Effect of Hemoglobin Concentration on Nucleation and Polymer Formation in Sickle Red Blood Cells

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 Methods Blood bags with CPD-SAGM stored at 4°C for 28 days were withdrawn aseptically on days 1, 14, and 28.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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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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SICKLE RED BLOOD CELLS BIND TO THE 140 kDa C-TERMINAL DOMAIN OF THROMBOSPONDIN. ▴ 921

Pediatric Research ◽

10.1203/00006450-199604001-00943 ◽

1996 ◽

Vol 39 ◽

pp. 156-156

Author(s):

C A Hillery ◽

M C Du ◽

J A French ◽

J P Scott

Keyword(s):

Red Blood Cells ◽

Blood Cells ◽

Terminal Domain ◽

Sickle Red Blood Cells

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The Effect of Experimental Escherichia coli Infection on Some Blood Parameters and Histological Changes in Male Rats

The Iraqi Journal of Veterinary Medicine ◽

10.30539/iraqijvm.v35i2.571 ◽

2011 ◽

Vol 35 (2) ◽

pp. 22-27

Author(s):

Hayder AL – Zamely

Keyword(s):

Escherichia Coli ◽

Red Blood Cells ◽

Blood Cells ◽

Histopathological Examination ◽

Hemoglobin Concentration ◽

Blood Parameters ◽

Infected Group ◽

Male Rats ◽

Control Group ◽

Renal Tubules

This study was carried out to investigate the effect of experimental infection by Escherichia coli on some blood parameters and histopathological changes in male rats to reach this objective twenty male rats (Rattus norvigicus) were divided into two groups, housed under same conditions of water, feed, temperature, light and humidity. The first one served as control group, while the second was experimentally infected with Ecoli by administration of 2ml / rat of (1×109) colony forming unit/ml of E-coli. Five days later blood were obtained from animals by cardiac puncture to measure the total and differential white blood cells count hemoglobin concentration packed cells volume red blood cells count, and thrombocytes count. One animal from each group was killed and histopathological examination was done for intestine kidney liver and spleen to detect the effect of infection on these organs. The results revealed a significant increase in total leukocytes count (P<005) in infected group while the differential count showed a significant increase in neutrophils and significant decrease in lymphocytes (P< 0.05) in same group. There were a significant decrease in hemoglobin concentration packed cell volume and non significant decrease in red blood cells count. While thrombocytes count showed a significant decrease in infected group compared with control group (P<0.05). The histopathological examination of infected male rats intestine was demonstrated mild diffuse inflammation which include increased numbers of neutrophile in tissue intraepithelial lymphocytes and goblet cells In kidney renal tubules showed extensive epithelial swelling with decreased lumen space and generalized necrotic changes with interstitial hemorrhage in renal cortex. In liver hepatocytes were swollen with decreased sinusoidal spaces and widely distributed necrotic foci were seen. There is extensive splenic necrosis with infiltration of leukocytes from white pulp to red pulp of spleen.

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Transport of 14 C-deferiprone in normal, thalassaemic and sickle red blood cells

British Journal of Haematology ◽

10.1046/j.1365-2141.1999.01447.x ◽

1999 ◽

Vol 105 (4) ◽

pp. 1081-1083 ◽

Cited By ~ 12

Author(s):

Oded Shalev ◽

Dona Hileti ◽

Philip Nortey ◽

Robert P. Hebbel ◽

Victor A. Hoffbrand

Keyword(s):

Red Blood Cells ◽

Blood Cells ◽

Sickle Red Blood Cells

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Abnormal flow adhesion of sickle red blood cells to human placental trophoblast extracellular matrix

Clinical Hemorheology and Microcirculation ◽

10.3233/ch-2011-1525 ◽

2012 ◽

Vol 51 (3) ◽

pp. 229-234 ◽

Cited By ~ 2

Author(s):

Yann Lamarre ◽

Stéphane Petres ◽

Marie-Dominique Hardy-Dessources ◽

Stéphane Sinnapah ◽

Marc Romana ◽

...

Keyword(s):

Extracellular Matrix ◽

Red Blood Cells ◽

Blood Cells ◽

Sickle Red Blood Cells

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Confined filaments in soft vesicles – the case of sickle red blood cells

Soft Matter ◽

10.1039/c9sm01872g ◽

2020 ◽

Vol 16 (2) ◽

pp. 421-427

Author(s):

Arabinda Behera ◽

Gaurav Kumar ◽

Anirban Sain

Keyword(s):

Red Blood Cells ◽

Blood Cells ◽

Sickle Red Blood Cells

Abnormal shapes of red blood cells (RBC) have been associated with various diseases.

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Dynamic spectroscopic phase microscopy for quantifying hemoglobin concentration and dynamic membrane fluctuation in red blood cells

Optics Express ◽

10.1364/oe.20.009673 ◽

2012 ◽

Vol 20 (9) ◽

pp. 9673 ◽

Cited By ~ 64

Author(s):

Yunhun Jang ◽

Jaeduck Jang ◽

YongKeun Park

Keyword(s):

Red Blood Cells ◽

Blood Cells ◽

Hemoglobin Concentration ◽

Dynamic Membrane ◽

Phase Microscopy

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Effects of Pan-Selectin Antagonist GMI-1070 on the Treatment of Vaso-Occlusion in Sickle Cell Mice

Blood ◽

10.1182/blood.v112.11.535.535 ◽

2008 ◽

Vol 112 (11) ◽

pp. 535-535 ◽

Cited By ~ 2

Author(s):

Jungshan Chang ◽

John T Patton ◽

Paul S. Frenette ◽

John L. Magnani

Keyword(s):

Blood Flow ◽

Red Blood Cells ◽

Sickle Cell ◽

Small Molecule ◽

Vascular Endothelium ◽

Intravital Microscopy ◽

Blood Cells ◽

Tnf Α ◽

Sickle Red Blood Cells ◽

Adherent Leukocytes

Abstract Acute vaso-occlusion (VOC) in patients with sickle cell disease (SCD) induces intense pain arising from organ damage and is the major cause of morbidity and mortality. Hypoxia and abnormal sickle red blood cells (RBC) induce inflammatory mediators and activation of the vascular endothelium leading to the recruitment of adherent leukocytes and sickle RBC followed by aggregates that eventually occlude blood flow. Previous studies have implicated the critical roles of cell adhesion molecules E- and P-selectins by using intravital microscopy in SCD mice (Berkeley strain) with altered genetic backgrounds (SCD transplanted in recipients lacking E-and P-selectins), or antibodies against endothelial selectins, or small molecules directed against the selectins. Here, we designed a treatment protocol for this SCD mouse model, in which a small molecule pan-selectin antagonist (GMI-1070) is administered to sickle cell mice late in the process of established vaso-occlusion in order to test the effects of GMI-1070 in a more clinically relevant model. GMI-1070 is a small molecule pan-selectin antagonist designed on the bioactive conformation of the carbohydrate ligand and inhibits leukocyte adhesion to activated endothelium in vitro with particularly strong activity against E-selectin (IC50 = 3.4 μM). Berkeley SCD mice were generated by bone marrow transplantation into lethally irradiated C57BL/6 male mice and the fully engrafted (100% donor RBC chimerism) mice were used for intravital microscopy experiments. VOC events were induced by injection with TNF-α at time 0 and the formation of occlusions were allowed to proceed as long as possible just prior to the death of the control mice. GMI-1070 (20 mg/kg) or vehicle (PBS pH 7.4) were administered at t = 110 min. Post-capillary and collecting venules in the cremaster muscle were analyzed for effects on an established VOC event. Under these conditions, GMI-1070 significantly increased the microcirculatory blood flow to levels observed in non-sickle cell mice (vehicle: 237 ± 15 nL/sec; GMI-1070: 533 ± 58 nL/sec; p<0.0001). The recruitment of adherent leukocytes to the vascular endothelium was also significantly reduced (vehicle: 2235 ± 156; GMI-1070: 1270 ± 203 cells/mm2; p=0.0013), and there were significant and dramatic reductions in the capture of sickle red blood cells to adherent leukocytes (vehicle: 0.68 ± 0.27; GMI-1070: 0.03 ± 0.01 interactions/WBC, min, 100ml; p=0.0003). Mice began to succumb to VOC within 2.5 hours after injection of TNF-α and surgical trauma which continued until all of the control SCD mice died. Administration of GMI-1070 prevented the death of half of the treated mice within the timeframe of the experiment and extended the median survival of mice from 5 hours (control, vehicle-treated) to greater than 9 hours for the GMI-1070- treated SCD mice (p = 0.0067). These studies show that GMI-1070 can significantly and dramatically improve the condition and survival of the animals with a severe VOC even when dosed well after the initiating challenge. Thus these data strongly support the use of GMI-1070 for the treatment of patients in acute vaso-occlusive crisis. GMI-1070 is currently in a Phase I clinical trial.

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