Sickle cell disease (SCD) is a group of inherited genetic disorders that is caused by a mutation in the gene that codes for hemoglobin subunit β. This systematic review aimed to evaluate the effect of folic acid in the treatment of SCD patients. We retrieved 3730 articles from PubMed, PubMed Central, Google Scholar, and ScienceDirect databases. We employed a search technique that involved framing keywords, such as folic acid, folate, and sickle cell illness, and the Medical Subject Headings (MeSH) strategy in PubMed. We chose research articles that had been published during the last 10 years, as well as case reports, systematic reviews and meta-analyses, literature reviews, randomized controlled trials, and observational studies. Exclusion criteria included paid full-text articles, abstracts, non-English studies, and patients who do not have SCD. The 2020 Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) criteria were used in the design of our systematic review. It was found that the majority of SCD patients were receiving regular folic acid supplements and that their plasma folate levels were either increased or within normal range, with no discernible impact on other clinical outcomes such as hemoglobin levels, infections, or pain crises. SCD patients produce more red blood cells than healthy individuals, and nearly all SCD patients receive daily folic acid supplements. On the other hand, not enough information is available on folic acid\'s potential benefits in the management of SCD; thus, there is a need for more large clinical trials.

Sickle cell anemia (SCA) is the most common cause of stroke in children. As it is a rare disease, studies investigating the association with complications like stroke in SCD have small sample sizes. Here, we performed a systematic review and meta-analysis of the studies exploring an association of genetic variants with stroke to get a better indication of their association with stroke. PubMed and Google Scholar were searched to identify studies that had performed an association analysis of genetic variants for the risk of stroke in SCA patients. After screening of eligible studies, summary statistics of association analysis with stroke and other general information were extracted. Meta-analysis was performed using the fixed effect method on the tool METAL and forest plots were plotted using the R program. The random effect model was performed as a sensitivity analysis for loci where significant heterogeneity was observed. 407 studies were identified using the search term and after screening 37 studies that cumulatively analyzed 11,373 SCA patients were included. These 37 studies included a total of 2,222 SCA patients with stroke, predominantly included individuals of African ancestry (N = 16). Three of these studies performed whole exome sequencing while 35 performed single nucleotide-based genotyping. Though the studies reported association with 132 loci, meta-analyses could be performed only for 12 loci that had data from two or more studies. After meta-analysis we observed that four loci were significantly associated with risk for stroke: -α3.7 kb Alpha-thalassemia deletion (P = 0.00000027), rs489347-TEK (P = 0.00081), rs2238432-ADCY9 (P = 0.00085), rs11853426-ANXA2 (P = 0.0034), and rs1800629-TNF (P = 0.0003396). Ethnic representation of regions with a high prevalence of SCD like the Mediterranean basin and India needs to be improved for genetic studies on associated complications like stroke. Larger genome-wide collaborative studies on SCD and associated complications including stroke need to be performed.

This comprehensive review explores the complex dynamics of nosocomial infections in individuals with sickle cell anemia (SCA) and advocates for a collaborative strategy to enhance prevention. SCA patients, marked by compromised immunity and susceptibility to infections, face unique challenges that necessitate tailored preventive measures. The review underscores the importance of vaccination, antibiotic prophylaxis, education, and environmental hygiene in mitigating the risk of nosocomial infections. Addressing socioeconomic factors, healthcare system limitations, patient-related issues, and cultural considerations is imperative for effective prevention. The call to action emphasizes the pivotal roles of healthcare professionals, policymakers, researchers, and community engagement in implementing targeted interventions. By fostering a collective effort, this review envisions an improved landscape for infection prevention in SCA patients, enhancing their overall health outcomes and quality of life.

Red cell exchanges (RCE) help in the treatment of complications of sickle cell anemia (SCA) by reducing the viscosity of blood and improving the oxygen-carrying capacity. We present a case of sickle cell crisis (SCC) managed with automated RCE and also reviewed the literature to assess the utilization and clinical efficiency of this therapy in India. A 19-year-old gentleman diagnosed with SCA presented with acute chest syndrome. Hemoglobin (Hb) was 8.8 g%, hematocrit (HCT) was 24%, and HbS was 90%. As there was worsening of symptoms with conventional management, the patient underwent two procedures of automated RCE. The clinical condition of the patient was improved, HbS was reduced to 16% and HCT was remained at 21% postprocedure. Articles on automated RCE in SCA conducted in India were reviewed and four articles were analyzed based on the search strategy. All the included articles concluded automated RCE as an effective procedure for complications of SCA. Common indication in India was SCA patients undergoing surgery as a prophylactic measure. Automated RCEs are promising as an acute treatment for indicated sickle cell complications. This therapy is underutilized in the Indian scenario, especially in patients with SCC.

OBJECTIVE: To report a rare case of spontaneous bilateral epidural hematoma (EDH) in a 10-year-old Nigerian child with sickle cell disease (SCD) and review the literature regarding this unusual complication.
METHODS: We present a case of a pediatric patient with SCD who developed a spontaneous bilateral EDH and discuss the potential underlying mechanisms, management approaches, and outcomes. We also conducted a literature review of existing cases of spontaneous EDH in patients with SCD.
RESULTS: Our patient initially presented with a subgaleal hematoma and underlying bilateral EDH, but she was sent home without any neurosurgical consultation. Two years later, she returned with altered consciousness and left-sided weakness, revealing an increased size of the EDH with a noticeable mass effect. She underwent a successful emergency bilateral craniotomy, with noticeable improvement in her level of consciousness and left-sided weakness post-operatively. In our literature review, we found 40 reported cases of spontaneous EDH in SCD patients, with a male predominance (82.5%). The average age of patients was 15.282 years. The most common hematoma location was bifrontal (20%) and the most reported symptom was headache (47.5%). Most patients (97.5%) were already known cases of SCD. Among those treated, 77.5% survived.
CONCLUSIONS: Spontaneous bilateral EDH in SCD patients is an uncommon complication, with a variety of proposed pathophysiological mechanisms. Prompt recognition and appropriate management, either conservative or surgical, are crucial to improve outcomes. Our case and literature review underscore the importance of considering spontaneous EDH in SCD patients presenting with neurological symptoms, even in the absence of trauma. Further research is needed to elucidate the precise etiology, identify risk factors, and optimize management approaches for this rare complication in SCD patients.

UNASSIGNED: Major sickle cell syndromes are subjected to a high frequency of hemolysis, infections, oxidative stress, and vasooclusive crises which promote inflammation and iron balance disorders. We aimed to systematically review and analyze the studies in this patients addressing in general, and Africa in particular.
UNASSIGNED: The systematic review of published articles in the Pubmed and Google Scholar databases was carried out according to the recommendations of the PRISMA model. The case-control articles have been included. The data extracted from the articles were analyzed using statistical software R. The standardized mean difference (SMD) was used to assess the extent of the disease on the different variables studied.
UNASSIGNED: At the end, 128 articles were obtained; but only 33 were elligible for meta-analysis. A SMD of -1.79 was obtained for hemoglobin between the sickle cell patients and the controls due to the deviation from the overall mean hemoglobin in the cases (8 ± 2 g/dL) and in controls (13 ± 3 g/dL). Sickle cell disease showed a significant extent on ferritin [SMD = 2.61; (95% confidence interval, CI: 2.39-2.83); (p < 0.01)] compared to non-sickle cell patients thus describing a higher risk for sickle cell sufferer to have ferritin disorders. The included studies also described the influence of sickle cell anemia on serum iron [SMD = 1.52; (95% CI: 1.32-1.76); (p < 0.01)] compared to normal subjects. The high risk of inflammation has been described as higher in sickle cell patients [SMD = 0.38; (95% CI: 0.25-0.50)], reflecting the moderate extent of sickle cell disease on inflammation.
UNASSIGNED: Patients with major sickle cell syndrome in inflammation have a higher risk of iron profile disorders compared to the normal population. Further studies are needed to explore mechanisms for preventing the deleterious effects of iron from this hemolysis, for example haptoglobin genotyping.

In pregnancies complicated by sickle cell disease (SCD), the maternal-fetal dyad is at high risk for mortality and morbidity. In healthy pregnancies, maternal nutritional status is a critical factor for the healthy growth and development of the fetus. However, there are no reviews of the current research on the nutritional status of pregnant women with SCD and pregnancy outcomes. First, we aim to assess the burden of malnutrition in pregnant women with SCD. Next, we aim to systematically evaluate if pregnant women with SCD who have poor nutritional status are at increased risk for adverse birth outcomes compared to pregnant women with sickle cell disease and normal nutritional status. We will systematically search multiple electronic databases. Our exposure is pregnant women with SCD and poor nutritional status. The primary outcomes of interest include low birth weight (categorical) and birth weight z-scores (continuous). We will also evaluate maternal and perinatal outcomes as secondary outcomes. We will evaluate the risk of bias and overall certainty of evidence with Risk of Bias in Non-randomized Studies-of Interventions (ROBINS-I), and the overall evidence will be assessed using Grading of Recommendation Assessment, Development, and Evaluation (GRADE) criteria. We will pool findings with a meta-analysis if sufficient homogeneity exists among studies. Findings will be published in a peer-reviewed journal and disseminated to SCD advocacy groups. PROSPERO registration number: 429412.

Sickle cell disease (SCD) is an inherited monogenic disorder with high prevalence throughout sub-Saharan Africa, the Mediterranean basin, the Middle East, and India. Sources of SCD epidemiology remain scarce and fragmented. A systematic literature review (SLR) to identify peer-reviewed studies on SCD epidemiology was performed, with a search of bibliographic databases and key conference proceedings from 1 January 2010 to 25 March 2022 (congress abstracts after 2018). The SLR followed PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. Meta-analyses, using a binomial normal random-effects model, were performed to estimate global and regional prevalence and birth prevalence. Of 1770 journal articles and 468 abstracts screened, 115 publications met the inclusion criteria. Prevalence was highest in Africa (~800/100,000), followed by the Middle East (~200/100,000) and India (~100/100,000), in contrast to ~30/100,000 in Europe. Birth prevalence was highest in Africa (~1000/100,000) and lowest in North America (~50/100,000) and Europe (~30/100,000). This SLR confirmed that sub-Saharan and North-East Africa, India, the Middle East, and the Caribbean islands are global SCD hotspots. Publications including mortality data were sparse, and no conclusions could be drawn about mortality. The identified data were limited due to gaps in the published literature for large parts of the world population; the inconsistent reporting of SCD genotypes, diagnostic criteria, and settings; and a sparsity of peer-reviewed publications from countries with assumed high prevalence. This SLR demonstrated a lack of systematic knowledge and a need to provide uniform data collection on SCD prevalence and mortality.

Sickle cell disease is an autosomal recessive disorder of the beta-globin gene, with resultant deformation of the red blood cells and variable clinical outcomes. Nigeria is recognised as the country with the highest burden of sickle cell disease globally. This study aimed at critically reviewing available literature on impact of sickle cell disease in Nigeria. A literature search was carried out on four databases, and a total of 116 articles that met the inclusion criteria were included in the critical review. It was observed that majority of the studies were carried out in South-Western part of Nigeria (47.4%), whilst the North-East had the least number of studies undertaken in this area, more than a quarter of the studies (27.6%) were related to hematologic and serologic screening. Major themes that emerged from this review were morbidity and mortality; prevalence of sickle cell disease; issues relating to blood transfusion; psychosocial impact; and anatomical dysfunction in sickle cell disease. Intervention programs from both government and non-governmental organizations aimed at reducing the burden of sickle cell disease and its socio-economic impact were identified as key to strategies aimed at overcoming challenges associated with the disease. Findings from this study also revealed that education and awareness interventions were central to reducing the prevalence of sickle cell disease in this setting.

Inconsistent therapeutic responses have been observed among patients with sickle cell anemia (SCA) undergoing hydroxyurea (HU) following the adoption of the standardized protocol. Moreover, this treatment regimen necessitates a prolonged period to reach the maximum tolerated dose in which beneficial therapeutic effects are observed in most SCA patients. To overcome this limitation, several studies have performed HU dose adjustments in SCA patients based on individualized pharmacokinetic profiles. The present systematic mini-review aims to select and analyze published data to present an overview of HU pharmacokinetics studies performed in SCA patients, as well as evaluate the effectiveness of the dose adjustment strategy. A systematic search was performed in the Embase, Pubmed, Scopus, Web of Science, Scielo, Google Scholar, and the Virtual Library of Health databases from December 2020 to August 2022, with a total of five studies included. Inclusion criteria consisted of studies in which the dose adjustment was performed in SCA patients based on pharmacokinetic parameters. Quality analyzes were performed using QAT, while data synthesis was performed according to the Cochrane Manual of Systematic Reviews of Interventions. Analysis of the selected studies revealed improved HU treatment effectiveness using personalized dosages in SCA patients. Moreover, several laboratory parameters were utilized as biomarkers of the HU response, and methods designed to simplify the adoption of this practice were presented. Despite the scarcity of studies on this topic, HU-personalized treatment based on individualized pharmacokinetic profiles represents a viable alternative for SCA patients who are candidates for HU therapy, especially for pediatric patients. Registration number: PROSPERO CRD42022344512.