Mechanics of diseased red blood cells in human spleen and consequences for hereditary blood disorders

He, Liyun; Lu, Lu; Li, Xuejin; Buffet, Pierre; Dao, Ming; Karniadakis, George Em; Suresh, S.

doi:10.1073/pnas.1806501115

Cited by 113 publications

(74 citation statements)

References 40 publications

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“…It is noted that we did not include other blood cells such as red blood cells in our simulations and thus we cannot consider their interaction with platelets, which could affect platelet transport, particularly in the lumen of the MAs. A more detailed model with explicit representations of the red blood cells and platelets, such as [57][58][59][60][61][62], could be used to explore this effect. See our ongoing work to address this problem in electronic supplementary material, figure S3.…”

Section: Discussionmentioning

confidence: 99%

Predictive modelling of thrombus formation in diabetic retinal microaneurysms

Sampani

Zheng

et al. 2020

R. Soc. open sci.

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Microaneurysms (MAs) are one of the earliest clinically visible signs of diabetic retinopathy (DR). Vision can be reduced at any stage of DR by MAs, which may enlarge, rupture and leak fluid into the neural retina. Recent advances in ophthalmic imaging techniques enable reconstruction of the geometries of MAs and quantification of the corresponding haemodynamic metrics, such as shear rate and wall shear stress, but there is lack of computational models that can predict thrombus formation in individual MAs. In this study, we couple a particle model to a continuum model to simulate the platelet aggregation in MAs with different shapes. Our simulation results show that under a physiologically relevant blood flow rate, thrombosis is more pronounced in saccular-shaped MAs than fusiform-shaped MAs, in agreement with recent clinical findings. Our model predictions of the size and shape of the thrombi in MAs are consistent with experimental observations, suggesting that our model is capable of predicting the formation of thrombus for newly detected MAs. This is the first quantitative study of thrombosis in MAs through simulating platelet aggregation, and our results suggest that computational models can be used to predict initiation and development of intraluminal thrombus in MAs as well as provide insights into their role in the pathophysiology of DR.

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Section: Discussionmentioning

confidence: 99%

Predictive modelling of thrombus formation in diabetic retinal microaneurysms

Sampani

Zheng

et al. 2020

R. Soc. open sci.

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“…One of the most distinct properties of a red blood cell (RBC) is the significant elasticity of its membrane. Due to this elasticity, a cell which has a biconcave discoid shape with diameter ∼8 μm and thickness ∼2 μm can pass through capillaries with diameter 3‐5 μm or even smaller test‐of‐fitness slits in the spleen …”

Section: Introductionmentioning

confidence: 99%

Spring‐network model of red blood cell: From membrane mechanics to validation

Jančigová

Kovalčíková

Bohiniková

et al. 2020

Numerical Methods in Fluids

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Summary Red blood cell membrane is highly elastic and proper modeling of this elasticity is essential for biomedical applications that involve computational experiments with blood flow. Inseparable and often some of the most difficult parts of modeling process are verification and validation. In this work, we present a revised model, which uses a spring network to represent the cell membrane immersed in a fluid and has been successfully used in blood flow simulations. We demonstrate the validation steps by first deriving the theoretical relations between the bulk properties of elastic membranes—shear modulus and area compressibility modulus—and parameters of the model that enter the nonlinear stretching and local area conservation computational moduli. We verify the theoretically derived relations using computer simulations of deformable triangular mesh. We calibrate the model by performing a computational version of the optical tweezers experiment. And finally, we validate the modeled cell behavior by investigating the cell rotation frequency when it is subjected to shear flow and cell deformation in narrow channels. The supplementary material contains an extensive dataset that can be used for setting different elastic properties for each cell in simulations of dense suspensions, while still conforming to the biological data. This work contains a complete model development process: From modelling of basic mechanical concepts (the spring network) and advanced biomechanical concepts (such as elasticity of the membrane), through calibration process towards the final stage of model validation.

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“…The spleen contributes to anemia by removing the damaged erythrocytes. Hereditary spherocytosis is spectrin-deficient and ankyrin-deficient erythrocytes dependent and could cause hemolysis [122]. Glycogen storage disease could affect erythrocytes.…”

Section: Anemia As a Major Sign Of Erythrocyte Deformationmentioning

confidence: 99%

Effects of Therapeutic and Toxic Agents on Erythrocytes of Different Species of Animals

Saganuwan¹

2019

Erythrocyte

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A preponderance of therapeutic and toxic agents that affect erythrocytes is being used in preclinical and clinical settings. Such agents are responsible for wrong diagnosis of a myriad of diseases and poor prognosis of some therapeutic interventions. In view of this, literature search was carried out with a view to investigate morphometry of erythrocytes in various diseased conditions and species of animals. Findings have shown that erythrocyte size, area, and volume vary in different species of animals under different diseased conditions. Environmental factors, toxicants, toxins, therapeutics, and management system, among others, can cause erythrocyte deformation, leading to anemia. Erythrocyte-related diseases include but not limited to sickle cell anemia, malaria, cancer, psychiatric illness, and chronic inflammation. Hence the principal source of our survival is erythrocyte, because it transports oxygen needed for metabolism of cell nutrients. erythrocytes (4.2-6.2 Â 10 12 /L), hemoglobin (100 g/100 mL), and hematocrit (38-54%) of the total blood volume are the standards for human species [12]. Variation in species, age, environmental factors, management system, and pathological conditions could affect the size, shape, area, and volume of erythrocytes. MethodologyExtensive literature search was carried out to identify differences between normal and abnormal erythrocytes of various species of animals including the ones in the wild. Information on beneficial and toxic effects of drugs, chemical toxicants, toxins, plant extracts, chemicals, and diseased conditions were searched on erythrocyte shape, size, and volume for various species of animals including human. Some developed formulas were modified for determination of anemic, polycythemic, hydrated, and dehydrated erythrocytes. Physiological and pathological features of the erythrocytes were also highlighted. Preclinical and clinical values of the changes in erythrocytes in relation to blood diseases caused by various agents were critically analyzed. Effects of toxic and therapeutic agents on metabolic, cancer, infectious, inheritable, and noninheritable diseases of erythrocytes, such as sickle cell anemia, malaria, and hereditary spherocytosis, among others, were elucidated. Erythrocyte

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Mechanics of diseased red blood cells in human spleen and consequences for hereditary blood disorders

Cited by 113 publications

References 40 publications

Predictive modelling of thrombus formation in diabetic retinal microaneurysms

Predictive modelling of thrombus formation in diabetic retinal microaneurysms

Spring‐network model of red blood cell: From membrane mechanics to validation

Effects of Therapeutic and Toxic Agents on Erythrocytes of Different Species of Animals

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