Decrease of externalized phosphatidylserine density on red blood cell‐derived microparticles in SCA patients treated with hydroxycarbamide

Garnier, Yohann; Ferdinand, Séverine; Connes, Philippe; Garnier, M; Etienne‐Julan, Maryse; Lemonne, Nathalie; Romana, Marc

doi:10.1111/bjh.14810

Cited by 8 publications

(8 citation statements)

References 10 publications

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“…These conflicting results could be accounted for by the large interindividual variation in MPs concentration in SCD. However, a longitudinal study reported no change in MPs concentration in patients receiving HU for 24 months [ 134 ]. To further characterize the biomarker status of MPs, an observational study with an estimated enrollment of 360 participants has also been initiated (NCT012422878).…”

Section: Pathophysiology Of Scdmentioning

confidence: 99%

“…Our group reported that SCA patients with frequent VOCs had increased levels of PLT-MPs, compared to SCA patients with rare crises [ 141 ]. In SCA patients, we showed using two longitudinal cohorts, that circulating PLT- and RBC-MPs PS exposure level was increased during VOC, but decreased after two years under HU treatment, when compared to steady-state conditions [ 39 , 134 , 140 ]. Therefore, PS exposure by these MPs subtypes seems to be a promising marker of clinical severity and of HU treatment efficacy.…”

Section: Pathophysiology Of Scdmentioning

confidence: 99%

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Extracellular Vesicles in Sickle Cell Disease: A Promising Tool

et al. 2022

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Sickle cell disease (SCD) is the most common hemoglobinopathy worldwide. It is characterized by an impairment of shear stress-mediated vasodilation, a pro-coagulant, and a pro-adhesive state orchestrated among others by the depletion of the vasodilator nitric oxide, by the increased phosphatidylserine exposure and tissue factor expression, and by the increased interactions of erythrocytes with endothelial cells that mediate the overexpression of adhesion molecules such as VCAM-1, respectively. Extracellular vesicles (EVs) have been shown to be novel actors involved in SCD pathophysiological processes. Medium-sized EVs, also called microparticles, which exhibit increased plasma levels in this pathology, were shown to induce the activation of endothelial cells, thereby increasing neutrophil adhesion, a key process potentially leading to the main complication associated with SCD, vaso-occlusive crises (VOCs). Small-sized EVs, also named exosomes, which have also been reported to be overrepresented in SCD, were shown to potentiate interactions between erythrocytes and platelets, and to trigger endothelial monolayer disruption, two processes also known to favor the occurrence of VOCs. In this review we provide an overview of the current knowledge about EVs concentration and role in SCD.

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Section: Pathophysiology Of Scdmentioning

confidence: 99%

Section: Pathophysiology Of Scdmentioning

confidence: 99%

Extracellular Vesicles in Sickle Cell Disease: A Promising Tool

et al. 2022

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“…HU improved blood rheology: increased Hct without any increase in blood viscosity and increased RBC deformability Another positive effect of HU treatment is that it reduces PS density on RBC MPs HU also contributes to reduce circulating cell adhesiveness.…”

Section: Therapiesmentioning

confidence: 99%

Insight into the complex pathophysiology of sickle cell anaemia and possible treatment

Piccin

Murphy

Eakins

et al. 2019

European J of Haematology

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Sickle cell anaemia (SCA) is the consequence of abnormal haemoglobin production due to an inherited point mutation in the β‐globin gene. The resulting haemoglobin tetramer is poorly soluble when deoxygenated, and when this is prolonged, intracellular gelation of sickle haemoglobin occurs, followed by haemoglobin polymerisation. If many cycles of sickling and unsickling occur, the red cell membrane will be disrupted leading to haemolysis and vaso‐occlusive events. Recent studies have also shown that leucocyte adhesion molecules and nitric oxide (NO) depletion are involved in endothelial damage. New insights in SCA pathophysiology and vascular biology have shown that cell‐derived microparticle (MP) generation is also involved in the vaso‐occlusion. Endothelial damage is perpetuated by impaired production or increased consumption of protective modulators such as protein C, protein S and NO. New therapeutic interventions should address these aspects of SCA pathogenesis. To date, the only US‐FDA‐approved therapy to prevent painful vaso‐occulsive episodes is hydroxyurea that reduces haemoglobin polymerisation in sickle cells by increasing the production of foetal haemoglobin and L‐glutamine. However, several new drugs have been tested in the last years in randomised clinical trials. We here report an update on the current status of knowledge on SCA.

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“…While pre-incubation of m/lEVs with annexin-V, a PS blocker, abolished the induced endothelial ICAM-1 overexpression, we have shown that the proinflammatory properties of m/lEVs collected during a vaso-occlusive crisis, a condition associated with high PS externalization of m/lEVs ( 114 ), were exacerbated. In contrast, these proinflammatory properties were considerably reduced for m/lEVs obtained from patients treated with HU, which exhibited low PS externalization ( 116 ). In addition, we presented evidence that the endothelial activation mediated by these EVs also involved TLR4 signaling pathway ( 125 ).…”

Section: Extracellular Vesicles As Bio-effectors Of Scdmentioning

confidence: 99%

“…Knowing the wide distribution of m/lEV concentration in SCA patients ( 103 , 112 , 113 ), these contradictory results could be related to the cross-sectional design of these studies. In order to reduce the inter variability, we have implemented a longitudinal follow-up of SCA patients before and after 2 years of HU treatment ( 116 ). While no change in m/lEV concentration was detected, two qualitative parameters of m/lEVs originated from RBCs were modified during the course of HU treatment: EVs size was increased and their PS exposure was decreased.…”

Section: Extracellular Vesicles In Scdmentioning

confidence: 99%

Extracellular Vesicles in Sickle Cell Disease: Plasma Concentration, Blood Cell Types Origin Distribution and Biological Properties

et al. 2021

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Prototype of monogenic disorder, sickle cell disease (SCD) is caused by a unique single mutation in the β-globin gene, leading to the production of the abnormal hemoglobin S (HbS). HbS polymerization in deoxygenated condition induces the sickling of red blood cells (RBCs), which become less deformable and more fragile, and thus prone to lysis. In addition to anemia, SCD patients may exhibit a plethora of clinical manifestations ranging from acute complications such as the frequent and debilitating painful vaso-occlusive crisis to chronic end organ damages. Several interrelated pathophysiological processes have been described, including impaired blood rheology, increased blood cell adhesion, coagulation, inflammation and enhanced oxidative stress among others. During the last two decades, it has been shown that extracellular vesicles (EVs), defined as cell-derived anucleated particles delimited by a lipid bilayer, and comprising small EVs (sEVs) and medium/large EVs (m/lEVs); are not only biomarkers but also subcellular actors in SCD pathophysiology. Plasma concentration of m/lEVs, originated mainly from RBCs and platelets (PLTs) but also from the other blood cell types, is higher in SCD patients than in healthy controls. The concentration and the density of externalized phosphatidylserine of those released from RBCs may vary according to clinical status (crisis vs. steady state) and treatment (hydroxyurea). Besides their procoagulant properties initially described, RBC-m/lEVs may promote inflammation through their effects on monocytes/macrophages and endothelial cells. Although less intensely studied, sEVs plasma concentration is increased in SCD and these EVs may cause endothelial damages. In addition, sEVs released from activated PLTs trigger PLT-neutrophil aggregation involved in lung vaso-occlusion in sickle mice. Altogether, these data clearly indicate that EVs are both biomarkers and bio-effectors in SCD, which deserve further studies.

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Decrease of externalized phosphatidylserine density on red blood cell‐derived microparticles in SCA patients treated with hydroxycarbamide

Abstract: 7.4 (6.9-8.0) 7.6 (7.0-8.5)** 7.9 (6.85-9.1)* 7.6 (7.4-8.7)** 7.7 (7.2-8.2)

Cited by 8 publications

References 10 publications

Extracellular Vesicles in Sickle Cell Disease: A Promising Tool

Extracellular Vesicles in Sickle Cell Disease: A Promising Tool

Insight into the complex pathophysiology of sickle cell anaemia and possible treatment

Extracellular Vesicles in Sickle Cell Disease: Plasma Concentration, Blood Cell Types Origin Distribution and Biological Properties

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