Rheological properties of sickle erythrocytes in patients with sickle‐cell anemia: The effect of hydroxyurea, fetal hemoglobin, and α‐thalassemia

Ballas, Samir K.; Connes, Philippe

doi:10.1111/ejh.13173

Cited by 22 publications

(18 citation statements)

References 34 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…At the same time, the blood of patients with rare anemias was investigated ( Clark et al, 1980 ), and as the Technicon ektacytometers were replaced by the second generation Lorrca MaxSis devices produced by RR Mechatronics, scrupulous comparison of the readouts obtained by both types of devices was performed for blood of patients with hereditary hemolytic anemia. ( Da Costa et al, 2016 ; Lazarova et al, 2017 ; Ballas et al, 2018 ; Ciepiela, 2018 ; Llaudet-Planas et al, 2018 ; Zaninoni et al, 2018 ; Kaestner and Bianchi, 2020 ; Zaidi et al, 2020 ; Zama et al, 2020 ). The number of reports on the clinical applications of the device for the assessment of the changes in rheology for human patients is steadily growing.…”

Section: Introductionmentioning

confidence: 99%

Donor Age and Red Cell Age Contribute to the Variance in Lorrca Indices in Healthy Donors for Next Generation Ektacytometry: A Pilot Study

et al. 2021

View full text Add to dashboard Cite

The ability of red blood cells (RBCs) to transport gases, their lifespan as well as their rheological properties invariably depend on the deformability, hydration, and membrane stability of these cells, which can be measured by Laser optical rotational red cell analyser (Lorrca® Maxsis, RR Mechatronics). The osmoscan mode of Lorrca is currently used in diagnosis of rare anemias in clinical laboratories. However, a broad range of normal values for healthy subjects reduces the sensitivity of this method for diagnosis of mild disease phenotype. In this pilot study, we explored the impact of age and gender of 45 healthy donors, as well as RBC age on the Lorrca indices. Whereas gender did not affect the Lorrca indices in our study, the age donors had a profound effect on the O_hyper parameter. To study the impact of RBC age on the osmoscan parameters, we have isolated low (L)-, medium (M)-, or high (H)- density fractions enriched with young, mature, and senescent RBCs, respectively, and evaluated the influence of RBC age-related properties, such as density, morphology, and redox state, on the osmoscan indices. As before, O_hyper was the most sensitive parameter, dropping markedly with an increase in RBC density and age. Senescence was associated with a decrease in deformability (EI_max) and tolerability to low and high osmolatites (Area). L-fraction was enriched with reticulocytes and cells with high projected area and EMA staining, but also contained a small number of cells small in projected area and most likely, terminally senescent. L-fraction was on average slightly less deformable than mature cells. The cells from the L-fraction produced more oxidants and NO than all other fractions. However, RBCs from the L-fraction contained maximal levels of reduced thiols compared to other fractions. Our study suggests that reference values for O_hyper should be age-stratified, and, most probably, corrected for the average RBC age. Further multi-center study is required to validate these suggestions before implementing them into clinical practice.

show abstract

Section: Introductionmentioning

confidence: 99%

Donor Age and Red Cell Age Contribute to the Variance in Lorrca Indices in Healthy Donors for Next Generation Ektacytometry: A Pilot Study

et al. 2021

View full text Add to dashboard Cite

show abstract

“…and probably 0% in the study of Embury et al 8 . We recently showed that patients with fetal Hb (HbF) level of >10% and without α‐thalassaemia had greater RBC deformability than patients with α‐thalassaemia and a HbF level of <10% 13 . Indeed, promoting HbF production through HU therapy in ˜75% of the patients of the present study could have lowered the effects of α‐thalassaemia, although α‐thalassaemia may also influence the HbF level 3 and could explain the discrepancies.…”

Section: Discussionmentioning

confidence: 93%

Comparisons of oxygen gradient ektacytometry parameters between sickle cell patients with or without α‐thalassaemia

et al. 2021

Self Cite

View full text Add to dashboard Cite

Summary The present study tested the impact of α‐thalassaemia on oxygen gradient ektacytometry in sickle cell anaemia (SCA). Three SCA groups were compared: (i) no α‐thalassaemia (four α‐genes, n = 62), (ii) silent α‐thalassaemia (three α‐genes, n = 35) and (iii) homozygous α‐thalassaemia (two α‐genes, n = 12). Red blood cell (RBC) deformability measured in normoxia was not different between the three groups. The lowest RBC deformability reached at low oxygen partial pressure (pO2) was greater and the pO2 at which RBC started to sickle was lower in the two α‐genes group compared to the other groups. Our present study showed an effect of α‐thalassaemia on oxygen gradient ektacytometry in SCA.

show abstract

“…41,42 It also improves RBC deformability. 43 More recently, HU was reported to have antioxidant activity. 44 It appears that patients whose high neutrophil and reticulocyte counts decrease significantly after HU therapy have a higher increase in Hb F levels.…”

Section: Company Mechanism Of Action Indicationmentioning

confidence: 99%

The Evolving Pharmacotherapeutic Landscape for the Treatment of Sickle Cell Disease

Ballas¹

2020

Mediterr J Hematol Infect Dis

View full text Add to dashboard Cite

Sickle cell disease (SCD) is an extremely heterogeneous disease that has been associated with global morbidity and early mortality. More effective and inexpensive therapiesare needed. During the last five years the landscape of the pharmacotherapy of SCD has changed dramatically. Currently, there are at least 50 drugs that have been used or under consideration to use for the treatment of SCD. These fall into 3 categories: the first category includes the three drugs (Hydroxyurea, L-Glutamine and Crizanlizumab tmca) that have been approved by the United States Food and Drug Administration (FDA) based on successful clinical trials. The second category includes 22 drugs that failed, discontinued or terminated for now and the third category includes 25 drugs that are actively being considered for the treatment of SCD. New therapies targeting multiple pathways in its complex pathophysiology have been achieved or are under continued investigation. The emerging trend seems to be the use of multimodal drugs (i.e. drugs that have different mechanisms of action) to treat SCD similar to the use of multiple chemotherapeutic agents to treat cancer.

show abstract

Rheological properties of sickle erythrocytes in patients with sickle‐cell anemia: The effect of hydroxyurea, fetal hemoglobin, and α‐thalassemia

Abstract: Elevated levels of HbF with or without HU and α-thalassemia improve sickle RBC rheology, which, in turn, improve the clinical picture of SCA.

Cited by 22 publications

References 34 publications

Donor Age and Red Cell Age Contribute to the Variance in Lorrca Indices in Healthy Donors for Next Generation Ektacytometry: A Pilot Study

Donor Age and Red Cell Age Contribute to the Variance in Lorrca Indices in Healthy Donors for Next Generation Ektacytometry: A Pilot Study

Comparisons of oxygen gradient ektacytometry parameters between sickle cell patients with or without α‐thalassaemia

The Evolving Pharmacotherapeutic Landscape for the Treatment of Sickle Cell Disease

Contact Info

Product

Resources

About