scholarly journals Priming With Red Blood Cells Allows Red Blood Cell Exchange for Sickle Cell Disease in Low-Weight Children

2021 ◽  
Vol 8 ◽  
Author(s):  
Olivier Hequet ◽  
Camille Boisson ◽  
Philippe Joly ◽  
Daniela Revesz ◽  
Kamila Kebaili ◽  
...  
Keyword(s):  
Young Children ◽  
Blood Cell ◽  
Red Blood Cells ◽  
Sickle Cell ◽  
Red Blood Cell ◽  
Blood Cells ◽  
Clinical Safety ◽  
Low Weight ◽  
Expected Values ◽  
The Impact

Red blood cell exchanges are frequently used to treat and prevent cerebrovascular complications in patients with sickle cell anemia (SCA). However, the low weight of young children represents serious concerns for this procedure. The Spectra Optia device can perform automatic priming using red blood cells (RBCs) (RCE/RBC-primed) which could allow RBC exchanges (RCE) to be performed in young children without hypovolemic complications, but this method requires evaluation. We prospectively analyzed the clinical safety of the RCE/RBC-primed procedure in 12 SCA low-weight children under either a chronic RCE program or emergency treatment over 65 sessions. We monitored grade 2 adverse events (AEs) such as a decrease in blood pressure, increase in heart rate, fainting sensation, or transfusion reactions and identified the critical times during the sessions in which AEs could occur. Post-apheresis hematocrit (Hct) and a fraction of cell remaining (FCR) values were compared to the expected values. We also compared the impact of automatic RCE (n = 7) vs. RCE/RBC-primed (n = 8) on blood viscosity and RBC rheology. A low incidence of complications was observed in the 65 RCE sessions with only seven episodes of transient grade 2 AEs. Post-apheresis Hct and FCR reached expected values with the RCE/RBC-primed method. Both the automatic and priming procedures improved RBC deformability and decreased the sickling tendency during deoxygenation. Blood rheological features improved in both RCE/RBC-primed and automatic RCE without priming conditions. The RCE/RBC-primed procedure provides blood rheological benefits, and is safe and efficient to treat, notably in young children with SCA in prophylactic programs or curatively when a SCA complication occurs.

Microfluidic electrical impedance assessment of red blood cell mediated microvascular occlusion

Lab on a Chip ◽  
2021 ◽  
Author(s):  
Yuncheng Man ◽  
Debnath Maji ◽  
Ran An ◽  
Sanjay Ahuja ◽  
Jane A Little ◽  
...  
Keyword(s):  
Sickle Cell Disease ◽  
Blood Cell ◽  
Red Blood Cells ◽  
Sickle Cell ◽  
Red Blood Cell ◽  
Blood Cells ◽  
Electrical Impedance ◽  
Cell Disease ◽  
Blood Disorders

Alterations in the deformability of red blood cells (RBCs), occurring in hemolytic blood disorders such as sickle cell disease (SCD), contributes to vaso-occlusion and disease pathophysiology. However, there are few...

scholarly journals Rapid increase in red blood cell density driven by K:Cl cotransport in a subset of sickle cell anemia reticulocytes and discocytes

Blood ◽  
1991 ◽  
Vol 78 (1) ◽  
pp. 217-225 ◽  
Author(s):  
ME Fabry ◽  
JR Romero ◽  
ID Buchanan ◽  
SM Suzuka ◽  
G Stamatoyannopoulos ◽  
...  
Keyword(s):  
Blood Cell ◽  
Red Blood Cells ◽  
Cell Density ◽  
Sickle Cell ◽  
Sickle Cell Anemia ◽  
Red Blood Cell ◽  
Blood Cells ◽  
Gradient Centrifugation ◽  
Rapid Change ◽  
Volume Regulatory Decrease

We have previously demonstrated that young normal (AA) and sickle cell anemia (SS) red blood cells are capable of a volume regulatory decrease response (VRD) driven by a K:Cl cotransporter that is activated by low pH or hypotonic conditions. We now report on the characteristics of young SS cells (SS2, discocytes) capable of rapid increase in density in response to swelling. We have isolated cells with high VRD response (H-VRD) and low VRD response (L-VRD) cells by incubation and density- gradient centrifugation under hypotonic conditions. Comparison of these cells in patients homozygous for hemoglobin (Hb)S indicated that H-VRD cells have 91% more reticulocytes (P less than 9 x 10(-9) than L-VRD cells, 25% less HbF (P less than 5.5 x 10(-5), 106% more NEM (N- methylmaleimide)-stimulated K:Cl cotransport activity (P less than 2 x 10(-4), and 86% more volume-stimulated K:Cl cotransport activity (P less than 1.8 x 10(-3). H-VRD and L-VRD cells have similar G-6-PD and Na+/H+ antiport activity. In agreement with the reduced percent HbF in H-VRD cells, F cells (red blood cells that contain fetal Hb) are depleted from the H-VRD population; however, F reticulocytes are enriched in the H-VRD population to the same extent as non-F reticulocytes, which suggests that both F and non-F reticulocytes have a similar initial distribution of volume-sensitive K:Cl cotransport activity but that it may be more rapidly inactivated in F than in S reticulocytes. We find that H-VRD cells consist of 20% reticulocytes (or 79% of all reticulocytes in SS2) and 80% more mature cells. This study demonstrates the role of K:Cl cotransport in determining red blood cell density, the heterogeneity of K:Cl cotransport activity in reticulocytes, and the capacity for rapid change in the density of reticulocytes with high K:Cl cotransport activity. We speculate that the H-VRD population may be more susceptible to generation of dense and irreversibly sickled cells.

scholarly journals Analysis of the Protein C System Under Flow and the Impact of Red Blood Cells

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 1480-1480
Author(s):  
Maria Cristina Bravo ◽  
Thomas Orfeo ◽  
Elizabeth Lavoie ◽  
Yves Dubief ◽  
Kenneth G. Mann
Keyword(s):  
Blood Cell ◽  
Red Blood Cells ◽  
Red Blood Cell ◽  
Blood Cells ◽  
Protein C ◽  
Depletion Zone ◽  
Shear Rates ◽  
Circulating Cells ◽  
The Impact ◽  
Low Shear

Abstract Introduction The rapid coagulation response to vascular injury is mediated by the formation of the extrinsictenase, intrinsictenase, and prothrombinase complexes. The prothrombotic response to injury is down-regulated by the presence of circulating active protease inhibitors as well as the protein C pathway. Protein C is activated by the thrombin-thrombomodulin complex; activated protein C (APC) then regulates thrombin generation by proteolytically inactivating factors Va and VIIIa, cofactors of the procoagulant prothrombinase and intrinsic tenasecomplexes, respectively. Previous reports have analyzed the biochemistry of the protein C system in closed systems. Our goal is to characterize the behavior of the protein C system under flow as well as the impact of circulating cells on the activation of protein C. Methods Experiments were conducted in phospholipid (3:1 ratio of synthetic phosphatidylcholine and phosphatidylserine) coated capillaries containing rabbit thrombomodulin (TM) that were preloaded with α-thrombin (αIIa) or recombinant meizothrombin (rMZ). Protein C (PC) activation was evaluated under flow at pH 7.4 and 37°C in either a buffered solution containing 2 mM CaCl2 and PC at its mean physiological concentration (65 nM) or in a mock blood mixture containing 60% of buffer containing 65 nM PC and 40% freshly prepared washed red blood cells; shear rates ranged from 100-1000 s-1. Capillary effluents were collected and then assayed for APC levels using a modified aPTT assay. To establish whether PC activation is under dilutional or diffusional control, the steady state concentrations of APC achieved at different shears were normalized to the residence time of one capillary volume specific for each shear rate. The efficiency of PC activation was also analyzed by normalizing the amount of APC generated to the amount of PC present in the mixture (1.3 pmol PC in buffer only vs. 0.78 pmol of PC in mock blood trials). Results At low shear rates (100 s-1 and 250 s-1) in the buffer only system the rMZ•TM complex generates 42-55% higher levels of APC than the αIIa•TM complex. Protein C activation by the αIIa-TM complex appears to be dilutionally controlled at shear rates ≥ 500 s-1, while diffusionally controlled at lower shear rates (≤ 250 s-1). The inclusion of red blood cells in the reaction system under flow resulted in a broader range of dilutional control (≥ 250 s-1) compared to the buffer only system (≥ 500 s-1). Normalization of the data to account for the differential amount of protein C present in a given volume indicate a two-fold greater efficiency of PC activation in the presence of red blood cells (14.7 ± 1.2 mol APC•mol-1 PC•min-1•cm-2) compared to buffer alone (6.7 ± 0.6 mol APC•mol-1 PC•min-1•cm-2). Conclusions In the presence of catalytically inert red blood cells the activation of protein C is regulated by diffusion only at the lowest shear rates tested (100 s-1). These data suggest that the dynamics and aggregation of red blood cell effects are shear dependent as red blood cells deform and migrate toward the center of the channel at increasing shear rates. We can hypothesize that at high shear rates (≥ 500 s-1), when the levels of APC generated in the red blood cell system and buffer only system are similar, the excluded volume created by the red blood cells agglomerated at the center of the capillary leaves a cell-free region adjacent to the wall which is large enough to accommodate the space needed for surface catalysis (depletion zone). Indeed the adjustment of PC concentration for excluded volume in red blood cell solutions yields the same concentration of APC generated as in the buffer solution. However, at low shear rates (100 s-1) the red blood cells do not create a distinct channel and the depletion zone extending from the capillary wall overlaps with red blood cells and maintains the diffusional control of the protein C system. These studies provide a foundation for studying the impact of circulating cells on the biochemistry of the coagulation cascade Disclosures No relevant conflicts of interest to declare.

scholarly journals Rapid increase in red blood cell density driven by K:Cl cotransport in a subset of sickle cell anemia reticulocytes and discocytes

Blood ◽  
1991 ◽  
Vol 78 (1) ◽  
pp. 217-225 ◽  
Author(s):  
ME Fabry ◽  
JR Romero ◽  
ID Buchanan ◽  
SM Suzuka ◽  
G Stamatoyannopoulos ◽  
...  
Keyword(s):  
Blood Cell ◽  
Red Blood Cells ◽  
Cell Density ◽  
Sickle Cell ◽  
Sickle Cell Anemia ◽  
Red Blood Cell ◽  
Blood Cells ◽  
Gradient Centrifugation ◽  
Rapid Change ◽  
Volume Regulatory Decrease

Abstract We have previously demonstrated that young normal (AA) and sickle cell anemia (SS) red blood cells are capable of a volume regulatory decrease response (VRD) driven by a K:Cl cotransporter that is activated by low pH or hypotonic conditions. We now report on the characteristics of young SS cells (SS2, discocytes) capable of rapid increase in density in response to swelling. We have isolated cells with high VRD response (H-VRD) and low VRD response (L-VRD) cells by incubation and density- gradient centrifugation under hypotonic conditions. Comparison of these cells in patients homozygous for hemoglobin (Hb)S indicated that H-VRD cells have 91% more reticulocytes (P less than 9 x 10(-9) than L-VRD cells, 25% less HbF (P less than 5.5 x 10(-5), 106% more NEM (N- methylmaleimide)-stimulated K:Cl cotransport activity (P less than 2 x 10(-4), and 86% more volume-stimulated K:Cl cotransport activity (P less than 1.8 x 10(-3). H-VRD and L-VRD cells have similar G-6-PD and Na+/H+ antiport activity. In agreement with the reduced percent HbF in H-VRD cells, F cells (red blood cells that contain fetal Hb) are depleted from the H-VRD population; however, F reticulocytes are enriched in the H-VRD population to the same extent as non-F reticulocytes, which suggests that both F and non-F reticulocytes have a similar initial distribution of volume-sensitive K:Cl cotransport activity but that it may be more rapidly inactivated in F than in S reticulocytes. We find that H-VRD cells consist of 20% reticulocytes (or 79% of all reticulocytes in SS2) and 80% more mature cells. This study demonstrates the role of K:Cl cotransport in determining red blood cell density, the heterogeneity of K:Cl cotransport activity in reticulocytes, and the capacity for rapid change in the density of reticulocytes with high K:Cl cotransport activity. We speculate that the H-VRD population may be more susceptible to generation of dense and irreversibly sickled cells.

scholarly journals Red Blood Cell Alloimmunization in Sickle Cell Disease Patients in Jeddah, Saudi Arabia: A Pilot Study.

2015 ◽  
Vol 22 (3) ◽  
pp. 34-40
Author(s):  
Abdulrahman S. Alboog ◽  
Taher M. Tayeb ◽  
Mohammed O. Alsager ◽  
Salwa A. AlNajjar ◽  
Ghazi A. Damanhouri ◽  
...  
Keyword(s):  
Saudi Arabia ◽  
Sickle Cell Disease ◽  
Blood Cell ◽  
Red Blood Cells ◽  
Sickle Cell ◽  
Red Blood Cell ◽  
Blood Cells ◽  
University Hospital ◽  
Cell Disease ◽  
Significant Difference

The treatment of patients with sickle cell disease frequently requires transfusion of red blood cells. Complications due to alloimmunization of red blood cells antigen remain a major risk as a post transfusion effect. The objective of this study is to determine the frequency of red cell alloimmunization in Jeddah, Saudi Arabia. A retrospective cross-section study of sickle cell disease patients at King Abdulaziz University Hospital between 2012 and 2013 was performed. Demographic characteristics and transfusion history was recorded. Blood samples were analyzed for alloimmunization using immunohematological technique. A total of 234 sickle cell patients were analyzed, of which 30 (12.8%) showed alloantibodies. A total of 43 alloantibodies were found out of which 28 belonged to Rh group, eight belonged to Kell while three belonged to MNS group. Demographic and transfusion characteristics were analyzed between alloimmunized and nonalloimmunized sickle cell disease patients. The rate of alloimmunization in Jeddah, Saudi Arabia was 12.8%. There was significant difference observed between alloantibodies detection between transfused patients compared to non-transfused patients. The consequences of red blood cell alloimmunization are highly significant and therefore immune hematological testing is highly recommended.  

scholarly journals Metabolic impact of red blood cell exchange with rejuvenated red blood cells in sickle cell patients

Transfusion ◽  
2019 ◽  
Vol 59 (10) ◽  
pp. 3102-3112 ◽  
Author(s):  
Sarah Gehrke ◽  
Nirmish Shah ◽  
Fabia Gamboni ◽  
Reed Kamyszek ◽  
Amudan J. Srinivasan ◽  
...  
Keyword(s):  
Blood Cell ◽  
Red Blood Cells ◽  
Sickle Cell ◽  
Red Blood Cell ◽  
Blood Cells

scholarly journals Characterization and statistical modeling of glycosylation changes in sickle cell disease

2021 ◽  
Vol 5 (5) ◽  
pp. 1463-1473
Author(s):  
Heather E. Ashwood ◽  
Christopher Ashwood ◽  
Anna P. Schmidt ◽  
Rebekah L. Gundry ◽  
Karin M. Hoffmeister ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Sickle Cell Disease ◽  
Blood Cell ◽  
Red Blood Cells ◽  
Blood Group ◽  
Sickle Cell ◽  
Red Blood Cell ◽  
Blood Cells ◽  
Blood Group Antigens ◽  
Cell Disease

AbstractSickle cell disease is an inherited genetic disorder that causes anemia, pain crises, organ infarction, and infections in 13 million people worldwide. Previous studies have revealed changes in sialic acid levels associated with red blood cell sickling and showed that stressed red blood cells bare surface-exposed clustered terminal mannose structures mediating hemolysis, but detailed glycan structures and anti-glycan antibodies in sickle cell disease remain understudied. Here, we compiled results obtained through lectin arrays, glycan arrays, and mass spectrometry to interrogate red blood cell glycoproteins and glycan-binding proteins found in the plasma of healthy individuals and patients with sickle cell disease and sickle cell trait. Lectin arrays and mass spectrometry revealed an increase in α2,6 sialylation and a decrease in α2,3 sialylation and blood group antigens displayed on red blood cells. Increased binding of proteins to immunogenic asialo and sialyl core 1, Lewis A, and Lewis Y structures was observed in plasma from patients with sickle cell disease, suggesting a heightened anti-glycan immune response. Data modeling affirmed glycan expression and plasma protein binding changes in sickle cell disease but additionally revealed further changes in ABO blood group expression. Our data provide detailed insights into glycan changes associated with sickle cell disease and refer glycans as potential therapeutic targets.

Permeation of the luminal capillary glycocalyx is determined by hyaluronan

1999 ◽  
Vol 277 (2) ◽  
pp. H508-H514 ◽  
Author(s):  
Charmaine B. S. Henry ◽  
Brian R. Duling
Keyword(s):  
Blood Cell ◽  
Red Blood Cells ◽  
Red Blood Cell ◽  
Blood Cells ◽  
Enzyme Treatment ◽  
Apical Surface ◽  
Bright Field ◽  
Endothelial Surface ◽  
The Difference

The endothelial cell glycocalyx influences blood flow and presents a selective barrier to movement of macromolecules from plasma to the endothelial surface. In the hamster cremaster microcirculation, FITC-labeled Dextran 70 and larger molecules are excluded from a region extending almost 0.5 μm from the endothelial surface into the lumen. Red blood cells under normal flow conditions are excluded from a region extending even farther into the lumen. Examination of cultured endothelial cells has shown that the glycocalyx contains hyaluronan, a glycosaminoglycan which is known to create matrices with molecular sieving properties. To test the hypothesis that hyaluronan might be involved in establishing the permeation properties of the apical surface glycocalyx in vivo, hamster microvessels in the cremaster muscle were visualized using video microscopy. After infusion of one of several FITC-dextrans (70, 145, 580, and 2,000 kDa) via a femoral cannula, microvessels were observed with bright-field and fluorescence microscopy to obtain estimates of the anatomic diameters and the widths of fluorescent dextran columns and of red blood cell columns (means ± SE). The widths of the red blood cell and dextran exclusion zones were calculated as one-half the difference between the bright-field anatomic diameter and the width of the red blood cell column or dextran column. After 1 h of treatment with active Streptomyces hyaluronidase, there was a significant increase in access of 70- and 145-kDa FITC-dextrans to the space bounded by the apical glycocalyx, but no increase in access of the red blood cells or in the anatomic diameter in capillaries, arterioles, and venules. Hyaluronidase had no effect on access of FITC-Dextrans 580 and 2,000. Infusion of a mixture of hyaluronan and chondroitin sulfate after enzyme treatment reconstituted the glycocalyx, although treatment with either molecule separately had no effect. These results suggest that cell surface hyaluronan plays a role in regulating or establishing permeation of the apical glycocalyx to macromolecules. This finding and our prior observations suggest that hyaluronan and other glycoconjugates are required for assembly of the matrix on the endothelial surface. We hypothesize that hyaluronidase creates a more open matrix, enabling smaller dextran molecules to penetrate deeper into the glycocalyx.

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