scholarly journals Does Higher Red Blood Cell (RBC) Lactate Transporter Activity Explain Impaired RBC Deformability in Sickle Cell Trait?

2005 ◽  
Vol 55 (6) ◽  
pp. 385-387 ◽  
Author(s):  
Philippe Connes ◽  
Fagnété Sara ◽  
Marie-Dominique Hardy-Dessources ◽  
Maryse Etienne-Julan ◽  
Olivier Hue
Keyword(s):  
Blood Cell ◽  
Sickle Cell ◽  
Red Blood Cell ◽  
Sickle Cell Trait ◽  
Lactate Transporter ◽  
Rbc Deformability

scholarly journals Hypoxia Impact on Red Blood Cell-Mediated Microvascular Occlusion and Adhesion in Sickle Cell Disease and Sickle Cell Trait

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 966-966
Author(s):  
Yuncheng Man ◽  
Zoe Sekyonda ◽  
Karamoja Monchamp ◽  
Ran An ◽  
Erdem Kucukal ◽  
...  
Keyword(s):  
Sickle Cell Disease ◽  
Blood Cell ◽  
Sickle Cell ◽  
Red Blood Cell ◽  
Whole Blood ◽  
Sickle Cell Trait ◽  
Single Gene ◽  
Cell Disease ◽  
The Impact ◽  
Rbc Deformability

Abstract Introduction: Sickle cell disease (SCD) is a recessively inherited anemia caused by a single gene mutation leading to sickle hemoglobin production. Sickle cell trait (SCT) is the carrier state. Abnormal hemoglobin polymerization and resultant red blood cell (RBC) sickling, decreased deformability and increased adhesion, are well-known features of homozygous SCD. However, the overall pathophysiological impact of SCT on the RBC remains incompletely characterized. Here we use microfluidic techniques designed by us, the OcclusionChip and SCD Biochip (previously published), and commercially available ektacytometry to investigate hypoxia impact on RBC biophysical properties in SCT. Methods: Venous blood samples were collected in EDTA from subjects with homozygous HbSS, SCT (HbAS), and non-anemic controls (HbAA) under an IRB-approved protocol. OcclusionChip devices were fabricated using standard soft lithography protocols [1]. RBCs were isolated from whole blood, re-suspended in PBS at 20% hematocrit, and passed through the OcclusionChip device with a constant inlet pressure. Following a wash step, the OcclusionChip microchannel was imaged, and Occlusion Index (OI), a standardized generalizable parameter we developed, representing the overall microcapillary network occlusion, was quantified. SCD Biochip microchannels were fabricated by lamination and were functionalized with human laminin (LN-511) [2]. Undiluted whole blood was injected into the microchannel at 1 dyne/cm 2, a shear stress value typically observed in the post-capillary venules. Following a wash step, the SCD Biochip microchannel was imaged, and the number of adherent RBCs in a 32-mm 2 window was quantified. For hypoxia experiments, a hypoxic setup was fabricated for blood deoxygenation (pO 2 ~45 mmHg) [3, 4]. Ektacytometry measurements were performed according to the manufacturers' specifications (Lorrca Maxsis). Data are reported as mean ± standard deviation (SD). Results: We initially analyzed RBC-mediated microvascular occlusion under normoxia or hypoxia using the OcclusionChip (Figure 1A). Under normoxia, HbSS-containing RBCs had relatively greater OI values compared to HbAA- and HbAS-containing RBCs (Figure 1B, P = 0.057 for HbSS vs HbAA and P = 0.060 for HbSS vs HbAS). However, exposure to hypoxia led to significantly elevated OI values in the HbAS- and HbSS-containing RBCs (Figure 1B, 0.05 ± 0.02% vs 33.62 ± 18.31%, P = 0.015 for HbAS, and 0.27 ± 0.24% vs 49.37 ± 24.47%, P = 0.001 for HbSS, normoxia vs hypoxia). Negligible occlusion was observed in HbAA-containing RBCs (Figure 1B). We then analyzed RBC adhesion to LN under normoxia or hypoxia using the SCD Biochip (Figure 1C). Hypoxia led to greater number of adherent RBCs on LN in the HbSS-containing RBCs (Figure 1D, 141 ± 91 vs 497 ± 392, P = 0.089, normoxia vs hypoxia), but this effect was not present in HbAA- or HbAS-containing RBCs (Figure 1B, 2 ± 1 vs 3 ± 1, P > 0.05 for HbAA, and 10 ± 7 vs 12 ± 3, P > 0.05 for HbAS, normoxia vs hypoxia). Further, under normoxia, we found that the HbAS-containing RBCs had slightly greater number of adherent RBCs on LN compared to the HbAA-containing RBCs (Figure 1D, P = 0.057 for HbAA vs HbAS). As previously reported, HbSS-containing RBCs showed greatest adhesion to LN under normoxia compared to the HbAA- and HbAS-containing RBCs (Figure 1D, P = 0.027 for HbSS vs HbAA and P = 0.033 for HbSS vs HbAS)., Finally, we preformed Lorrca oxyscan and found that ektacytometry is less sensitive to RBC deformability change under hypoxia in SCT (Figure 1E). Conclusions: Findings in this study suggest that although RBCs from subjects with SCT are deformable under normoxia and are able to clear narrow capillaries similar to normal RBCs, hypoxia changes deformability, presumably due to hypoxic polymer formation, and could contribute to microvascular occlusion in SCT. The OcclusionChip is a single cell-based technology, and may be more sensitive to single RBC deformability. Future studies will prospectively focus on analyzing RBC adhesion on activated microvascular endothelial cells in physiologic flow to further interrogate the impact of hypoxia on pathophysiology in SCT. References: [1] Man et al., LabChip, 2020, 20, 2086-2099. [2] Kim et al., Microcirculation, 2017, 24, e12374. Figure 1 Figure 1. Disclosures An: Hemex Health, Inc.: Patents & Royalties. Kucukal: BioChip Labs: Current Employment, Patents & Royalties. Nayak: BioChip Labs: Patents & Royalties. Little: Biochip Labs: Patents & Royalties; Hemex Health, Inc.: Patents & Royalties. Gurkan: Dx Now Inc.: Patents & Royalties; Hemex Health, Inc.: Current Employment, Patents & Royalties; Biochip Labs: Patents & Royalties; Xatek Inc.: Patents & Royalties.

Red Blood Cell Deformability Demonstrated with the Oxygenscan: Exploring the Association with Hydroxyurea Treatment, Co-Inherited α-Thalassemia, and Frequency of Pain in Children with Sickle Cell Anemia

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 4834-4834
Author(s):  
Amina Nardo-Marino ◽  
Jesper Petersen ◽  
Andreas Glenthoej ◽  
John N. Brewin ◽  
Joergen Kurtzhals ◽  
...  
Keyword(s):  
Blood Cell ◽  
Sickle Cell ◽  
Sickle Cell Anemia ◽  
Red Blood Cell ◽  
Hemoglobin F ◽  
Positive Correlation ◽  
King's College ◽  
Hydroxyurea Treatment ◽  
Pain Frequency ◽  
Rbc Deformability

Background Sickle hemoglobin (hemoglobin S, HbS) is a structural variant of adult hemoglobin. HbS polymerizes when oxygen tensions are low, leading to red blood cell (RBC) deformation, so-called "sickling". In sickle cell anemia (SCA), loss of RBC deformability is considered to be a primary factor responsible for vaso-occlusion and hemolysis. Until recently no laboratory tests to measure RBC deformability in SCA have been readily available. Study Aims In this study we examine RBC deformability, measured with the oxygenscan module of the Laser Optical Rotational Red Cell Analyzer (Lorrca) ektacytometer, in children with SCA treated with or without hydroxyurea (HU). Furthermore, we investigate the relationship between RBC deformability and pain frequency, as well as genetic and laboratory measures known to be associated with disease severity in SCA. Methods We included children aged 0-16 years with a confirmed diagnosis of SCA (HbSS) from the pediatric sickle cell clinic at King's College Hospital in London. Children were excluded if they had received any blood transfusions within 3 months of study inclusion. Children on HU were only included if treatment had been initiated >3 months prior to recruitment and the dose was stable. Children and their parents or guardians reported frequency of pain as: daily, weekly, monthly, yearly, or never. Laboratory measurements, including total hemoglobin (hb), hemoglobin F (HbF), and reticulocyte percentage, were performed on the same day as a sample was taken for oxygenscan analysis. Data on co-inheritance of α-thalassemia was recorded if available. EDTA blood samples were kept at approximately 4°C and transported from King's College London to Copenhagen University Hospital (Herlev and Gentofte Hospital), where they were analyzed within 48 hours of sampling using the Lorrca oxygenscan (RR Mechatronics, the Netherlands). The oxygenscan measures RBC deformability expressed as an elongation index (EI) during deoxygenation and reoxygenation, with EImax expressing RBC deformability at normal oxygen concentrations, EImin expressing RBC deformability after deoxygenation, and the point of sickling (POS) expressing the point at which >5% decrease in EI is observed, representing the pO2 at which sickling begins. All statistical analyses were performed in Stata V16.0 (StataCorp. 2019, USA), using the two-sided t-test, one-way ANOVA, and Pearson's correlation when appropriate. Results We included 47 children aged 0-16 years (mean age 7.9 years) in the study, 24 (51%) receiving HU. Children in the HU group presented with significantly higher HbF percentage compared to the non-HU group (15.6% and 10.9%, p=0.03). Children receiving HU had higher EImax and EImin, and lower POS values, compared to children in the non-HU group, although results were not significant (Table 1). There was a positive correlation between HbF and EImax (r= 0.57, p=0.0001) and HbF and EImin (r= 0.56, p=0.0001), and a negative correlation between HbF and POS (r=-0.37, p=0.01), as well as a positive correlation between total hb and EImax (r=0.35, p=0.02). There was no significant correlation between any oxygenscan parameters and reticulocyte percentage. Data on α-thalassemia was available for 23 children. EImax and EImin values were higher in heterozygous children compared to children without co-inherited α-thalassemia, and POS values were lower, but results were not significant (Table 2). We found no significant association between any oxygenscan parameters and pain frequency (Table 3). Conclusion In this study we identified a strong correlation between all oxygenscan parameters and HbF percentage, as has been reported previously. We found higher EImax and EImin and lower POS values in children receiving HU treatment and children with co-inherited heterozygous α-thalassemia, suggesting increased RBC deformability in these children. These results were not significant, however, which may in part be due to lack of power in the study. Also, it is possible that children in the HU group would have presented with lower EImax and EImin and higher POS values prior to HU initiation, with treatment response leading to results similar to those found in the non-HU group. Finally, our results suggest that there is no association between oxygenscan parameters and self-reported frequency of pain in children with SCA. Disclosures No relevant conflicts of interest to declare.

In Vitro Impact of Treatment With Aqueous Extract of Cassia Fistula on Red Blood Cell Sickling in Individuals With Sickle Cell Trait

2015 ◽  
Vol 10 (4) ◽  
Author(s):  
Nazanin Heidari ◽  
Foad Halvaji ◽  
Parisa Rezaei Mofrad ◽  
Mohammad Ali Jalali Far ◽  
Mohammad Taha Jalali ◽  
...  
Keyword(s):  
Blood Cell ◽  
Sickle Cell ◽  
Aqueous Extract ◽  
Red Blood Cell ◽  
Sickle Cell Trait ◽  
Cassia Fistula

Brief Research Report: Mortality Associated With the Use of Upper-Body Control Holds by Police

1990 ◽  
Vol 5 (3) ◽  
pp. 215-222 ◽  
Author(s):  
James A. Mercy ◽  
Clark W. Heath ◽  
Mark L. Rosenberg
Keyword(s):  
Blood Cell ◽  
Sickle Cell ◽  
Red Blood Cell ◽  
Sickle Cell Trait ◽  
Police Department ◽  
Upper Body ◽  
Research Report ◽  
Autopsy Findings ◽  
Police Reports ◽  
Police Records

A review of police records for the nine-year period from 1974 to 1982 identified 20 men who died following restraint by an upper-body control hold while in the custody of a large, urban police department. Using evidence from autopsy findings and police reports of events immediately preceding death, we concluded that control-hold use was associated with death in 19 of the 20 cases. This investigation points to three factors potentially associated with control hold-related death that deserve further investigation: Phencyclidine (PCP) use, sickle cell trait, and stress-related arrhythmias in the heart. PCP was detected in blood or other tissues from 6 of 17 decedents tested. Intravascular red blood cell sickling was found at autopsy in 4 of 14 black decedents (29%). Four decedents had some indication of cardiovascular abnormalities.

Effects of hydration and dehydration on blood rheology in sickle cell trait carriers during exercise

2010 ◽  
Vol 299 (3) ◽  
pp. H908-H914 ◽  
Author(s):  
Julien Tripette ◽  
Gylna Loko ◽  
Abdoulaye Samb ◽  
Bertin Doubi Gogh ◽  
Estelle Sewade ◽  
...  
Keyword(s):  
Body Weight ◽  
Blood Cell ◽  
Sickle Cell ◽  
Red Blood Cell ◽  
Blood Viscosity ◽  
Sickle Cell Trait ◽  
Blood Rheology ◽  
Plasma Viscosity ◽  
Adequate Hydration ◽  
Cont Group

This study compared the hemorheological responses of a group of sickle cell trait (SCT) carriers with those of a control (Cont) group in response to 40 min of submaximal exercise (exercise intensity, 55% aerobic peak power) performed in two conditions: one with water offered ad libitum, i.e., the hydration (Hyd) condition, and one without water, i.e., the dehydration (Dehyd) condition. Blood and plasma viscosities, as well as red blood cell rigidity, were determined at rest, at the end of exercise, and at 2 h recovery with a cone plate viscometer at high shear rate and 37°C. The SCT and Cont groups lost 1 ± 0.7 and 1.6 ± 0.6 kg of body weight, respectively, in the Dehyd condition, indicating a significant effect of water deprivation compared with the Hyd condition, in which body weight remained unchanged. Plasma viscosity increased with exercise and returned to baseline during recovery independently of the group and condition. As previously demonstrated, resting blood viscosity was greater in the SCT carriers than in the Cont group. Blood viscosity increased by the end of exercise and returned to baseline at 2 h recovery in the Cont group in both conditions. The blood viscosity of SCT carriers did not change in response to exercise in the Dehyd condition and remained elevated at 2 h recovery. This extended hyperviscosity, in association with other biological changes induced by exercise, could be considered as a risk factor for exercise-related events in SCT carriers, similar to vasoocclusive crises, notably during the recovery. In contrast, the Hyd condition normalized the hyperviscosity and red blood cell rigidity of the SCT carriers, with blood viscosity values reaching the same lower values as those found in the Cont group during the recovery. Adequate hydration of SCT carriers should be strongly promoted to reduce the clinical risk associated with potential hyperviscosity complications.

scholarly journals Red blood cell changes during the evolution of the sickle cell painful crisis

Blood ◽  
1992 ◽  
Vol 79 (8) ◽  
pp. 2154-2163 ◽  
Author(s):  
SK Ballas ◽  
ED Smith
Keyword(s):  
Blood Cell ◽  
Sickle Cell ◽  
Red Blood Cell ◽  
Reticulocyte Count ◽  
Hemoglobin Level ◽  
Second Phase ◽  
Osmotic Gradient ◽  
Cell Changes ◽  
Painful Crisis ◽  
Rbc Deformability

Abstract A longitudinal study of the red blood cell (RBC) deformability, percent of dense erythrocytes, and hematologic parameters has been conducted during 117 painful crises affecting 36 patients with sickle cell anemia between January, 1985 and December, 1990. RBC deformability was determined by osmotic gradient ektacytometry and the percentage of dense cells was quantitated by centrifugation on a discontinuous Stractan density gradient. The data indicate that the painful crisis is a process that follows a bimodal form of evolution. The first phase of the painful crisis is characterized by increase in the severity of pain, increase in the number of dense cells, and a decrease in RBC deformability. In some patients the changes in dense cells and RBC deformability are evident 1 to 3 days before the onset of pain. In addition, the hemoglobin level decreases and the reticulocyte count increases during this initial phase. The second phase of the crisis is characterized by reduction in pain intensity, decrease in the number of dense cells, and increase in RBC deformability to values higher than those seen in the steady state. Moreover, the improvement in RBC deformability and the decrease in the number of dense cells at the end of a crisis seem to constitute new risk factors that may incite a recurrence of the crisis within 1 month in about 50% of painful episodes. The pathophysiologic events responsible for this bimodal behavior of RBCs during painful episodes may represent the appearance of factors that induce (1) preferential trapping of deformable cells in the microcirculation during the first phase of the crisis, followed by a decrease of dense cells and the appearance of new deformable RBCs released from the bone marrow during the second phase of the crisis; or (2) variable sickling of all circulating RBCs during the first phase followed by disappearance of dense RBCs and their replenishment by deformable cells during the second phase.

scholarly journals Cryopreserving and deglycerolizing sickle cell trait red blood cell components using an automated cell-processing system

2020 ◽  
Vol 24 (3) ◽  
pp. 107-111
Author(s):  
Ricci Jo Ackley ◽  
A. Hallie Lee-Stroka ◽  
Barbara J. Bryant ◽  
David F. Stroncek ◽  
Karen M. Byrne
Keyword(s):  
Blood Cell ◽  
Sickle Cell ◽  
Red Blood Cell ◽  
Sickle Cell Trait ◽  
Processing System ◽  
Cell Processing ◽  
Cell Components

scholarly journals Epinephrine Modulates BCAM/Lu and ICAM-4 Expression on the Sickle Cell Trait Red Blood Cell Membrane

2012 ◽  
Vol 102 (5) ◽  
pp. 1137-1143 ◽  
Author(s):  
Jamie L. Maciaszek ◽  
Biree Andemariam ◽  
Greg Huber ◽  
George Lykotrafitis
Keyword(s):  
Cell Membrane ◽  
Blood Cell ◽  
Sickle Cell ◽  
Red Blood Cell ◽  
Sickle Cell Trait ◽  
Red Blood Cell Membrane

scholarly journals Red blood cell changes during the evolution of the sickle cell painful crisis

Blood ◽  
1992 ◽  
Vol 79 (8) ◽  
pp. 2154-2163 ◽  
Author(s):  
SK Ballas ◽  
ED Smith
Keyword(s):  
Blood Cell ◽  
Sickle Cell ◽  
Red Blood Cell ◽  
Reticulocyte Count ◽  
Hemoglobin Level ◽  
Second Phase ◽  
Osmotic Gradient ◽  
Cell Changes ◽  
Painful Crisis ◽  
Rbc Deformability

A longitudinal study of the red blood cell (RBC) deformability, percent of dense erythrocytes, and hematologic parameters has been conducted during 117 painful crises affecting 36 patients with sickle cell anemia between January, 1985 and December, 1990. RBC deformability was determined by osmotic gradient ektacytometry and the percentage of dense cells was quantitated by centrifugation on a discontinuous Stractan density gradient. The data indicate that the painful crisis is a process that follows a bimodal form of evolution. The first phase of the painful crisis is characterized by increase in the severity of pain, increase in the number of dense cells, and a decrease in RBC deformability. In some patients the changes in dense cells and RBC deformability are evident 1 to 3 days before the onset of pain. In addition, the hemoglobin level decreases and the reticulocyte count increases during this initial phase. The second phase of the crisis is characterized by reduction in pain intensity, decrease in the number of dense cells, and increase in RBC deformability to values higher than those seen in the steady state. Moreover, the improvement in RBC deformability and the decrease in the number of dense cells at the end of a crisis seem to constitute new risk factors that may incite a recurrence of the crisis within 1 month in about 50% of painful episodes. The pathophysiologic events responsible for this bimodal behavior of RBCs during painful episodes may represent the appearance of factors that induce (1) preferential trapping of deformable cells in the microcirculation during the first phase of the crisis, followed by a decrease of dense cells and the appearance of new deformable RBCs released from the bone marrow during the second phase of the crisis; or (2) variable sickling of all circulating RBCs during the first phase followed by disappearance of dense RBCs and their replenishment by deformable cells during the second phase.

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