Complications Of Sickle Cell Disease Research Articles

Lipid and hemolysis parameters predicting acute chest syndrome in adulthood with sickle cell disease

Sickle cell disease (SCD) is a lifelong blood disorder affecting approximately 100,000 people in the United States and is one of the most common monogenic diseases. A serious complication of SCD is acute chest syndrome (ACS). ACS is a condition with a high rate of morbidity and mortality. The aim of the study was to assess hemolysis and lipid parameters in a cohort of confirmed SCD patients to predict ACS development in the following year.Standard lipid were performed (triglycerides, total cholesterol, high-density cholesterol, low-density cholesterol) panel to calculate of non-HDL-C, large buoyant LDL cholesterol (lbLDL-C) and small dense LDL cholesterol (sdLDL-C) with Sampson equation. Hemolysis and hematologic parameters were also evaluated.Among 91 patients included between September 2018 and June 2021, thirty-seven patients had history of ACS and 6 patients developed ACS during following year. In unadjusted logistic regression, total bilirubin was associated with ACS occurrence (RR: 1.2 [1.05–1.51] p = 0.013). Concerning lipid profile, non-HDL-C (RR: 0.87 [0.0.67–0.99] p = 0.04) and sdLDL-C (RR: 0.78 [0.49–0.96] p = 0.03) were associated with ACS occurrence decrease. C-reactive protein was associated with ACS occurrence (RR: 1.27 [1.065–1.85] p = 0.011).Based on these findings, this study demonstrated that several biomarker easily available can be used at steady state to predict ACS in the following year. The validation of these results are required to ensure the reproducibility of the findings.

The many faces of sickle cell disease in children: complications in the appendicular skeleton.

Sickle cell disease (SCD) is a hereditary red cell disorder with clinical manifestations secondary to sickling or crescent-shaped distortion of the red blood cells. Musculoskeletal complications of SCD are often the main causes for acute and chronic morbidities in children with manifestations including osteomyelitis, osteoporosis and osteonecrosis. This article aims to familiarise the paediatric radiologist with appendicular skeletal complications of SCD in the paediatric population and their imaging appearance.

Sickle Cell Disease Complications and BMI Percentiles of Pediatric Patients

BMI percentile is a good index of nutritional status among pediatric patients. Yet there is a dearth of information about the relationship between this important anthropometric parameter and specific severity indices among pediatric patients. The study is designed to explore the possibility of such a relationship. Methods: Pediatric study participants were divided into test [HbSS, HbSC] and control [HbAA] groups. The questionnaire was administered to obtain information on age, gender, and clinical features of the disease [pain frequency, leg ulcer, priapism]. The anthropometry indices were determined. BMI as well as BMI percentiles were calculated. Data were summarized using relative frequency, mean, and standard deviation while analysis of variance, LSD post hoc tests and Chi‑squared tests were used for inferential statistics. Significant levels were set with P < 0.05. Results: There were significant differences in the body weight, height and BMI of HbAA, HbSC and HbSS. The distribution of the BMI percentiles for the three genotypes showed that 5% of HbAA, 20% of HbSC, and 35.7% of HbSS were in unhealthy categories. The occurrence of leg ulcers and priapism among the two SCD genotypes was 0% and 3.57% respectively. The Chi-square tests showed a significant difference between BMI percentiles (X2=72.51; P=<.001) or painful episodes (X2=15.992; P=.003) and hemoglobin genotypes [HbSS, HbSC]. Among SCD patients there was a relationship between BMI percentiles and pain frequency (X2=50.59; P=<.001). Conclusion: The study suggests that SCD impacts BMI percentiles. Also, the frequency of occurrence of priapism and leg ulcers varied widely, indicating that priapism among the SCD patients may be a more common SCD complication than leg ulcer in the region. The fact that there was a higher frequency of pain among HbSS than HbSC suggests a bias in distribution of pain frequency in the 2 hemoglobinopathies.

Clinical Practice Patterns in Sickle Cell Disease Treatment: Disease-Modifying and Potentially Curative Therapies.

Therapeutic options for sickle cell disease (SCD) have increased recently as well as the development of updated national guidelines. It is not known how these options are being offered or to what degree guidelines are incorporated into clinical practice. This study aimed to describe practice patterns for pediatric hematologists regarding the use of disease-modifying and potentially curative therapies for SCD. A 9-section, cross-sectional electronic survey was disseminated during a 3-month period via SurveyMonkey, to members of the American Society of Pediatric Hematology/Oncology Hemoglobinopathy Special Interest Group (ASPHO HSIG). A total of 88 physician members of the ASPHO HSIG were surveyed. Ninety percent of respondents (72/80) start hydroxyurea routinely in patients with HbSS and HbSβ0 thalassemia, regardless of disease severity. Laboratory monitoring was recommended every 3 months for stable dosing in 63.8% (51/80). New therapies were recommended for patients on hydroxyurea who were still experiencing SCD complications: L-glutamine 68.5% (37/54) or crizanlizumab 93.1% (54/58). Voxelotor was recommended for patients on hydroxyurea with low hemoglobin in 65.1% (43/66) of cases. Matched sibling transplant was considered for any disease severity by 55.1% (38/69). Gene therapy trials are offered on-site by 29% (20/69). Our study demonstrated the enhanced utilization of hydroxyurea while revealing the unexplored potential of other disease-modifying therapies in SCD. These findings underscore the importance of continued knowledge acquisition about the long-term efficacy of new medical therapies and addressing barriers to the use of proven therapies and guide the development of future studies of optimal SCD management.

Evaluation of renal function of sickle cell children in Libreville by estimation of glomerular creatinine-cystatin C filtration rate: prevalence of acute kidney injury and associated factors

Background: Sickle cell disease (SCD) is an important and growing global health problem. Kidney damage is one of the most common complications of SCD. We aimed to determine the prevalence of acute kidney injury (AKI) in children with SCD in our context. Methods: Cross-sectional and analytical study from January 2022 to September 2022, including SCD children aged from 6 months to 17 years during their hospitalisation. We measured the estimated glomerular filtration (eGFR) rate using the combined creatinine and cystatin C formula for kids (CKiDScr-Cys C). Univariate analyses were performed to measure the relationship between variables and AKI and eGFR, followed by a multivariate analysis using logistic regression. Results: Of the 137 children, we included 82 boys (60%) and 55 girls (40%). The mean eGFR was 112±45.3 ml/min/1.73 m2. A total of 36 subjects, or 26.3% (95% CI [18.9-33.6%)), had acute AKI. Comparison of characteristics by AKI status showed significant differences according the number of transfusions (p<0.01), and hemoglobin level (p<0.027), eGFR had a negative correlation with the number of transfusions r=-0.308 (-0.477; -0.117); p<0.01. Multivariate analysis showed that nutritional status was a protective factor of AKI (p<0.01), and the number of transfusions was a predictive factor of AKI in SCD in our context (p<0.001). Conclusions: The results from our study are an urgent alarm to implement the existing management programs on SCD from screening to universal access of hydroxyurea in order to reduce complications and mortality related to this pathology.

New Horizons in Emergency Department Management of Pediatric Sickle Cell Disease.

Sickle cell disease (SCD) is an important topic for emergency medicine audiences because complications of the disease account for a large proportion of hematologic emergencies that are seen in the emergency department each year. Early recognition and aggressive management of emergency complications of SCD can help to reduce the morbidity and mortality associated with this disease. Although the treatment recommendations for some complications of SCD are based on expert opinion, there has been advancement in the understanding of the pathogenesis of the disease and evidence regarding the treatment options available for managing acute complications. This continuing medical education article will provide a summary of the clinical manifestation and management of the most common acute complications of SCD: infection, vaso-occlusive episode, acute chest syndrome, splenic sequestration, stroke, and priapism.

Clinical management of complications of sickle cell disease in the emergency room: literature review

Clinical management of complications of sickle cell disease in the emergency room: literature review

Assessment of visual and blood-related parameters among children with sickle cell anaemia at Murtala Muhammad Specialist Hospital in Kano, Nigeria.

Sickle cell disease (SCD) is a prevalent genetic disease worldwide and particularly in Nigeria. Retinopathy is a known complication of SCD, underscoring the need to assess visual parameters in children. This study aimed to evaluate the visual acuity (VA), color vision (CV), packed cell volume (PCV), and erythrocyte sedimentation rate (ESR) of Sickle cell anemic (SCA) patients attending the Sickle cell counseling unit of Murtala Muhammad Specialist Hospital (MMSH) in Kano. It was a descriptive cross-sectional study consisting of 60 participants, including 30 SCA patients and 30 healthy controls without systemic or ocular diseases, aged between 8 and 14 years. Visual acuity, CV, PCV, and ESR were assessed using Snellen Chart, Ishihara chart, Hematocrit test, and Westergren Method respectively. Data were analyzed using SPSS version 22.0. Statistical significance was set at P < 0.05. Both SCA patients and controls demonstrated limited knowledge about VA, CV, and ESR tests, and a significant percentage had never undergone these tests. SCA patients exhibited mild to moderate visual impairment (VI) in both eyes, while controls had no VI. Abnormally low PCV and ESR values were observed in all SCA patients, whereas controls had normal values. Gender differences were observed in ESR levels, with females showing higher levels. Significant differences were found between controls and SCA patients in terms of VA, ESR, and PCV values. There was a general lack of awareness regarding the importance of VA and CV tests in the community. Visual impairment and abnormal PCV and ESR values were exclusive to the SCA patients, indicating their association with the disease.

Pulmonary Hypertension in Sickle Cell Disease: Novel Findings of Gene Polymorphisms Related to Pathophysiology.

Pulmonary hypertension (PH) is a progressive and potentially fatal complication of sickle cell disease (SCD), affecting 6-10% of adult SCD patients. Various mechanisms and theories have been evaluated to explain the pathophysiology of this disease. However, questions remain, particularly regarding the clinical heterogeneity of the disease in terms of symptoms, complications, and survival. Beyond the classical mechanisms that have been thoroughly investigated and include hemolysis, nitric oxide availability, endothelial disorders, thrombosis, and left heart failure, attention is currently focused on the potential role of genes involved in such processes. Potential candidate genes are investigated through next-generation sequencing, with the transforming growth factor-beta (TGF-β) pathway being the initial target. This field of research may also provide novel targets for pharmacologic agents in the future, as is already the case with idiopathic PH. The collection and processing of data and samples from multiple centers can yield reliable results that will allow a better understanding of SCD-related PH as a part of the disease's clinical spectrum. This review attempts to capture the most recent findings of studies on gene polymorphisms that have been associated with PH in SCD patients.

Acute care utilization among individuals with sickle cell disease and related cardiopulmonary and renal complications.

Cardiopulmonary and renal end organ (CPR) complications are associated with early mortality among individuals with sickle cell disease (SCD). However, there is limited knowledge regarding acute care utilization for individuals with SCD and CPR complications. Our objective was to determine the prevalence of CPR complications in a state specific SCD population and compare acute care utilization among individuals with and without CPR complications. We leveraged 2017-2020 data for individuals with SCD identified by the Sickle Cell Data Collection program in Wisconsin. The prevalence of CPR complications is determined for distinct age groups. Generalized linear models adjusted for age compared the rate of acute care visits/person/year among individuals who had cardiopulmonary only, renal only, both cardiopulmonary and renal, or no CPR complications. There were 1378 individuals with SCD, 52% females, mean (SD) age 28.3 (18.5) years; 48% had at least one CPR complication during the study period. The prevalence of CPR complications was higher in adults (69%) compared to pediatric (15%) and transition (51%) groups. Individuals with SCD and cardiopulmonary complications had higher acute visit rates than those without CPR complications (5.4 (IQR 5.0-5.8) vs 2.4 (IQR 2.1-2.5), p <0.001)). Acute care visit rates were similar between individuals with SCD who had renal only complications and no CPR complications (2.7 (IQR 2.5-3.0) vs 2.4 (2.1-2.5), p = 0.24). The high acute care visit rates, especially for those with cardiopulmonary complications, warrant further investigation to understand risk factors for CPR complications, the underlying reasons and identify effective disease management strategies.

Prevalence of hearing loss in patients with sickle cell disease in the southeast of Iran

Background: One of the complications of sickle cell disease (SCD) is hearing loss. The purpose of the present study is to determine the prevalence of hearing loss in SCD.&#x0D; Materials and Methods: This is a descriptive-analytical cross-sectional study conducted on 100 patients with SCD in 2019-2020. All the patients underwent otololaryngological examination and audiometric tests to assess their hearing status. The type and severity of hearing loss were determined, the demographic information of the patients was recorded, and the data were analyzed using the SPSS software version 21, a Chi-square test, and the Kruskal-Wallis test. The P-values of &lt; 0.05 were considered statistically significant.&#x0D; Results: The mean age of the patients was 17.6 ± 10.8 years. Of them, 60% were male. Hearing loss was diagnosed in 26 patients (26%), 16 of whom had sensorineural hearing loss (SNHL) and 10 had conductive hearing loss (CHL). In terms of the disease severity, 12, 10, 3 and 1 patients had mild, moderate, severe and profound hearing loss, respectively. The mean age of the patients with SNHL was significantly higher than the median age of the subjects with CHL (p-value = 0.043). Also, the patients with hearing loss had no statistically significant difference in terms of the variables of age, gender, unilateral or bilateral ear involvement and type of SCD (p-value = 0.069).&#x0D; Conclusion: This study revealed a hearing loss frequency of 26% among patients with SCD. Regular hearing assessment and timely treatment and rehabilitation measures are recommended for these patients.

Serum iron Profile of Patients with Sickle Cell Disease and its Association with Socio-demographic Characteristics and Duration of Diagnosis.

Sickle cell anemia is the most common hemoglobinopathy in the world. The study aimed to evaluate the iron profile and its association with socio-demographic characteristics in patients with sickle cell disease. A hospital-based descriptive cross-sectional study was conducted to know the iron profile and its socio-demographic association in patients with sickle cell disease. The average serum iron, TIBC, and transferrin saturation were 16.75 ± 6.40 mcgMole/L, 69.46 ± 16.94 mcg/dl and 25.15 ± 12.51% respectively. The serum ferritin ranged from 10.00 to 3000.00 ng/ml. The proportion of participants with normal serum iron, TIBC, serum ferritin, and transferrin saturation were 86.10%, 0.00%, 33.90% and 36.40% respectively. All of the participants of this study had low TIBC (1005), and more than half of the participants had elevated serum ferritin (56.40%). Iron overload is a common complication of sickle cell disease. There was no association of age and sex with iron profile. The TIBC variation between the Chaudhary ethnic group compared to other ethnic groups signifies the ethnic role in the iron profile.

Early-onset indicators of a hypercoagulable state and clinical complications in a cohort of children with sickle cell trait.

Adults with sickle cell trait (SCT) have a procoagulant state with increased risk of thromboembolism, but limited data are available for children. We compared the coagulation profile of children with SCT, different sickle cell disease (SCD) genotypes, and healthy controls. Compared to controls and similarly to HbSC patients, 41 SCT children (mean age 6.85years; 20 males; 88% Africans) had a characteristic procoagulant profile: higher levels of factor VIII, von Willebrand factor (VWF) Ag and CBA, D-dimer; lower levels of ADAMTS 13 activity, ADAMTS13 activity: VWFAg, plasminogen activator inhibitor, tissue plasminogen activator. Moreover, 13/41 had clinical complications of SCD, five requiring hospitalization.

Is There any Relationship Between the Repeated Complications of Sickle Cell Disease and the Potential Development of Acute Leukemia?

Sickle cell disease (SCD) is a severe monogenic hereditary hemoglobinopathy that is characterized by repeated clinical and biological manifestations able to generate stress erythopoiesis. A clonal hematopoiesis involving mainly variants of TP53, DNMT3A, ASXL1, and/or TET2 may be more prevalent in patients with SCD, suggesting that mutations in these genes may lead to an increased risk of leukemia. An increased prevalence of leukemia in patients with SCD has been confirmed by an increasing number of acute myeloid leukemia cases with myelodysplastic features reported in this patient population even in the absence of disease-modifying treatments. This leads to the hypothesis of a mechanism involving multifactorial causes through the pathophysiologic manifestations of SCD, in which cells are undergoing constant hematopoietic hyperplasia, inducing genomic damage and somatic mutations.

Comparative transcriptomic analysis of circulating endothelial cells in sickle cell stroke.

Ischemic stroke (IS) is one of the most impairing complications of sickle cell anemia (SCA), responsible for 20% of mortality in patients. Rheological alterations, adhesive properties of sickle reticulocytes, leukocyte adhesion, inflammation and endothelial dysfunction are related to the vasculopathy observed prior to ischemic events. The role of the vascular endothelium in this complex cascade of mechanisms is emphasized, as well as in the process of ischemia-induced repair and neovascularization. The aim of the present study was to perform a comparative transcriptomic analysis of endothelial colony-forming cells (ECFCs) from SCA patients with and without IS. Next, to gain further insights of the biological relevance of differentially expressed genes (DEGs), functional enrichment analysis, protein-protein interaction network (PPI) construction and in silico prediction of regulatory factors were performed. Among the 2469 DEGs, genes related to cell proliferation (AKT1, E2F1, CDCA5, EGFL7), migration (AKT1, HRAS), angiogenesis (AKT1, EGFL7) and defense response pathways (HRAS, IRF3, TGFB1), important endothelial cell molecular mechanisms in post ischemia repair were identified. Despite the severity of IS in SCA, widely accepted molecular targets are still lacking, especially related to stroke outcome. The comparative analysis of the gene expression profile of ECFCs from IS patients versus controls seems to indicate that there is a persistent angiogenic process even after a long time this complication has occurred. Thus, this is an original study which may lead to new insights into the molecular basis of SCA stroke and contribute to a better understanding of the role of endothelial cells in stroke recovery.

Spontaneous Extradural Hematoma in a Sickle Cell Anemia Patient with Hyperinflammation and Thrombotic Microangiopathy successfully treated with Eculizumab: A case report and review of the literature.

Background The event of extradural hematoma in the absence of head trauma is a rare central nervous system complication of sickle cell disease. We report here a case of spontaneous extradural hematoma in a patient being treated for sickle cell vaso-occlusive crisis complicated by hyperinflammation and thrombotic microangiopathy. The significance of inflammation as an integral component of the pathomechanism of vaso-occlusive crisis in patients with sickle cell disease and the role of heme in activating the complement system's alternative pathway are highlighted in this case report. Case Presentation A teenage patient with sickle cell disease developed a spontaneous right parietal extradural hematoma while receiving treatment for sickle cell vaso-occlusive crisis. The concurrent events of hyperinflammation, disseminated intravascular coagulation, hyperhemolysis syndrome, thrombotic microangiopathy and refractory post-operative bleeding complicated this patient's clinical course after surgical evacuation of extradural hematoma. This patient was subsequently treated with eculizumab and improved in the days following. Conclusion Treatment with the anti-C5 monoclonal antibody eculizumab which targets and inhibits terminal complement system activation reversed the deleterious cascade of events in this patient with sickle cell disease.

Nontargeted Plasma Proteomic Analysis of Renal Disease and Pulmonary Hypertension in Patients with Sickle Cell Disease.

Sickle cell disease (SCD) is characterized by red blood cell sickling, vaso-occlusion, hemolytic anemia, damage to multiple organ systems, and, as a result, shortened life expectancy. Sickle cell disease nephropathy (SCDN) and pulmonary hypertension (pHTN) are common and frequently co-occurring complications of SCD; both are associated with markedly accelerated mortality. To identify candidate circulating biomarkers of SCDN and pHTN, we used mass spectrometry to quantify the relative abundance of >1000 proteins in plasma samples from 189 adults with SCD from the Outcome Modifying Genes in SCD (OMG-SCD) cohort (ProteomeXchange identifier PXD048716). Forty-four proteins were differentially abundant in SCDN, most significantly cystatin-C and collagen α-1(XVIII) chain (COIA1), and 55 proteins were dysregulated in patients with SCDN and pHTN, most significantly insulin-like growth factor-binding protein 6 (IBP6). Network analysis identified a module of 133 coregulated proteins significantly associated with SCDN, that was enriched for extracellular matrix proteins, insulin-like growth factor binding proteins, cell adhesion proteins, EGF-like calcium binding proteins, and several cadherin family members. Collectively, these data provide a comprehensive understanding of plasma protein changes in SCDN and pHTN which validate numerous studies of chronic kidney disease and suggest shared profiles of protein disruption in kidney dysfunction and pHTN among SCD patients.

Soluble guanylate cyclase stimulators and activators: new horizons in the treatment of priapism associated with sickle cell disease.

Priapism, defined as a prolonged and often painful penile erection occurring without sexual stimulation or desire, is a common complication in sickle cell disease (SCD), affecting up to 48% of male patients. This condition presents significant clinical challenges and can lead to erectile dysfunction if not properly managed. Current pharmacological treatments for SCD-related priapism are primarily reactive rather than preventative, highlighting a gap in effective medical intervention strategies. A critical factor in developing priapism is the reduced basal bioavailability of nitric oxide (NO) and cyclic guanosine monophosphate (cGMP) in erectile tissues. New prevention strategies should ideally target the underlying pathophysiology of the disease. Compounds that stimulate and activate soluble guanylate cyclase (sGC) emerge as potential therapeutic candidates since these compounds have the property of inducing cGMP production by sGC. This review explores the potential of sGC stimulators and activators in treating priapism associated with SCD. We discuss the advantages of these agents in the face of the challenging pathophysiology of SCD. Additionally, the review underscores the impact of intravascular hemolysis and oxidative stress on priapism pathophysiology in SCD, areas in which sGC stimulators and activators may also have beneficial therapeutic effects.

Hydroxyurea for secondary stroke prevention in children with sickle cell anaemia: a systematic review of clinical evidence and outcomes

Background: Stroke remains one of the leading complications of sickle cell anaemia (SCA) in children. Traditionally, SCA treatment focused on symptom relief. However, the high incidence of strokes in children has prompted a reevaluation of treatment, particularly hydroxyurea, for secondary stroke prevention. This study assesses hydroxyurea’s effectiveness and safety in preventing secondary strokes in paediatric SCA patients. Methods: This systematic review followed a pre-defined protocol registered with PROSPERO. Comprehensive searches were conducted across PubMed, Embase, Scopus, MEDLINE, Google Scholar, and the Cochrane Library up to August 2023. Studies were included involving paediatric SCA patients at risk of secondary stroke, assessing hydroxyurea as the primary intervention. Results: A total of six studies meeting inclusion criteria were included. The effectiveness of hydroxyurea in preventing secondary strokes, with variable responses reported across studies. Adverse effects, including mild neutropenia, are associated with hydroxyurea treatment but with variability in reported toxicity levels. Conclusion: Hydroxyurea holds promise in preventing recurrent strokes in children with SCA, though its efficacy and safety profiles vary among individuals. Optimal dosages and treatment durations require further investigation, necessitating vigilant monitoring of haematological parameters. Future research should refine dosing strategies, consider individual patient characteristics, assess long-term effects, and explore ancillary benefits beyond stroke prevention.

Hydroxyurea is associated with later onset of acute splenic sequestration crisis in sickle cell disease: Lessons from the European Sickle Cell Disease Cohort-Hydroxyurea (ESCORT-HU) study.

Acute splenic sequestration crisis (ASSC) is a potentially life-threatening complication of sickle cell disease (SCD), typically occurring in young patients under 5 years of age, with a median age at first episode of less than 2 years. Because a beneficial effect of hydroxyurea (HU) on spleen perfusion and splenic function has been suspected, we hypothesized that HU treatment might be associated with later onset of ASSC in patients with SCD. To investigate this hypothesis, we analyzed data from the ESCORT-HU study on a large cohort of patients with SCD receiving HU, enrolled between January 2009 and June 2017 with a follow-up of 7309 patient-years of observation. The median age at ASSC of the 14 patients who experienced a first episode of ASSC during the study period was 8.0 [IQR: 5.0-24.1] years. The median age at HU initiation was significantly lower in these 14 patients (4.8 [IQR: 3.3-18.7] years) compared to the 1664 patients without ASSC (19.9 [8.8-33.4] years, p = .0008). These findings suggest that ASSC may occur at an unusually late age in patients receiving HU, possibly reflecting longer preservation of spleen perfusion and function secondary to early initiation of HU. Further studies are needed to better characterize the effects of HU on spleen perfusion/function and on the occurrence of ASSC in patients with SCD (ClinicalTrials.gov identifier: NCT02516579; European registry ENCEPP/SDPP/10565).