Erythrocyte Aggregation as a Determinant of Blood Flow: Effect of pH, Temperature and Osmotic Pressure

Maeda, Nobuji; Seike, Masahiko; Kon, Kazunori; Shiga, Tohru

doi:10.1007/978-1-4615-9510-6_68

Cited by 16 publications

(8 citation statements)

References 7 publications

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“…These clumps could contribute as well to microvascular occlusion in larger capillaries, of cross-sectional diameter up to 20 µm [ 115 , 119 ], elsewhere in the body. Vascular occlusion would be promoted even though such stacked RBC clumps (rouleaux) typically dynamically aggregate and disaggregate [ 120 , 121 , 122 ], as do RBC aggregates that can form in the absence of pathogens, promoted by macromolecules in plasma under conditions of low blood shear rates [ 123 , 124 ]. Formation of RBC rouleaux would increase blood viscosity [ 121 , 122 ], impeding blood flow, especially in the small-diameter pulmonary capillaries, which would cascade as reduction in both flow velocity and associated shear forces would in turn tend to favor aggregation vs. disaggregation and further occlude flow [ 121 ].…”

Section: Properties Of Sars-cov-2 Related To Its Array Of Spike Glyco...mentioning

confidence: 99%

A Deadly Embrace: Hemagglutination Mediated by SARS-CoV-2 Spike Protein at Its 22 N-Glycosylation Sites, Red Blood Cell Surface Sialoglycoproteins, and Antibody

Scheim¹

2022

IJMS

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Rouleaux (stacked clumps) of red blood cells (RBCs) observed in the blood of COVID-19 patients in three studies call attention to the properties of several enveloped virus strains dating back to seminal findings of the 1940s. For COVID-19, key such properties are: (1) SARS-CoV-2 binds to RBCs in vitro and also in the blood of COVID-19 patients; (2) although ACE2 is its target for viral fusion and replication, SARS-CoV-2 initially attaches to sialic acid (SA) terminal moieties on host cell membranes via glycans on its spike protein; (3) certain enveloped viruses express hemagglutinin esterase (HE), an enzyme that releases these glycan-mediated bindings to host cells, which is expressed among betacoronaviruses in the common cold strains but not the virulent strains, SARS-CoV, SARS-CoV-2 and MERS. The arrangement and chemical composition of the glycans at the 22 N-glycosylation sites of SARS-CoV-2 spike protein and those at the sialoglycoprotein coating of RBCs allow exploration of specifics as to how virally induced RBC clumping may form. The in vitro and clinical testing of these possibilities can be sharpened by the incorporation of an existing anti-COVID-19 therapeutic that has been found in silico to competitively bind to multiple glycans on SARS-CoV-2 spike protein.

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Section: Properties Of Sars-cov-2 Related To Its Array Of Spike Glyco...mentioning

confidence: 99%

A Deadly Embrace: Hemagglutination Mediated by SARS-CoV-2 Spike Protein at Its 22 N-Glycosylation Sites, Red Blood Cell Surface Sialoglycoproteins, and Antibody

Scheim¹

2022

IJMS

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“…30,31 Nonetheless, there is evidence which demonstrates an increase in RBC aggregation velocities in response to a rise in temperature. 32,33 In any case, the in vitro determination of the AI described herein would negate any meaningful temperaturerelated effects since the aggregometer temperature was standardized throughout the course of the study.…”

Section: Discussionmentioning

confidence: 99%

Erythrocyte Aggregation and Blood Viscosity is Similar in Homozygous Sickle Cell Disease Patients with and without Leg Ulcers

2018

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There is no consensus regarding the role of red blood cell (RBC) aggregation in the pathogenesis of leg ulcers (LUs) in sickle cell disease (SCD). We sought to evaluate whether the cross-sectional determination of RBC aggregation and hematological indices were associated with the presence of LU in homozygous SCD. Twenty-seven patients with LU and 23 with no history of ulceration were recruited into the study. A laser-assisted rotational red cell analyzer (LoRRca) was used in the determination of the aggregation index (AI), aggregation half-time ( ), and the RBC aggregate strength (AMP). Hematological indices were determined using a CELL-DYN Ruby analyzer. Whole blood viscosity (WBV) and plasma viscosity (PV) were measured using a Vilastic bioprofiler. The data were presented as means ± standard deviation or median, interquartile range. Two-sample -test was used to test for associations between the AIs, WBV, and PV in patients with and without LU. Statistical significance was taken as < 0.05. All analyses were conducted using Stata/SE . 12.1 (StataCorp, College Station, TX). The AI was comparable in the group with and without ulcers (68.6, 16.7 versus 67.7, 16.9; = 0.74); (1.7, 1.3 versus 1.8, 1.3; = 0.71); AMP (18.8, 14.5 versus 19.1, 13.3; = 0.84), WBV (3.8, 1.2 versus 3.8, 0.7; = 0.77); and the PV (1.3, 0.08 versus 1.4, 0.1; = 0.31) and were also not statistically different between the groups of participants. RBC aggregation and aggregate strength are not associated with leg ulceration in SCD.

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“…Initially transient obstructions would reduce the speed of blood flow, in turn enabling formation of more catches and clumps in a cascade of microvascular occlusion. Highlighting the potential for such virally mediated hemagglutination is the aggregation of RBCs that can occur even without the presence of virus, joined by macromolecules in plasma, under conditions of low blood flow shear rates [172] such as in veins [173]. Such hemagglutination is reversible, the RBCs separating at higher shear rates [172].…”

Section: "Catch and Clump" Occlusion Of The Microvasculaturementioning

confidence: 99%

“…Highlighting the potential for such virally mediated hemagglutination is the aggregation of RBCs that can occur even without the presence of virus, joined by macromolecules in plasma, under conditions of low blood flow shear rates [172] such as in veins [173]. Such hemagglutination is reversible, the RBCs separating at higher shear rates [172]. Thrombi seen in serious cases of COVID-19 and postmortem in autopsies [5,7,9,10,174,175] can provide only tenuous clues as to whether hemagglutination triggered by SARS-CoV-2 could have initially triggered coagulation, or whether these developed from an inflammatory cascade caused by viral infection [16,174,[176][177][178][179][180].…”

Section: "Catch and Clump" Occlusion Of The Microvasculaturementioning

confidence: 99%

From Cold to Killer: How SARS-CoV-2 Evolved without Hemagglutinin Esterase to Agglutinate and Then Clot Blood Cells

Scheim¹

2022

Preprint

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The role of vascular occlusion in the morbidities, pulmonary and systemic, of COVID-19 has received increasing focus. Histological studies of lung tissue from COVID-19 patients have found extensively damaged endothelium of capillaries adjoining relatively intact alveoli, corresponding to hypoxemia accompanying normal breathing mechanics in such patients.Essential to the study of vascular occlusion in COVID-19 are viral properties dating back to studies of Jonas Salk in the 1940s that have been positively established for SARS-CoV-2. First, SARS-CoV-2 binds to red blood cells (RBCs) in vitro and also clinically in COVID-19 patients. Second, although fusion and replication of SARS-CoV-2 occur via ACE2, such hemagglutinating viruses initially attach to infective targets and clump with blood cells via much more abundantly distributed glycoconjugate binding sites, notably those tipped with sialic acid (SA). SARS-CoV-2, in particular, attaches to these glycan binding sites. Third, certain enveloped viruses express an enzyme, hemagglutinin esterase (HE), that counteracts viral-RBC clumping. Notably, among betacoronaviruses, the common cold strains express HE while SARS-CoV-2, SARS-CoV-1 and MERS, the virulent strains, do not. The hemagglutinating properties of SARS-COV-2 establish a framework for “catch and clump” induction of microvascular occlusion proposed here. Ultramicroscopic studies of tissues from COVID-19 patients indicate a key role for hemagglutination early and mid-course in COVID-19, before such clumps develop into clots via the coagulation cascade.

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Erythrocyte Aggregation as a Determinant of Blood Flow: Effect of pH, Temperature and Osmotic Pressure

Cited by 16 publications

References 7 publications

A Deadly Embrace: Hemagglutination Mediated by SARS-CoV-2 Spike Protein at Its 22 N-Glycosylation Sites, Red Blood Cell Surface Sialoglycoproteins, and Antibody

A Deadly Embrace: Hemagglutination Mediated by SARS-CoV-2 Spike Protein at Its 22 N-Glycosylation Sites, Red Blood Cell Surface Sialoglycoproteins, and Antibody

Erythrocyte Aggregation and Blood Viscosity is Similar in Homozygous Sickle Cell Disease Patients with and without Leg Ulcers

From Cold to Killer: How SARS-CoV-2 Evolved without Hemagglutinin Esterase to Agglutinate and Then Clot Blood Cells

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