Red blood cells microparticles are associated with hemolysis markers and may contribute to clinical events among sickle cell disease patients

Olatunya, Oladele Simeon; Lanaro, Carolina; Longhini, Ana Leda; Penteado, Carla Fernanda Franco; Fertrin, Kleber Yotsumoto; Adekile, Adekunle; Saad, Sara T. Olalla; Costa, Fernando Ferreira

doi:10.1007/s00277-019-03792-x

Cited by 32 publications

(38 citation statements)

References 40 publications

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“…The consensus of many studies is that the abundance of circulating microparticles is increased in individuals with SCD as compared with normal subjects, but the abundance is not consistently altered in association with pain crises (Nebor et al, 2014;Hebbel and Key, 2016). Microparticle levels are increased in association with hemolysis (Westerman et al, 2008;van Beers et al, 2009;Merle et al, 2018;Olatunya et al, 2019). It is unclear whether levels of microparticles (either total or those from a specific cell type) are useful biomarkers for disease severity or complications (Hebbel and Key, 2016).…”

Section: Medium-sized Extracellular Vesicles (Microparticles) In Sickmentioning

confidence: 99%

Circulating Extracellular Vesicles and Endothelial Damage in Sickle Cell Disease

et al. 2020

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Endothelial damage is central to the pathogenesis of many of the complications of sickle cell disease. Circulating extracellular vesicles (EVs) have been implicated in modulating endothelial behavior in a variety of different, diseases with vascular pathologies. As seen in other hemolytic diseases, the plasma of sickle cell patients contains EVs of different sizes and cellular sources. The medium-sized vesicles (microparticles) primarily derive from mature red blood cells and platelets; some of these EVs have procoagulant properties, while others stimulate inflammation or endothelial adhesiveness. Most of the small EVs (including exosomes) derive from erythrocytes and erythrocyte precursors, but some also originate from platelets, white blood cells, and endothelial cells. These small EVs may alter the behavior of target cells by delivering cargo including proteins and nucleic acids. Studies in model systems implicate small EVs in promoting vaso-occlusion and disruption of endothelial integrity. Thus, both medium and small EVs may contribute to the increased endothelial damage in sickle cell disease. Development of a detailed understanding of the composition and roles of circulating EVs represents a promising approach toward novel predictive diagnostics and therapeutic approaches in sickle cell disease.

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Section: Medium-sized Extracellular Vesicles (Microparticles) In Sickmentioning

confidence: 99%

Circulating Extracellular Vesicles and Endothelial Damage in Sickle Cell Disease

et al. 2020

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“…In SCD, the substantial hemolysis does not allow Hp and Hpx to complete binding with Hb and heme, respectively, becoming rapidly overwhelmed [134,148]. Both the Hp and Hpx blood concentration was decreased in adult [66,118,121,149] as well as in pediatric SCD patients [150]. The depletion of the Hp and Hpx concentration has been reported to favor the thrombo-inflammation in the vasculature through a mechanism involving the component C5-dependent complement activation [149], which also positively correlated with the percentage of dense sickle cells [151].…”

Section: Antioxidant Defenses In Scdmentioning

confidence: 99%

“…It is an important candidate to participate in RBC-vascular endothelium interaction. Blebs and microparticles (MPs) containing HbS-derived oxidation products, such as metHb, heme and its derived oxidation products (hemin) as well as free iron, accumulate in the and are then released in the vasculature from RBCs(Figure 1) membrane[65,66]. This event produces three significant consequences: i) inhibition of the adherence of sickle cells to endothelium; ii) occurring of binding sites for natural band 3 antibodies (IgG class) that are able to react with the complement system; and iii) boosting of increase oxidative stress and vasculopathy associated to SCD.…”

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confidence: 99%

Sickle Cell Disease: Role of Oxidative Stress and Antioxidant Therapy

Vona¹,

Sposi²,

Mattia³

et al. 2020

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Sickle cell disease (SCD) is the most common hereditary disorder of hemoglobin (Hb) that affects approximately a millions people worldwide. It is characterized by a single nucleotide substitution on the β-globin gene, leading to the production of abnormal sickle hemoglobin with multi-system consequences. Mutated Hb leads to profound changes in: i) red blood cell metabolism and physiology; ii) endothelial signaling; and iii) immune response. Oxidative stress is an important hallmark of SCD. It plays a key role in the pathophysiology of hemolysis, vessel occlusion and the following organ damage in sickle cell patients. For this reason, reactive oxidizing species and the (end)-products of their oxidative reactions have been proposed as markers of both tissue pro-oxidant status and disease severity. Although more studies are needed to clarify their role, antioxidant agents have been shown to be effective in reducing pathological consequences of the disease by preventing oxidative damage in SCD, i.e. by decreasing the oxidant formation or repairing the induced damage. An improved understanding of oxidative stress will lead to targeted antioxidant therapies that should prevent or delay the development of organ complications in this patient population.

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“…As a result of haemolysis, several intracellular and membranous products of red blood cells are released which interact with other molecules to produce many downstream events. 4,5,[20][21][22][23][24][25] Despite the huge advancements provided by both genetic and haemolytic factors in understanding the various processes responsible for the observed clinical variability in SCD, a large knowledge gap still exists regarding the impact of other factors. The situation is more appalling for sub-Saharan Africa, where the bulk of SCD resides, as none of the SCD modifiers have been well studied.…”

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confidence: 99%

“…Despite the low proportion of intravascular haemolysis (approximately ≤30% of total haemolysis in SCD), several studies have associated intensity of haemolysis and its various consequences with some pathogenic processes and clinical phenotypes/complications in patients with SCD. As a result of haemolysis, several intracellular and membranous products of red blood cells are released which interact with other molecules to produce many downstream events 4,5,20‐25 . Despite the huge advancements provided by both genetic and haemolytic factors in understanding the various processes responsible for the observed clinical variability in SCD, a large knowledge gap still exists regarding the impact of other factors.…”

mentioning

confidence: 99%