Search Results (141)

Background/Objectives: Osteoarticular infections are common complications of sickle cell disease (SCD), often posing significant challenges in diagnosis and management. They primarily affect children: however, the recurrence or emergence of these infections in adults as new complications is well documented. Despite this, there is a notable lack of literature focused on diagnosis and management strategies for adult SCD patients. Our research aims to explore the management challenges in adult SCD patients and to evaluate the outcomes of a selected conservative management approach. Methods: The authors conducted a single-center retrospective observational study from January 2018 to December 2022. All adult SCD patients admitted with suspected or confirmed osteoarticular infections were included. Relevant data were meticulously extracted from patients’ hard and electronic medical files. Descriptive statistics were used to present the frequencies and percentages, and suitable statistical analyses were employed to identify specific clinical features and management outcomes in adult patients with SCD. Results: Thirty-one patients with osteoarticular infections were included; the majority were males (87.1%) with a mean age of 26.55 years. Long bones were frequently affected, with femurs being the most infected sites (28.1%). Infection recurred in 41.9% of patients. Most patients were managed conservatively (93.5%), primarily with clindamycin and ciprofloxacin, for approximately six weeks, resulting in an excellent cure rate of 96.8%. Conclusions: The current study highlights the specific clinical features of osteoarticular infections in adult patients with SCD, identifies radiological findings on Magnetic Resonance Imaging, and suggests a conservative, non-invasive approach for management with excellent outcomes. Full article

Acute chest syndrome (ACS) is a life-threatening complication of sickle cell disease (SCD) with complex infectious and non-infectious etiologies. Bacterial pathogens, including Streptococcus pneumoniae, Haemophilus influenzae, and atypical organisms such as Mycoplasma pneumoniae, play crucial roles in ACS pathogenesis, particularly in immunocompromised SCD patients with functional asplenia. Despite the importance of infectious triggers, regional data on pathogen identification rates and antimicrobial management strategies in ACS remain limited, especially from high-prevalence SCD regions. This study aimed to investigate the infectious etiologies, pathogen identification patterns, and antimicrobial management outcomes of ACS in adult SCD patients in Eastern Saudi Arabia. A five-year retrospective analysis was conducted on patients aged ≥14 years with SCD who were admitted with ACS to Dammam Medical Complex between 2018 and 2022. Comprehensive microbiological evaluation included blood cultures, sputum cultures, and atypical pathogen testing (Mycoplasma pneumoniae, Chlamydia pneumoniae). Data on antimicrobial regimens, pathogen identification rates, vaccination status against encapsulated bacteria, and clinical outcomes were systematically analyzed. Empirical antibiotic strategies and their effectiveness in this immunocompromised population were evaluated. A total of 60 adult SCD patients experiencing 80 episodes of ACS were included. Despite comprehensive microbiological workup, specific infectious pathogens were identified in only 8 (10.0%) episodes, highlighting the complex multifactorial etiology of ACS. Blood cultures yielded pathogens in 5 (6.3%) cases, sputum cultures in 4 (5.0%) cases, and Mycoplasma pneumoniae was identified in 3 (3.8%) episodes. All patients received empirical broad-spectrum antimicrobial therapy, with ceftriaxone and azithromycin combination being the most frequent regimen (76 cases, 95.0%), providing coverage for both typical and atypical bacterial pathogens. Antibiotic escalation was required in 16 (20.0%) episodes. Vaccination rates against Streptococcus pneumoniae were suboptimal at 30 (50.0%), representing a significant risk factor for invasive bacterial infections in this functionally asplenic population. The intensive care unit (ICU) admission rate was 15 (18.8%), and in-hospital mortality was 3 (3.8%), with infectious complications contributing to severe outcomes. In this cohort of SCD patients, ACS demonstrated low rates of specific pathogen identification despite systematic microbiological investigation, supporting the multifactorial infectious and non-infectious etiology of this syndrome. The predominant use of broad-spectrum antimicrobial therapy targeting both typical and atypical bacterial pathogens proved effective in this immunocompromised population. However, suboptimal vaccination rates against encapsulated bacteria represent a critical gap in infection prevention strategies. These findings emphasize the importance of empirical antimicrobial coverage for suspected bacterial pathogens in ACS management and highlight the urgent need for enhanced vaccination programs to prevent infectious complications in functionally asplenic SCD patients. Full article

Background: Sickle cell disease (SCD) affects more than 100,000 people in the United States and 8 million people worldwide, with high morbidity and mortality and musculoskeletal (MSK) complications that contribute to functional disability. However, MRI-based characterization of musculoskeletal manifestations remains limited in high-prevalence regions, including the Middle East. This study aimed to review MRI findings of MSK manifestations in SCD patients and assess associations with clinical characteristics. Methods: A retrospective study was conducted on 96 patients with SCD who underwent MSK MRI between 2012 and 2022 at King Abdulaziz University Hospital. Patient demographics, clinical characteristics, and imaging findings were reviewed. The prevalence and distribution of MSK complications were analyzed across age, gender, and BMI categories. Results: Of the 96 patients (47% males; 53% females; mean age 28.9 years), the hip was the most frequently scanned region (46%), followed by the leg, femur, shoulder, and knee. Bone infarction was the most common complication, observed in 57 patients (59.3%), and was more prevalent among older adults. Osteomyelitis was identified in 16 patients (16.7%), with higher rates in children and underweight individuals. Decreased bone marrow signal intensity was seen in 11 patients (11.4%), particularly in older age groups. Other findings and unremarkable scans each accounted for 6 cases (6.3%). Gender analysis showed broadly similar patterns, although decreased marrow signal intensity was more common in females. Conclusions: MRI is an effective imaging modality for detecting and differentiating MSK complications in SCD. Routine use of MRI in follow-up care is recommended to facilitate early diagnosis, guide management, and prevent long-term disability. Larger prospective studies are needed to validate these findings and establish MRI as a routine diagnostic tool for SCD. Full article

Introduction: Sickle cell anemia (SCA) is a hereditary hemoglobinopathy caused by a mutation in the beta-globin gene, resulting in the production of hemoglobin S. Intracranial hemorrhage (ICH) is a severe complication for patients with SCA, but there is a paucity of literature on its epidemiology, risk factors, and clinical outcomes. To address this knowledge gap, we conducted a comprehensive analysis using the Nationwide Inpatient Sample (NIS) database to evaluate the epidemiology, prevalence, predictors, and clinical outcomes of ICH in adults with SCA. Methods: We conducted a retrospective cohort study using the NIS database from 2016 to 2020 to identify hospitalizations with SCA, using the ICD-10-CM (International Classification of Diseases, Tenth Revision, Clinical Modification) codes. Subsequently, we derived the prevalence and predictors of ICH in SCA adults. Results: Out of 468,070 admissions of adult hospitalizations (Aged ≥ 18 years) with SCA between 2016 and 2020 in the United States, 825 (0.17%) had ICH (nontraumatic intraparenchymal and/or subarachnoid bleeding). 410 (49.7%) were males, and 380 (46.0%) belonged to the age group of more than 45 years. The mean length of stay was 14.9 days, and 210 deaths occurred during the index hospitalization, resulting in a 25.4% inpatient mortality rate as compared to 0.6% in SCA-non-ICH patients (p < 0.001). Across all adult SCA hospitalizations during 2016–2020 (n = 468,070), ICH accounted for 210 of 2940 inpatient SCA deaths (7.1%). On multivariate logistic regression analysis, hypertension (OR:2.08, 95% CI: 1.2–3.3), prior history of ischemic stroke (OR: 17.06, 95% CI: 7.5–38.5), and a Charlson comorbidity index of more than one (OR: 2.9, 95% CI: 2.4–3.5) are significant predictors of ICH in adults with SCA. Conclusions: This study highlights the high prevalence of ICH in addition to the well-known thrombotic phenomenon among SCA patients. Stroke prevention and hypertension control are of paramount importance for the prevention of this catastrophic event in patients with SCA. Full article

Bladder dysfunction, particularly overactive bladder (OAB), is increasingly recognized as a clinical concern in patients with sickle cell disease (SCD), yet its pathophysiological mechanisms remain poorly understood. This study investigated the relationship between oxidative stress, inflammation, and bladder dysfunction in the Townes transgenic SCD mouse model. Cystometric analysis revealed that SCD mice exhibit an OAB phenotype, characterized by increased frequencies of voiding and non-voiding contractions and reduced bladder compliance. In vitro functional assays demonstrated detrusor hypocontractility in SCD mice, associated with a significant reduction in carbachol- and EFS-induced contractions and downregulation of muscarinic M3 receptor expression. Purinergic signaling and calcium-dependent contractility remained preserved. Molecular analyses showed increased mRNA expression of NOX-2 and IL-1β, and elevated protein levels of 3-nitrotyrosine and myeloperoxidase (MPO) activity, indicating redox imbalance and chronic inflammation in bladder tissue. Together, these changes suggest that oxidative and nitrosative stress, combined with inflammation, contribute to bladder remodeling and dysfunction in SCD. This is the first study to characterize bladder alterations in Townes SCD mice, establishing this model as a valuable tool for investigating lower urinary tract complications in SCD. Our findings provide mechanistic insight into the genitourinary manifestations of SCD and identify redox and inflammatory pathways as potential therapeutic targets for bladder dysfunction in affected individuals. Full article

Priapism is a frequent and debilitating complication in patients with sickle cell disease (SCD), characterized by recurrent ischemic episodes that can culminate in fibrosis of the erectile tissue and irreversible erectile dysfunction. Despite significant advancements in the management of acute episodes, current therapies remain largely ineffective in preventing recurrences, emphasizing the need for novel strategies that target the underlying pathophysiology. This narrative review describes the mechanistic links between oxidative stress and nitric oxide (NO) dysregulation in the pathogenesis of SCD-associated priapism, with a particular focus on the NO–cyclic guanosine monophosphate (cGMP)–phosphodiesterase type 5 (PDE5) signaling axis. We analyze preclinical evidence supporting resveratrol, a natural polyphenolic compound, as well as its NO-donor hybrid derivatives, as emerging therapeutic candidates. Additionally, we discuss the potential of combining resveratrol with current treatment approaches, and address the translational challenges that must be overcome to move from preclinical data to clinical application. Taken together, the evidence presented in this review supports resveratrol-based therapies as a promising approach for oxidative-stress-driven priapism in SCD and delineates critical perspectives for their further investigation. Full article

Background: Sickle cell disease (SCD) is a hereditary hemoglobinopathy associated with life-threatening complications such as acute chest syndrome (ACS), which may necessitate extracorporeal membrane oxygenation (ECMO) in refractory cases. Despite growing use, ECMO in SCD remains challenging due to risks of hemolysis, thrombosis, and anticoagulation complications. This systematic review consolidates existing evidence on ECMO outcomes in SCD, focusing on indications, complications, and survival. Methods: A systematic search of MEDLINE, Cochrane CENTRAL, and Google Scholar was conducted up to January 2025, identifying case reports/series on ECMO use in SCD. Studies reporting venovenous (VV) or venoarterial (VA) ECMO for acute cardiopulmonary failure were included. Data on demographics, laboratory findings, management, and outcomes were extracted. Quality assessment was performed using the Joanna Briggs Institute checklist. Results: Sixteen case reports (23 patients) were included. Most patients were female (65.2%), with ACS (47.8%) and pulmonary embolism (13.0%) as common ECMO indications. VV-ECMO (69.6% of cases) was primarily used for respiratory failure, with a 69% survival rate, while VA-ECMO (30.4%) had a 29% survival rate, often due to cardiogenic shock or cardiac arrest. Complications included hemorrhage (26.1%), neurological injury (21.7%), and thrombosis (13.0%). Exchange transfusion was frequently employed (43.5%), with post-ECMO echocardiography showing improved right ventricular function in survivors. Conclusions: VV-ECMO demonstrates favorable outcomes in SCD-related respiratory failure, whereas VA-ECMO carries higher mortality risks. Careful patient selection, anticoagulation management, and multidisciplinary coordination are essential. Larger prospective studies are needed to refine ECMO utilization in this high-risk population. Full article

Background: Patients with sickle cell disease (SCD) experience severe and life-threatening complications over their lifespans. However, research on SCD age-related complications is limited. Objective: This study examined differences in the number and type of SCD-related complications by age group among Texas Medicaid pediatric patients, and the factors associated with salient complications. Methods: This retrospective study used Texas Medicaid prescription and medical claims (2012–2021). Subjects aged 2 to 18 years, with ≥3 SCD hospitalizations or outpatient visits, and continuously enrolled for ≥12 months after the first SCD diagnosis claim were included. Complications were characterized by number and type of organ systems affected. Sociodemographic and clinical factors were used as potential factors associated with the most salient complications. Descriptive and inferential (ANOVA, Chi-square, and multivariable logistic regression) analyses were employed. Results: The included 1555 patients (mean age = 9.5 ± 5.1) were categorized into four age groups: 2–4 (23.4%), 5–9 (26.9%), 10–14 (27.4%), and 15–18 (22.3%) years. Documented number and type of complications differed significantly (all p < 0.0001) by age group, with the 2–14 years group having more documented complications compared to the 15–18 years group. Neurological complications were most common (~65%), followed by infections (~42%), and cardio-pulmonary complications (~30%). Young age group, hydroxyurea use, and having mental health comorbidities were associated with greater likelihood of experiencing vaso-occlusive crises, respiratory infections, and acute chest syndrome. Conclusions: Patterns of SCD-related complications (e.g., VOCs, respiratory infections, and acute chest syndrome) differ significantly by age group, leading to increased morbidity and acute care utilization. Despite its reported association with better outcomes, hydroxyurea utilization was found to be poor, with only 16% of patients receiving it for at least 180 days annually. Access to appropriate healthcare and improved utilization of hydroxyurea are needed to improve health outcomes of this population over their lifespan. Full article

Background: The coexistence of sickle cell disease (SCD), vascular Ehlers–Danlos syndrome (vEDS), primary ciliary dyskinesia (PCD), and Phelan–McDermid syndrome (PMS) in a single pediatric patient is extremely rare and poses substantial diagnostic and management challenges. Case presentation: We report an 8-year-old male from Jazan, Saudi Arabia, born to consanguineous parents, with early-onset SCD, followed by the identification of vEDS, PCD, and PMS through clinical presentation and whole exome sequencing. His disease course has been exceptionally severe, marked by monthly hospitalizations, multiple PICU admissions, and a wide spectrum of systemic complications. Conclusions: The coexistence of SCD, vEDS, PCD, and PMS may lead to synergistic vascular, pulmonary, and neurodevelopmental compromise, demanding multidisciplinary long-term management. This case underscores the need for a comprehensive targeted genetic assessment in patients with unusually aggressive or syndromic SCD phenotypes, particularly in regions with high levels of consanguineous marriages. Full article

Sickle cell disease (SCD) is a hereditary hemoglobin disorder characterized by chronic hemolysis and recurrent vaso-occlusive crises, leading to a wide spectrum of complications. While common SCD manifestations have well-established management protocols, rare and atypical complications pose significant diagnostic and therapeutic challenges. A critical barrier is diagnostic overshadowing, where common SCD symptoms (pain, fever, respiratory distress) mask infrequent but life-threatening conditions, resulting in delayed recognition and suboptimal outcomes. This narrative review synthesizes the literature from 2000–2025 on rare SCD complications, including atypical neurological events (e.g., spontaneous epidural or subdural hematoma, central retinal artery occlusion, cerebral arteriovenous malformations, posterior reversible encephalopathy syndrome), uncommon hematologic syndromes (acute leukemia, extramedullary hematopoiesis in unusual sites, hemophagocytic lymphohistiocytosis), severe cardiopulmonary emergencies (acute multiorgan failure and fat embolism syndromes), unusual hepatic crises (acute hepatic sequestration, intrahepatic cholestasis), and others (e.g., compartment syndrome). Key insights underscore the need for high clinical suspicion and prompt use of advanced diagnostics (e.g., MRI, specialized laboratory tests) when patients present with atypical or disproportionate symptoms. Clinical implications: Heightening clinician awareness of these rare complications and implementing structured diagnostic strategies can facilitate earlier intervention, improving outcomes and reducing the high morbidity and mortality associated with these infrequent but severe events. Full article

Background: Quality care of individuals with sickle cell disease (SCD) is dependent upon education of the providers on their care team. Previous studies demonstrate lack of resident and provider comfort regarding care of patients with SCD, yet none have assessed these in medical students. Objective: This study aims to evaluate the adequacy of the research instrument for measuring medical students’ knowledge, confidence, and comfort regarding SCD and related complications prior to wider distribution. Methods: A self-assessment survey was distributed to medical students at two universities to evaluate their knowledge, confidence, and comfort in general SCD topics, in all clinical settings, and regarding common complications. Results: Of the 98 responses, knowledge (p < 0.001) and confidence (p = 0.02) were significantly different between topics, including epidemiology and genetics, pathophysiology, and treatment options. For “treatment options”, there were significant differences in knowledge (p = 0.02) and confidence (p = 0.02) between medical students at different levels of training. Students felt least knowledgeable and least comfortable with care of pregnant women and most knowledgeable and most comfortable with acute pain management. Caring for patients with specific SCD-related conditions increased knowledge and comfort across all domains. Conclusions: This instrument was adequate for measuring knowledge, confidence, and comfort in caring for those with SCD across all clinical settings. We identified a lack of knowledge, confidence, and comfort regarding treatment for those with SCD starting early in medical careers, which improves after caring for patients with various complications. Thus, educating and providing SCD patient experiences is crucial for medical student management confidence related to SCD. Full article

Microfluidic methods are an important tool for studying the microrheology of blood and the mechanical properties of blood cells—erythrocytes, leukocytes, and platelets. In patients with diabetes, hypertension, obesity, sickle cell anemia, or cerebrovascular or peripheral vascular diseases, hemorheological alterations are commonly observed. These include increased blood viscosity and red blood cell (RBC) aggregation, along with reduced RBC deformability. Such disturbances significantly contribute to impaired microcirculation and microvascular perfusion. In blood vessels, abnormal hemorheological parameters can elevate resistance to blood flow, exert greater mechanical stress on the endothelial wall, and lead to microvascular complications. Among these parameters, erythrocyte deformability is a potential biomarker for diseases including diabetes, malaria, and cancer. This review highlights recent advances in microfluidic technologies for in vitro assays of RBC deformability and aggregation, as well as leukocyte aggregation and adhesion. It summarizes the core principles of microfluidic platforms and the experimental findings related to hemodynamic parameters. The advantages and limitations of each technique are discussed, and future directions for improving these devices are explored. Additionally, some aspects of the modeling of the microrheological properties of blood cells are considered. Overall, the described microfluidic systems represent promising tools for investigating erythrocyte mechanics and leukocyte behavior. Full article

Sickle cell disease (SCD) is a prevalent genetic disorder caused by a mutation in the beta-globin gene. Hyperhemolysis (HS) is a severe complication involving the rapid destruction of both transfused and endogenous red blood cells, commonly found in SCD. This literature review explores the clinical presentation, diagnosis, pathogenesis, and management of HS in SCD. HS can manifest acutely or in a delayed manner, complicating diagnosis due to overlapping symptoms and varying reticulocyte responses. Immunohematological assessments often reveal delayed positivity in direct antiglobulin tests and antibody screens. HS typically presents severe anemia, jaundice, hemoglobinuria, and hemodynamic instability. Diagnostic markers include elevated bilirubin and lactate dehydrogenase levels alongside a reduced reticulocyte count. The management of HS is primarily empirical, with no clinical trials to support standardized treatment protocols. First-line treatments involve steroids and intravenous immunoglobulins (IVIG), which modulate immune responses and mitigate hemolysis. Refractory cases may require additional agents such as rituximab, eculizumab, tocilizumab, and, in some instances, plasma exchange or erythropoietin-stimulating agents. Novel therapeutic approaches, including bortezomib and Hemopure, have shown promise but require further investigation. Current management strategies are empirical, underscoring the need for robust clinical trials to establish effective treatment protocols that ultimately improve outcomes for SCD patients experiencing HS. Full article

Background: PP-007 (SANGUINATE^®, PEGylated carboxyhemoglobin, bovine) is under development to treat conditions of ischemia/hypoxia. Hemorrhagic/hypovolemic shock (H/HVS) becomes a life-threatening comorbidity due in part to hypotension and hypoxia. Blood transfusions are indicated, but supply and compatibility issues may limit subject access or when blood is not an option due to religious restriction or concern for clinical complications. PP-007 is universally compatible with an effective hydrodynamic radius and colloidal osmotic pressure facilitating perfusion without promoting extravasation. Methods: A review of previous clinical trials was performed and revealed an Open-Label Phase 1 safety study of acute severe anemia (hemoglobin ≤ 5 g/dL) in adult (≥18 y) patients unable to receive red blood cell transfusion (NCT02754999). Primary outcomes included safety events with secondary efficacy measures of organ function and survival at 1, 14, and 28 days. Additionally, a retrospective review of published, peer-reviewed case reports was performed, evaluating the administration of Sanguinate for Expanded Access in those patient populations where blood was not an option over the past 12 years. Results: A total of 103 subjects were enrolled in the Phase I safety study with significant co-morbidities that most commonly included hypertension (n = 43), acute and chronic kidney disease (n = 38), diabetes mellitus (n = 29), gastrointestinal bleeds (n = 18), and sickle cell disease (n = 13). Enrollment characteristics included decreased hemoglobin and severe anemia (mean baseline hemoglobin of 4.2 g/dL). Treatments included an average of three infusions [range 1–17]. Secondary efficacy measures were mean Hb levels, respiratory support, and vasopressor requirements, all demonstrating clinically relevant improvements. Fourteen additional cases were identified in the literature. Though one patient died due to pre-treatment conditions, all patients but one were discharged home in stable condition. Conclusion: Collectively, these observations are encouraging and provide support for the continued evaluation of PP-007 in advanced clinical trials in severe anemia including H/HVS. The review of published case reports underscored the potential of Sanguinate to reduce early mortality. Adverse effects included transient hypertension, lethargy, dizziness, and troponin elevation. These findings highlight the need for continued research and funding of blood alternatives to improve outcomes when standard blood transfusions are unavailable or contraindicated. Full article

Background: Sickle cell disease (SCD) is associated with high physical and psychosocial burden among patients and their families. Hydroxyurea (HU) improves health-related quality of life by preventing SCD complications. Despite its availability, HU is underutilised in Tanzania. Perceived self-efficacy for appropriate medication use influences medication usage among individuals with chronic illnesses. We studied factors associated with caregivers’ perceived self-efficacy for appropriate use of HU and its association with HU usage among children with SCD in Dar-es-Salaam. Methods: We conducted a cross-sectional study from May to August 2023. We enrolled 374 caregivers of children with SCD from two regional and two national hospitals. We adapted the self-efficacy for appropriate medication use scale, a multidimensional perceived social support scale, and a patient health questionnaire for assessment of self-efficacy, social support, and depressive symptoms, respectively. Results: Three-quarters of caregivers had high perceived self-efficacy scores for medication use. Attending national hospitals, high social support, and absence of depressive symptoms were positively associated with perceived self-efficacy (adjusted beta coefficient aβ 2.3, 95% CI 0.5–4.2; aβ 9, 95% CI 7.1–10.9; and aβ 5.3, 95% CI 2.8–7.8, respectively). Caregivers with high self-efficacy were 5.3 times more likely to give HU to their children compared with those with low self-efficacy (incidence rate ratio 5.3, 95% CI 3.3–8.3). Conclusions: Hospital levels and psychosocial factors influence caregivers’ perceived self-efficacy for appropriate HU use. We recommend targeted interventions to enhance psychosocial support among caregivers to increase caregivers’ perceived self-efficacy and HU utilization among children with SCD in Tanzania. Full article