Sickle cell anemia (SCA) is a genetic condition that alters the conformation of deoxygenated red blood cells, which results in their stiffening and the occurrence of vaso-occlusive crises, endothelium damage, organ dysfunction and systemic complications. Additionally, SCA limits the participation of individuals in physical and social activities. As we consider that physical exercise promotes the recovery of functional capacity and cardiorespiratory conditioning, we aim to verify the patterns of prescription, the effects and safety of exercise for individuals with SCA.

Sickle cell anemia (SCA) is a blood condition that causes severe pain. One of the therapeutic agents used for the treatment of SCA is hydroxyurea, which reduces the episodes of pain but causes DNA damage to white blood cells. The aim of this study was to evaluate the efficacy of the combination of hydroxyurea and iron chelation therapy in relation to the extent of DNA-associated damage. Blood samples were collected from 120 subjects from five groups. Various hematological parameters of the obtained serum were analyzed. The amount of damage caused to their DNA was detected using the comet assay and fluorescent microscopy techniques. The percentage of DNA damage in the group that was subjected to the combination therapy (target group) was 1.32% ± 1.51%, which was significantly lower (P < .05) than that observed in the group treated with hydroxyurea alone (6.36% ± 2.36%). While the target group showed comparable levels of hemoglobin F and lactate dehydrogenase compared to the group that was treated with hydroxyurea alone, highly significant levels of transferrin receptors and ferritin were observed in the target group. The results of this study revealed that the administration of iron chelation drugs with hydroxyurea may help improve patients' health and prevent the DNA damage caused to white blood cells due to hydroxyurea. Further studies are needed to better understand the underlying mechanisms that are involved in this process.

Sickle cell anemia (SCA) is an inherited blood disorder that affects over 300,000 newborns worldwide every year, being particularly prevalent in Sub-Saharan Africa. Despite being a monogenic disease, SCA shows a remarkably high clinical heterogeneity. Several studies have already demonstrated the existence of some polymorphisms that can provide major clinical benefits, producing a mild phenotype. Moreover, the existence of distinct haplotypes can also influence the phenotype patterns of certain populations, leading to different clinical manifestations. Our aim was to assess the association between polymorphisms in genes previously related to SCA disease severity in an Angolan pediatric population.

Sickle cell anemia (SCA) is associated with a hypercoagulable state. Increased platelet activation is reported in SCA and SCA platelets may present augmented adhesion to the vascular endothelium, potentially contributing to the vaso-occlusive process. We sought to observe the effects of platelets (PLTs) from healthy control (CON) individuals and SCA individuals on endothelial activation, in vitro. Human umbilical vein endothelial cells (HUVEC) were cultured, in the presence, or not, of washed PLTs from CON or steady-state SCA individuals. Supernatants were reserved for cytokine quantification, and endothelial adhesion molecules (EAM) were analyzed by flow cytometry; gene expressions of ICAM1 and genes of the NF-κB pathway were analyzed by qPCR. SCA PLTs were found to be more inflammatory, displaying increased adhesive properties, an increased production of IL-1β and a tendency towards elevated expressions of P-selectin and activated αIIbβ3. Following culture in the presence of SCA PLTs, HUVEC presented significant augmentations in the expressions of the EAM, ICAM-1 and E-selectin, as well as increased IL-8 production and increased ICAM1 and NFKB1 (encodes p50 subunit of NF-κB) gene expressions. Interestingly, transwell inserts abolished the effects of SCA PLTs on EAM expression. Furthermore, an inhibitor of the NF-κB pathway, BAY 11-7082, also prevented the induction of EAM expression on the HUVEC surface by SCA PLTs. In conclusion, we find further evidence to indicate that platelets circulate in an activated state in sickle cell disease and are capable of stimulating endothelial cell activation. This effect appears to be mediated by direct contact, or even adhesion, between the platelets and endothelial cells and via NFκB-dependent signaling. As such, activated platelets in SCD may contribute to endothelial activation and, therefore, to the vaso-occlusive process. Results provide further evidence to support the use of anti-platelet approaches in association with other therapies for SCD.

Sickle cell anemia (SCA) is the commonest severe monogenic disorders of humans. The disease has been highly characterized in high-income countries but not in sub-Saharan Africa where SCA is most prevalent. We conducted a retrospective cohort study of all children 0-13 years admitted from within a defined study area to Kilifi County Hospital in Kenya over a five-year period. Children were genotyped for SCA retrospectively and incidence rates calculated with reference to population data. Overall, 576 of 18,873 (3.1%) admissions had SCA of whom the majority (399; 69.3%) were previously undiagnosed. The incidence of all-cause hospital admission was 57.2/100 person years of observation (PYO; 95%CI 52.6-62.1) in children with SCA and 3.7/100 PYO (95%CI 3.7-3.8) in those without SCA (IRR 15.3; 95%CI 14.1-16.6). Rates were higher for the majority of syndromic diagnoses at all ages beyond the neonatal period, being especially high for severe anemia (hemoglobin <50 g/L; IRR 58.8; 95%CI 50.3-68.7), stroke (IRR 486; 95%CI 68.4-3,450), bacteremia (IRR 23.4; 95%CI 17.4-31.4), and for bone (IRR 607; 95%CI 284-1,300), and joint (IRR 80.9; 95%CI 18.1-362) infections. The use of an algorithm based on just five clinical features would have identified approximately half of all SCA cases among hospital-admitted children with a number needed to test to identify each affected patient of only fourteen. Our study illustrates the clinical epidemiology of SCA in a malaria-endemic environment without specific interventions. The targeted testing of hospital-admitted children using the Kilifi Algorithm provides a pragmatic approach to early diagnosis in high-prevalence countries where newborn screening is unavailable.

Patients with sickle cell anemia (SCA) have a high incidence of ischemic stroke, but are usually excluded from thrombolytic therapy due to concerns for cerebral hemorrhage. Maladaptation to cerebral ischemia may also contribute to the stroke propensity in SCA. Here we compared post-stroke cortical collateral circulation in transgenic sickle (SS) mice, bone marrow grafting-derived SS-chimera, and wildtype (AA) controls, because collateral circulation is a critical factor for cell survival within the ischemic penumbra. Further, it has been shown that SS mice develop poorer neo-collateral perfusion after limb ischemia. We used the middle cerebral artery (MCA)-targeted photothrombosis model in this study, since it is better tolerated by SS mice and creates a clear infarct core versus peri-infarct area. Compared to AA mice, SS mice showed enlarged infarction and lesser endothelial proliferation after photothrombosis. SS-chimera showed anemia, hypoxia-induced erythrocyte sickling, and attenuated recovery of blood flow in the ipsilateral cortex after photothrombosis. In AA chimera, cerebral blood flow in the border area between MCA and the anterior cerebral artery (ACA) and posterior cerebral artery (PCA) trees improved from 44% of contralateral level after stroke to 78% at 7 d recovery. In contrast, blood flow in the MCA-ACA and MCA-PCA border areas only increased from 35 to 43% at 7 d post-stroke in SS chimera. These findings suggest deficits of post-stroke collateral circulation in SCA. Better understanding of the underpinnings may suggest novel stroke therapies for SCA patients.

Children with sickle cell anemia (SCA) are at increased risk of acute kidney injury (AKI) that may lead to death or chronic kidney disease. This study evaluated AKI prevalence and risk factors in children with SCA hospitalized with a vaso-occlusive crisis (VOC) in a low-resource setting. Further, we evaluated whether modifications to the Kidney Disease: Improving Global Outcomes (KDIGO) definition would influence clinical outcomes of AKI in children with SCA hospitalized with a VOC.

Sickle cell anemia causes severe complications and premature death. Five common β-globin gene cluster haplotypes are each associated with characteristic fetal hemoglobin (HbF) levels. As HbF is the major modulator of disease severity, classifying patients according to haplotype is useful. The first method of haplotype classification used restriction fragment length polymorphisms (RFLPs) to detect single nucleotide polymorphisms (SNPs) in the β-globin gene cluster. This is labor intensive, and error prone.

Sickle cell anemia (SCA) is a hereditary hemoglobinopathy with a variable phenotype. There is no single biomarker that adequately predicts disease severity and can be used to monitor treatment response in patients in clinical trials and clinical care. The use of clinical outcomes, such as vaso-occlusive crises (VOC), requires long and expensive studies, sometimes with inconclusive results. To address these limitations, there are several biomarkers under study to improve the ability to predict complications and assess treatment response in both clinical and research settings. Oxygen gradient ektacytometry, also called as oxygenscan, is an assay that measures the effects of deoxygenation and reoxygenation on red blood cell (RBC) deformability and is gaining popularity in SCA research, because it captures the dynamic sickling capacity of a patient's RBCs as they are subjected to an oxygen gradient under steady shear stress. We describe here the oxygenscan methodology and evaluate the correlation between oxygenscan parameters and more well-known biomarkers of SCA such as fetal hemoglobin (HbF), F-cells, and dense red blood cells (DRBCs). Our data indicate that the oxygenscan curve is affected by all these parameters and the result incorporates the effects of %HbF, %F-cells, RBC hydration, and RBC membrane deformability.

Sickle cell disease (SCD) is a chronic blood disorder that is often associated with acute and chronic cerebrovascular complications, including strokes and impaired cognition. Using functional resting state magnetic resonance images, we performed whole-brain analysis of the amplitude of low frequency fluctuations (ALFF), to detect areas of spontaneous blood oxygenation level dependent signal across brain regions. We compared the ALFF of 20 SCD patients to that observed in 19 healthy, age and ethnicity-matched, control subjects. Significant differences were found in several brain regions, including the insula, precuneus, anterior cingulate cortex and medial superior frontal gyrus. To identify the ALFF differences resulting from anemia alone, we also compared the ALFF of SCD patients to that observed in 12 patients having comparable hemoglobin levels but lacking sickle hemoglobin. Increased ALFF in the orbitofrontal cortex and the anterior and posterior cingulate cortex and decreased ALFF in the frontal pole, cerebellum and medial superior frontal gyrus persisted after accounting for the effect of anemia. The presence of white matter hyperintensities was associated with depressed frontal and medial superior frontal gyri activity in the SCD subjects. Decreased ALFF in the frontal lobe was correlated with decreased verbal fluency and cognitive flexibility. These findings may lead to a better understanding of the pathophysiology of SCD.

Background: Children with sickle cell disease (SCD) often suffer from growth deficits and impaired immunity. However, the association between mild to moderate malnutrition and in vitro lymphocyte function has not been well studied. The goal of this study was to investigate the effects of undernutrition on lymphocyte functions in children with SCD. Methods: Weight; height; plasma concentrations of albumin (Alb), prealbumin (PA), transferrin (Tf), retinol-binding protein (RBP), α1-acid glycoprotein (AGP), C-reactive protein (CRP), and ceruloplasmin (Cp); and lymphocyte proliferation and interleukin (IL)-2 in phytohemagglutinin-treated blood lymphocytes were measured in 90 children with SCD (59 SS, 4 Sβ°, 27 SC hemoglobin genotypes). Results: The mean age of the children included in the analysis was 7.65 years. Four of the 90 children had weight and height below the fifth percentile. A higher percentage of children with HbSS/HbSβ° (61.4%) than of those with HbSC (44%) had ≥2 plasma protein concentrations below normal (Alb <35 g/L, PA <160 mg/L, Tf <2.0 g/L, and RBP ≤20 mg/L). Mean anthropometric measurements, hemoglobin, and hematocrit were lower in children with HbSS/HbSβ° than in those with HbSC (P<0.05). Lymphocyte proliferation was reduced by 20% to 27% in children with HbSS/HbSβ° with undernutrition plus inflammation (AGP >1 g/L, CRP >5 mg/L, Cp >600 mg/L) compared to children with neither. Regardless of inflammatory status, lymphocyte proliferation was reduced by 29% to 49% in children with HbSS/HbSβ° and undernutrition defined by PA or Alb plus RBP (P<0.05) compared to those with RBP within normal range. Neither undernutrition nor inflammation reduced lymphocyte proliferation in children with HbSC. Mean IL-2 activity was reduced by undernutrition, defined as PA <160 mg/L, in both groups. PA, RBP, and hemoglobin concentrations positively correlated with in vitro lymphocyte functions (P<0.05). Conclusion: Undernutrition altered in vitro lymphocyte function in children with the HbSS/HbSβ° genotypes. Dietary supplements may improve the altered functions in these children.

Sickle cell anemia (SCA) is a monogenic disease of high mortality, affecting millions of people worldwide. There is no broad, effective, and safe definitive treatment for SCA, so the palliative treatments are the most used. The establishment of an in vitro model allows better understanding of how the disease occurs, besides allowing the development of more effective tests and treatments. In this context, iPSC technology is a powerful tool for basic research and disease modeling, and a promise for finding and screening more effective and safe drugs, besides the possibility of use in regenerative medicine. This work obtained a model for study and treatment of SCA using iPSC. Then, episomal vectors were used for reprogramming peripheral blood mononuclear cells to obtain integration-free iPSC. Cells were collected from patients treated with hydroxyurea and without treatment. The iPSCP Bscd lines were characterized for pluripotent and differentiation potential. The iPSC lines were differentiated into HSC, so that we obtained a dynamic and efficient protocol of CD34+CD45+ cells production. We offer a valuable tool for a better understanding of how SCA occurs, in addition to making possible the development of more effective drugs and treatments and providing better understanding of widely used treatments, such as hydroxyurea.

Sickle cell disease is a hereditary disorder characterized by haematological anaemia. Several studies assumed that adult sickle patients might develop metabolic syndrome features as hyperglycaemia, hypertension and dyslipidaemia. The aim of this study was to evaluate the metabolic syndrome risk factors among adult Sudanese with sickle cell anemia in the steady state.

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.

Plasmodium falciparum malaria causes morbidity and mortality in African children with sickle cell anemia (SCA), but comparisons of host responses to P falciparum between children with SCA (homozygous sickle cell disease/hemoglobin SS [HbSS]) and normal hemoglobin genotype/hemoglobin AA (HbAA) are limited. We assessed parasite biomass and plasma markers of inflammation and endothelial activation in children with HbAA (n = 208) or HbSS (n = 22) who presented with severe anemia and P falciparum parasitemia to Mulago Hospital in Kampala, Uganda. Genotyping was performed at study completion. No child had known SCA at enrollment. Children with HbSS did not differ from children with HbAA in peripheral parasite density, but had significantly lower sequestered parasite biomass. Children with HbSS had greater leukocytosis but significantly lower concentrations of several plasma inflammatory cytokines, including tumor necrosis factor α (TNF-α). In contrast, children with HbSS had threefold greater concentrations of angiopoietin-2 (Angpt-2), a marker of endothelial dysregulation associated with mortality in severe malaria. Lower TNF-α concentrations were associated with increased risk of postdischarge mortality or readmission, whereas higher Angpt-2 concentrations were associated with increased risk of recurrent clinical malaria. Children with SCA have decreased parasite sequestration and inflammation but increased endothelial dysregulation during severe anemia with P falciparum parasitemia, which may ameliorate acute infectious complications but predispose to harmful long-term sequelae.

Allogeneic hematopoietic stem cell transplantation (HSCT) is the only curative treatment for sickle cell anemia (SCA). We report our experience with transplantation in children with the Black African variant of SCA and the effects of transplant on erythroid compartment in bone marrow (BM).

Human parvovirus B19 is the etiologic agent of erythema infectiosum in children. It is also associated with other clinical manifestations in different target groups. Patients with chronic hemolytic anemia are at high risk of developing acute erythroblastopenia following infection by the virus. They usually become highly viremic and pose an increased risk of virus transmission. Close monitoring of such high risk groups is required for epidemiologic surveillance and disease prevention activities. Here we report a molecular epidemiological study on B19 virus infection in Tunisian patients with chronic hemolytic anemia.

Sickle cell anemia (SCA) is a genetic and hemolytic disease globally characterized by social vulnerability. Food consumption has been insufficiently analyzed in SCA. Secondary iron overload is often observed. This leads to unreliable recommendations for dietary iron restriction. We assessed food consumption and iron intake among adults with SCA. Considering the guidelines for healthy eating, foods were grouped according to the NOVA classification. This transversal study included 74.4% of eligible patients who were registered in the reference center for SCA treatment in Rio de Janeiro, Brazil, in 2019. Data on food consumption were collected through 24 h recall. The monthly household income of 82.3% of patients was less than $770. The consumption of fresh or minimally processed foods was directly associated with monthly household income (p < 0.0001; η2 = 0.87). Ultra-processed foods provided more than one-third of the total energy intake (35.2%). The prevalence of inadequate iron intake was about 40% among women, while that of iron intake above the tolerable upper limit was 0.8%. People from lower socioeconomic classes had the lowest iron intake. Strategies to encourage the consumption of fresh or minimally processed foods are needed considering the requirement of an antioxidant diet in SCA. These findings highlight the need for health equity to ensure food security and healthy eating in SCA.

Fetal hemoglobin (HbF) is an important modulator of sickle cell disease (SCD). HbF has previously been shown to be affected by variants at three loci on chromosomes 2, 6 and 11, but it is likely that additional loci remain to be discovered.

Prior studies have described high venous signal qualitatively using arterial spin labelling (ASL) in patients with sickle cell anemia (SCA), consistent with arteriovenous shunting. We aimed to quantify the effect and explored cross-sectional associations with arterial oxygen content (CaO2), disease-modifying treatments, silent cerebral infarction (SCI), and cognitive performance. 94 patients with SCA and 42 controls underwent cognitive assessment and MRI with single- and multi- inflow time (TI) ASL sequences. Cerebral blood flow (CBF) and bolus arrival time (BAT) were examined across gray and white matter and high-signal regions of the sagittal sinus. Across gray and white matter, increases in CBF and reductions in BAT were observed in association with reduced CaO2 in patients, irrespective of sequence. Across high-signal sagittal sinus regions, CBF was also increased in association with reduced CaO2 using both sequences. However, BAT was increased rather than reduced in patients across these regions, with no association with CaO2. Using the multiTI sequence in patients, increases in CBF across white matter and high-signal sagittal sinus regions were associated with poorer cognitive performance. These novel findings highlight the utility of multiTI ASL in illuminating, and identifying objectively quantifiable and functionally significant markers of, regional hemodynamic stress in patients with SCA.