐globin production, also produce RBCs with reduced deformability . This leads to severe anemia and subsequent dependence on RBC transfusions that may alter the patient's hemodynamic environment . Furthermore, in transfusion medicine, physical modification and degradation of RBCs (storage lesion) is known to occur when stored in blood banks due to accumulation of microparticles and alterations in the plasma membrane structure of the stored RBCs .…”

Section: Introductionmentioning

confidence: 99%

Integrated automated particle tracking microfluidic enables high‐throughput cell deformability cytometry for red cell disorders

et al. 2018

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Investigating individual red blood cells (RBCs) is critical to understanding hematologic diseases, as pathology often originates at the single-cell level. Many RBC disorders manifest in altered biophysical properties, such as deformability of RBCs. Due to limitations in current biophysical assays, there exists a need for high-throughput analysis of RBC deformability with single-cell resolution. To that end, we present a method that pairs a simple in vitro artificial microvasculature network system with an innovative MATLAB-based automated particle tracking program, allowing for high-throughput, single-cell deformability index (sDI) measurements of entire RBC populations. We apply our technology to quantify the sDI of RBCs from healthy volunteers, Sickle cell disease (SCD) patients, a transfusion-dependent beta thalassemia major patient, and in stored packed RBCs (pRBCs) that undergo storage lesion over 4 weeks. Moreover, our system can also measure cell size for each RBC, thereby enabling 2D analysis of cell deformability vs cell size with single cell resolution akin to flow cytometry. Our results demonstrate the clear existence of distinct biophysical RBC subpopulations with high interpatient variability in SCD as indicated by large magnitude skewness and kurtosis values of distribution, the "shifting" of sDI vs RBC size curves over transfusion cycles in beta thalassemia, and the appearance of low sDI RBC subpopulations within 4 days of pRBC storage. Overall, our system offers an inexpensive, convenient, and high-throughput method to gauge single RBC deformability and size for any RBC population and has the potential to aid in disease monitoring and transfusion guidelines for various RBC disorders.

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Deformability of transfused red blood cells is a potent effector of transfusion‐induced hemoglobin increment: A study with β‐thalassemia major patients

Cited by 29 publications

References 4 publications

Inter‐donor variability in deformability of red blood cells in blood units

Inter‐donor variability in deformability of red blood cells in blood units

Measuring Post-transfusion Recovery and Survival of Red Blood Cells: Strengths and Weaknesses of Chromium-51 Labeling and Alternative Methods

Integrated automated particle tracking microfluidic enables high‐throughput cell deformability cytometry for red cell disorders

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