Plasma Concentration of Platelet-Derived Microparticles Is Related to Painful Vaso-Occlusive Phenotype Severity in Sickle Cell Anemia

Nebor, Danitza; Bowers, Andre; Connes, Philippe; Hardy‐Dessources, Marie‐Dominique; Knight‐Madden, Jennifer; Cumming, Vanessa; Reid, Marvin; Romana, Marc

doi:10.1371/journal.pone.0087243

Cited by 38 publications

(48 citation statements)

References 24 publications

(40 reference statements)

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“…MPs were isolated from plasma by ultracentrifugation as previously described, within 2 h of blood collection, and were stored at −80°C until used (Nieuwland et al , ; Nebor et al , ). MP analysis by flow cytometry was performed using a FC500 flow cytometer (Beckman Coulter, CA, USA) (Nebor et al , , ). The concentration of haem associated with MPs was also quantified using the Quantichrome Haem Assay Kit (Bioassay Systems, Paris, France), after resuspension of MPs in the same volume of buffer (10 mmol/l HEPES pH 7·4, 136 mmol/l NaCl, 5 mmol/l KCl, 2 mmol/l MgCl 2 ) as the plasma volume from which they had been isolated.…”

Section: Methodsmentioning

confidence: 99%

Exacerbation of oxidative stress during sickle vaso‐occlusive crisis is associated with decreased anti‐band 3 autoantibodies rate and increased red blood cell‐derived microparticle level: a prospective study

et al. 2016

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Painful vaso-occlusive crisis, a hallmark of sickle cell anaemia, results from complex, incompletely understood mechanisms. Red blood cell (RBC) damage caused by continuous endogenous and exogenous oxidative stress may precipitate the occurrence of vaso-occlusive crises. In order to gain insight into the relevance of oxidative stress in vaso-occlusive crisis occurrence, we prospectively compared the expression levels of various oxidative markers in 32 adults with sickle cell anaemia during vaso-occlusive crisis and steady-state conditions. Compared to steady-state condition, plasma levels of free haem, advanced oxidation protein products and myeloperoxidase, RBC caspase-3 activity, as well as the concentrations of total, neutrophil- and RBC-derived microparticles were increased during vaso-occlusive crises, whereas the reduced glutathione content was decreased in RBCs. In addition, natural anti-band 3 autoantibodies levels decreased during crisis and were negatively correlated with the rise in plasma advanced oxidation protein products and RBC caspase-3 activity. These data showed an exacerbation of the oxidative stress during vaso-occlusive crises in sickle cell anaemia patients and strongly suggest that the higher concentration of harmful circulating RBC-derived microparticles and the reduced anti-band 3 autoantibodies levels may be both related to the recruitment of oxidized band 3 into membrane aggregates.

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Section: Methodsmentioning

confidence: 99%

Exacerbation of oxidative stress during sickle vaso‐occlusive crisis is associated with decreased anti‐band 3 autoantibodies rate and increased red blood cell‐derived microparticle level: a prospective study

et al. 2016

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“…There are inconsistent data regarding further increases of the concentration of total microparticles during acute painful episodes (38,88)(86,87). A history of at least 3 painful episodes in the previous year was associated with a higher “steady state” plasma concentration of monocyte-derived microparticles in a group of adults with HbSS and HbSβ-thalassemia (91), while another study of adult HbSS patients reported associations of painful episodes in the previous 2 years with lower concentrations of erythrocyte-derived microparticles, but higher total and platelet-derived microparticles (92). …”

Section: Hemostatic Alterations Of Scdmentioning

confidence: 99%

Coagulation abnormalities of sickle cell disease: Relationship with clinical outcomes and the effect of disease modifying therapies

2016

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Sickle cell disease (SCD) is a hypercoagulable state. Patients exhibit increased platelet activation, high plasma levels of markers of thrombin generation, depletion of natural anticoagulant proteins, abnormal activation of the fibrinolytic system, and increased tissue factor expression, even in the non-crisis “steady state.” Furthermore, SCD is characterized by an increased risk of thrombotic complications. The pathogenesis of coagulation activation in SCD appears to be multi-factorial, with contributions from ischemia-reperfusion injury and inflammation, hemolysis and nitric oxide deficiency, and increased sickle RBC phosphatidylserine expression. Recent studies in animal models suggest that activation of coagulation may contribute to the pathogenesis of SCD, but the data on the contribution of coagulation and platelet activation to SCD-related complications in humans are limited. Clinical trials of new generations of anticoagulants and antiplatelet agents, using a variety of clinical endpoints are warranted.

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“…Indeed, it has been shown that MPs originated from sickle RBCs may trigger coagulation, increase the production the production of radical oxygen species by endothelial cells, induce erythrocyte adhesion to endothelial cells and endothelial cell apopotosis, as well as, trigger renal vaso-occlusive crisis in a sickle mouse model [24–26]. Furthermore, several studies also supported a role of MPs in the occurrence of several complications in patients with SCA [15,27–28]. While these data strongly suggest that MPs are not only bio-markers but also bio-effectors in SCA, no study looked at the presence and/or at the circulating MP profile in HbSC patients.…”

Section: Introductionmentioning

confidence: 99%

Differences of microparticle patterns between sickle cell anemia and hemoglobin SC patients

et al. 2017

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Sickle cell anemia (SCA) and hemoglobin SC (HbSC) disease are the two most common forms of sickle cell disease (SCD), a frequent hemoglobinopathy which exhibits a highly variable clinical course. Although high levels of microparticles (MPs) have been consistently reported in SCA and evidence of their harmful impact on the SCA complication occurrences have been provided, no data on MP pattern in HbSC patients has been reported so far. In this study, we determined and compared the MP patterns of 84 HbSC and 96 SCA children, all at steady-state, using flow cytometry. Most of circulating MPs were derived from platelets (PLTs) and red blood cells (RBCs) in the two SCD syndromes. Moreover, we showed that HbSC patients exhibited lower blood concentration of total MPs compared to SCA patients, resulting mainly from a decrease of MP levels originated from RBCs and to a lesser extent from PLTs. We did not detect any association between blood MP concentrations and the occurrence of painful vaso-occlusive crises, acute chest syndrome and pulmonary hypertension in both patient groups. We also demonstrated for the first time, that whatever the considered genotype, RBC-derived MPs exhibited higher externalized phosphatidylserine level and were larger than PLT-derived MPs.

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Plasma Concentration of Platelet-Derived Microparticles Is Related to Painful Vaso-Occlusive Phenotype Severity in Sickle Cell Anemia

Cited by 38 publications

References 24 publications

Exacerbation of oxidative stress during sickle vaso‐occlusive crisis is associated with decreased anti‐band 3 autoantibodies rate and increased red blood cell‐derived microparticle level: a prospective study

Exacerbation of oxidative stress during sickle vaso‐occlusive crisis is associated with decreased anti‐band 3 autoantibodies rate and increased red blood cell‐derived microparticle level: a prospective study

Coagulation abnormalities of sickle cell disease: Relationship with clinical outcomes and the effect of disease modifying therapies

Differences of microparticle patterns between sickle cell anemia and hemoglobin SC patients

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