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

Abstract

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.

Circulating megakaryocyte and platelet microvesicles correlate with response to ruxolitinib and distinct disease severity in patients with myelofibrosis

“…Although carefully checked, the limited number of patients available for adhesion experiments might not be representative of the whole cohort (Hierso et al, 2017). However, given our observation that RBC adhesion to endothelial cells is related to reticulocytes at basal state in our patients, as previously reported for human reticulocytes in an ex vivo rat model , one interesting finding is that adhesion preferentially involved ISCs during VOC, indicating that the adhesion phenomenon might involve different RBC sub-populations during crisis.…”

“…). The present study compared blood rheology, the percentage of irreversibly sickled cells (%ISCs) with innovative technology, and RBC adhesion in the same patients at steady state and during acute VOC.The study included 32 adult SCA patients [12 females/20 males, median age 27 years; interquartile range (IQR): 18-38 years] regularly followed by the Sickle Cell Centre in Guadeloupe and admitted to the emergency department for painful VOC(Hierso et al, 2017). Blood was sampled upon…”

Targeting βCys93 in hemoglobin S with an antisickling agent possessing dual allosteric and antioxidant effects

“…A recent perspective study, in which 32 sickle patients were monitored during vaso-occlusive crisis showed exacerbated oxidative stress including the accumulation of harmful RBC-derived microparticles (MPs) (27). Circulating MPs were shown recently to deliver heme to the vascular system initiating inflammatory responses in a sickle mouse model (28).…”

New insights into red cell rheology and adhesion in patients with sickle cell anaemia during vaso‐occlusive crises

“…The study included 32 adult SCA patients [12 females/20 males, median age 27 years; interquartile range (IQR): 18–38 years] regularly followed by the Sickle Cell Centre in Guadeloupe and admitted to the emergency department for painful VOC (Hierso et al , ). Blood was sampled upon admission to the emergency department for a VOC episode and before any treatment/medication was initiated.…”

“…Although carefully checked, the limited number of patients available for adhesion experiments might not be representative of the whole cohort (Hierso et al , ). However, given our observation that RBC adhesion to endothelial cells is related to reticulocytes at basal state in our patients, as previously reported for human reticulocytes in an ex vivo rat model (Kaul et al , ), one interesting finding is that adhesion preferentially involved ISCs during VOC, indicating that the adhesion phenomenon might involve different RBC sub‐populations during crisis.…”