Abstract 3680: Transfusion-Induced Tissue Hypoxia is Ameliorated by
            S
            -nitrosohemoglobin Repletion of Stored Red Blood Cells

Transfusion of stored red blood cells (RBCs) is associated with a decrease in tissue oxygenation in animal models and with increased mortality and morbidity in patients. Recent studies have demonstrated that stored RBCs are deficient in vasodilatory ability and depleted of S -nitrosohemoglobin (SNO-Hb), and that renitrosylation ex vivo can increase SNO-Hb levels and restore vasoactivity. We have examined in a mouse model the extent to which transfusion impairs tissue oxygenation and whether SNO-Hb repletion can ameliorate that impairment. We report here that transfusion of (mouse) RBCs stored for 1 day or 1 week results in tissue hypoxia that is largely prevented by SNO-Hb repletion prior to transfusion ( 1 day stored blood : % decrease in oxygenation 58+/−10% untreated vs. 92+/−0.7% SNO-Hb repleted, p<0.05, n=3– 6; 1 week stored blood : % decrease in oxygenation 66+/−10% untreated vs. 91+/−2.8% SNO-Hb repleted, p<0.05, n=3– 6). Storage of mouse blood beyond human expiration-equivalents (1 month) resulted in substantial lysis and the death of all mice transfused (native and SNO-Hb repleted blood, n=5). In conclusion, repletion of SNO-Hb ameliorates the decrease in tissue oxygenation that results from transfusion of untreated stored blood. Therefore, SNO-Hb repletion may provide a simple and efficacious method to reduce transfusion-related mortality and morbidity.

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Hemoglobin Oxidation in Stored Blood Accelerates Hemolysis and Oxidative Injury to Red Blood Cells

Journal of Laboratory Physicians ◽

10.1055/s-0040-1721156 ◽

2020 ◽

Vol 12 (04) ◽

pp. 244-249

Author(s):

Ibrahim Mustafa ◽

Tameem Ali Qaid Hadwan

Keyword(s):

Red Blood Cells ◽

Blood Cells ◽

Morphological Changes ◽

Hemoglobin Concentration ◽

Red Cell Membrane ◽

Rbc Membrane ◽

Hemoglobin Oxidation ◽

Rbc Indices ◽

Methemoglobin Formation ◽

Stored Blood

Abstract Introduction Maintaining blood supply is a challenge in blood banks. Red blood cells (RBCs) stored at 4°C experience issues of biochemical changes due to metabolism of cells, leading to changes collectively referred to as “storage lesions.” Oxidation of the red cell membrane, leading to lysis, contributes to these storage lesions. Methods Blood bags with CPD-SAGM stored at 4°C for 28 days were withdrawn aseptically on days 1, 14, and 28. Hematology analyzer was used to investigate RBC indices. Hemoglobin oxidation was studied through spectrophotometric scan of spectral change. RBC lysis was studied with the help of Drabkin's assay, and morphological changes were observed by light and scan electron microscopy. Results RBCs show progressive changes in morphology echinocytes and spherocytes on day 28. There was 0.85% RBC lysis, an approximately 20% decrease in percentage oxyhemoglobin, and a 14% increase in methemoglobin formation, which shows hemoglobin oxidation on day 28. Conclusions Oxidative damage to RBC, with an increase in storage time was observed in the present study. The observed morphological changes to RBC during the course of increased time shows that there is progressive damage to RBC membrane and a decrease in hemoglobin concentration; percentage RBC lysis is probably due to free hemoglobin and iron.

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Pharmacologic Targeting of Red Blood Cells to Improve Tissue Oxygenation

Clinical Pharmacology & Therapeutics ◽

10.1002/cpt.979 ◽

2018 ◽

Vol 104 (3) ◽

pp. 553-563 ◽

Cited By ~ 5

Author(s):

James D. Reynolds ◽

Trevor Jenkins ◽

Faisal Matto ◽

Ryan Nazemian ◽

Obada Farhan ◽

...

Keyword(s):

Red Blood Cells ◽

Blood Cells ◽

Tissue Oxygenation

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More efficient exchange of sickle red blood cells can be achieved by exchanging the densest red blood cells: An ex vivo proof of concept study

Transfusion and Apheresis Science ◽

10.1016/j.transci.2018.12.005 ◽

2019 ◽

Vol 58 (1) ◽

pp. 100-106

Author(s):

Suzanne R. Thibodeaux ◽

Yvette C. Tanhehco ◽

Leah Irwin ◽

Lita Jamensky ◽

Kevin Schell ◽

...

Keyword(s):

Red Blood Cells ◽

Blood Cells ◽

Ex Vivo ◽

Proof Of Concept ◽

Concept Study ◽

Sickle Red Blood Cells

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Sensing of red blood cells with decreased membrane deformability by the human spleen

Blood Advances ◽

10.1182/bloodadvances.2018024562 ◽

2018 ◽

Vol 2 (20) ◽

pp. 2581-2587 ◽

Cited By ~ 11

Author(s):

Innocent Safeukui ◽

Pierre A. Buffet ◽

Guillaume Deplaine ◽

Sylvie Perrot ◽

Valentine Brousse ◽

...

Keyword(s):

Red Blood Cells ◽

Blood Cells ◽

Ex Vivo ◽

Volume Ratio ◽

Red Cells ◽

Human Spleen ◽

Rbc Membrane ◽

Membrane Rigidity ◽

Cellular Deformability ◽

Distinct Features

Abstract The current paradigm in the pathogenesis of several hemolytic red blood cell disorders is that reduced cellular deformability is a key determinant of splenic sequestration of affected red cells. Three distinct features regulate cellular deformability: membrane deformability, surface area-to-volume ratio (cell sphericity), and cytoplasmic viscosity. By perfusing normal human spleens ex vivo, we had previously showed that red cells with increased sphericity are rapidly sequestered by the spleen. Here, we assessed the retention kinetics of red cells with decreased membrane deformability but without marked shape changes. A controlled decrease in membrane deformability (increased membrane rigidity) was induced by treating normal red cells with increasing concentrations of diamide. Following perfusion, diamide-treated red blood cells (RBCs) were rapidly retained in the spleen with a mean clearance half-time of 5.9 minutes (range, 4.0-13.0). Splenic clearance correlated positively with increased membrane rigidity (r = 0.93; P < .0001). To determine to what extent this increased retention was related to mechanical blockade in the spleen, diamide-treated red cells were filtered through microsphere layers that mimic the mechanical sensing of red cells by the spleen. Diamide-treated red cells were retained in the microsphilters (median, 7.5%; range, 0%-38.6%), although to a lesser extent compared with the spleen (median, 44.1%; range, 7.3%-64.0%; P < .0001). Taken together, these results have implications for understanding the sensitivity of the human spleen to sequester red cells with altered cellular deformability due to various cellular alterations and for explaining clinical heterogeneity of RBC membrane disorders.

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Erythroblast Enucleation

Stem Cells International ◽

10.4061/2011/139851 ◽

2011 ◽

Vol 2011 ◽

pp. 1-9 ◽

Cited By ~ 55

Author(s):

Ganesan Keerthivasan ◽

Amittha Wickrema ◽

John D. Crispino

Keyword(s):

Red Blood Cells ◽

Blood Cells ◽

Ex Vivo ◽

Critical Rate ◽

Future Directions ◽

Mammalian Erythrocyte ◽

Rate Limiting

Even though the production of orthochromatic erythroblasts can be scaled up to fulfill clinical requirements, enucleation remains one of the critical rate-limiting steps in the production of transfusable red blood cells. Mammalian erythrocytes extrude their nucleus prior to entering circulation, likely to impart flexibility and improve the ability to traverse through capillaries that are half the size of erythrocytes. Recently, there have been many advances in our understanding of the mechanisms underlying mammalian erythrocyte enucleation. This review summarizes these advances, discusses the possible future directions in the field, and evaluates the prospects for improved ex vivo production of red blood cells.

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