Search Results (589)

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

Hemophilias and hemoglobinopathies—including hemophilias A and B, sickle cell disease (SCD), and β-thalassemia—are debilitating genetic disorders associated with significant global health burdens. While traditional management has centered on factor replacement and transfusions, these approaches remain palliative, with limited access and durability in many regions. Recent advances in immune-based therapeutics (e.g., emicizumab, concizumab, crizanlizumab), viral vector-mediated gene addition (e.g., Roctavian, Hemgenix), and gene-modified autologous stem cell therapies (e.g., Zynteglo, Casgevy) have ushered in a new era of disease-modifying and potentially curative interventions. These therapies offer durable efficacy and improved quality of life, particularly in adult populations. However, implementation remains uneven across global health systems due to high costs, limited infrastructure, and regulatory heterogeneity. Additionally, ethical considerations such as long-term surveillance, informed consent in vulnerable populations, and social perceptions of genetic modification present ongoing challenges. Innovations such as multiplex genome editing, immune-evasive donor platforms, synthetic biology, and AI-driven treatment modeling are poised to expand therapeutic horizons. Equitable access, particularly in regions bearing the highest disease burden, will require collaborative funding strategies, regional capacity building, and inclusive regulatory frameworks. This review summarizes the current landscape of curative therapy, outlines implementation barriers, and calls for coordinated international action to ensure that transformative care reaches all affected individuals worldwide. Full article

Objectives: Sickle Cell Disease (SCD) has a significant impact on the musculoskeletal system. The use of the Oxford Hip (OHS) and Shoulder score (OSS) as patient-reported outcome measures (PROMs) revealed a high rate of long-term impairment in joints with a pre-existing diagnosis of avascular necrosis (AVN). With this study, we aimed at detecting dysfunction in joints apparently not affected by AVN. Methods: This is a subgroup analysis of a previous core study assessing the OHS and OSS in 47 SCD patients with a pre-existing diagnosis of AVN. For this study, only patients with a pre-existing diagnosis of isolated AVN (only hip or only shoulder) were selected, and the OHS or OSS was measured in previously unaffected joints. Results: Among 37 patients with isolated AVN, 19 (51%) patients presented abnormal scores in the apparently unaffected joint; 16 (50%) patients with pre-existing isolated hip AVN had an abnormal OSS; and 9 (56%) had moderate to severe shoulder impairment. All patients with pre-existing isolated shoulder AVN had an abnormal OHS, with severe hip impairment in two out of three. As per clinical practice, patients with an abnormal score were prescribed joint magnetic resonance imaging (MRI) and/or X-rays. Only 10 out 19 (53%) performed imaging studies and all showed signs of AVN. Conclusions: Abnormal OHS and OSS values indicated a high rate of joint dysfunction in sites apparently not affected by AVN. The routine use of these PROMs should be applied to all SCD adults and subjects with a pathological score should have priority access to diagnostic radiological tests. Full article

Background and Objectives: Hemoglobinopathies are genetic disorders of hemoglobin and are among the most common inherited diseases. The prevalence rates of sickle cell disease and thalassemia in Saudi Arabia are higher than those in other countries in the Middle East. Saudi Arabia has launched many prevention programs such as a premarital screening program, genetic counseling programs, and neonatal screening in order to reduce the incidence of genetic diseases. The former program includes the most common genetic diseases: sickle cell disease and thalassemia. Many studies conducted since the premarital program started have reported a decrease in the prevalence of sickle cell disease and thalassemia. However, all studies focus on large cities, including their subdivisions, but there is a lack of studies on subdivisions specifically. Materials and Methods: The aim of this study was to assess the prevalence, 5-year time trend, and distribution of β-thalassemia and sickle cell traits in Al-Kharj province using the data of the PMSGC program during the period from January 2017 to February 2021. Results: A total of 21,150 individuals were screened, and 508 were diagnosed with sickle cell disease and thalassemia. Also, we showed that thalassemia was more prevalent than sickle cell disease (66% and 34%, respectively), and there was an increase in β-thalassemia and α-thalassemia. Conclusions: Riyadh city’s prevalence rate of β-thalassemia was reported as 7 per 1000, while the current study found a prevalence rate of 5.6 per 1000 in Al-Kharj, which suggests a possible increase as a result of population growth in Al-Kharj province as part of Riyadh city. This study recommends further improvement in preventive measures in high-risk regions, as well as enhanced community awareness, to provide the highest rate of reduction for disorders. Full article

Background: Hydroxyurea is approved for the treatment of paediatric and adult sickle cell disease patients. It causes the synthesis of foetal haemoglobin and decreases platelets and granulocytes, but with a high interindividual variability, requiring higher dosages and escalating toxicity. Hereditary variables should be investigated to personalise treatment. We evaluated the possible influences of OCT1 and MAP3K5 gene polymorphisms on hydroxyurea pharmacokinetics. Methods: We conducted a retrospective analysis on 79 treated patients. The polymorphisms of OCT1 (rs683369 G > C) and MAP3K5 (rs9376230 C > A and rs9483947 C > T) were genotyped. Results: Sub-Saharan patients with the OCT1 rs683369 GG genotype showed a lower drug half-life, compared to those with the GC genotype. In sub-Saharan paediatric female patients, the OCT1 rs683369 GG genotype was associated with a lower t1/2 than the GC genotype. Conclusions: The findings demonstrate for the first time how crucial it is to assess the pharmacogenetics of hydroxyurea by taking into account the two sexes in different groups. Additionally, the data were evaluated with consideration for ethnic groups and individually for adults and children. Pharmacogenetic studies could improve the clinical management of hydroxyurea. Full article

Hemoglobin (Hb) defects, or hemoglobinopathies such as thalassemia and structural Hb variants, are among the most prevalent inherited diseases and are associated with significant mortality and morbidity worldwide. Screening for hemoglobinopathies in the primary care setting plays a critical role in enhancing patient outcomes and advancing population health. It promotes awareness, enables early diagnosis and treatment, supports informed reproductive decisions through genetic counseling, and facilitates access to novel therapies such as genetic modifications. Screening approaches for hemoglobinopathies have evolved to reflect regional prevalence, healthcare infrastructure, and ethical considerations. Varying strategies underscore the necessity of tailoring to local contexts, balancing cost, accuracy, accessibility, and social impact. As global migration reshapes population genetics, flexible and equitable screening frameworks are increasingly essential. This review focuses on practical techniques suitable for the screening of Hb defects in primary care. Recent advances and findings in high-performance liquid chromatography, capillary zone electrophoresis, mass spectrometry, point of care testing, and molecular methodologies are covered. In addition, strategies and approaches in multiple regions in the world are reviewed. 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: One of the major challenges for children and adolescents with sickle cell disease (SCD) is academic performance. Objectives: Our study aimed to evaluate the academic performance of children and adolescents with SCD in Benin and compare it to the academic performance of their healthy siblings and paediatric comparisons. Furthermore, we aimed to explore the associations between socio-demographic factors, clinical characteristics, and depressive symptoms, and the academic performance of children and adolescents with SCD. Methods: The study was a cross-sectional study that used convenient sampling. Academic scores were collected during the 2021–2022 academic year. Patients with SCD and paediatric comparisons were recruited during routine hospital consultations. The Children’s Depression Inventory (CDI-S) tool was used to assess depressive symptoms. We compared academic performance scores (ranging from 0 to 20) using independent t-tests and explored associations through linear regression analyses. Results: This study included 209 participants: 100 patients with SCD (aged 6 to 17 years), 46 siblings, and 63 paediatric comparisons. The academic performance of patients with SCD (mean academic score = 13.29) was similar to that of the combined comparison group (mean academic score = 12.8, p = 0.196). Younger patients showed poorer academic performance (coef = −0.169, p = 0.019), and depressive symptoms (‘pessimism’, ‘self-hate’, ‘lack of friends’, and ‘fatigue’) were associated with poorer academic performance as well. Patients with SCD who were treated in Benin performed academically as well as their healthy siblings and peers. Conclusions: Children and adolescents with SCD performed on par academically with their healthy siblings and peers. While overall depressive symptoms were not significantly associated with academic performance, certain symptoms were more common among lower-performing students and should therefore be explored in greater detail. Full article

Sickle cell disease (SCD) is the most common hemoglobinopathy, caused by a mutation in the β-globin gene of hemoglobin. It predisposes patients to painful Vaso-occlusive crises (VOC) and multi-organ dysfunctions. The disease exhibits significant phenotypic variability, making it challenging to predict severity and outcomes. This study aimed to characterize the whole blood gene expression profile of Bahraini SCD patients, identifying differentially expressed genes during steady-state (n = 10) and VOC (n = 10) compared to healthy controls (n = 8). Analysis revealed 2073 and 3363 dysregulated genes during steady-state and VOC, respectively, compared to controls, with 1078 genes differentially expressed during VOC versus steady-state. Gene Ontology (GO) enrichment analysis highlighted significant deregulation in immune and hematopoietic pathways, including down-regulation of critical genes for immune modulation and hematopoietic balance. Notably, the transcription factor RUNX3, involved in immune cell differentiation and inflammation, was among the 668 down-regulated genes. RUNX3 was four-fold down-regulated in microarray analysis, three-fold in PCR, and showed a mean protein concentration of 11.13 pg/mL during VOC compared to 457.93 pg/mL during steady-state (p < 0.01). These findings suggest that RUNX3 may serve as a potential biomarker for VOC. Future large-scale validation, additional proteomic studies, and functional investigations are recommended to confirm its clinical utility and significance. 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/Objectives: Children with sickle cell disease (SCD) often experience limited access to care, contributing to poor health outcomes. Patient-level predictors and outcomes associated with telehealth use among Medicaid-enrolled children with SCD remain unknown. This study aims to (1) analyze telehealth trends before and during the pandemic (March 2020–March 2022), (2) identify patient-level predictors of telehealth use, (3) assess its association with care continuity and health outcomes, and (4) identify physician specialties involved in telehealth visits. Methods: Using Texas Medicaid claims (March 2017–March 2022), we conducted a retrospective analysis of children aged 1–18 with ≥3 SCD-related claims. Monthly trends in outpatient visits (in-person and telehealth) were visualized from March 2019 to March 2022. Multivariable regression models examined predictors of telehealth use and associations with ≥10 hydroxyurea fills, emergency department (ED) visits, and hospitalizations, adjusting for age, sex, regions with SCD clinics, and prior healthcare utilization. Results: Among 903 included patients (mean [SD] age = 10.4 [4.1], 52.6% male), 59.4% had ≥1 telehealth visits between March 2019 and March 2022. Telehealth use peaked between March 2020 and May 2020, then gradually declined. Children with ≥10 SCD-related outpatient visits 1 year before the lockdown (March 2019–February 2020) had 77.4% higher odds of using telehealth compared to those with 0–4 visits (OR = 1.774, 95% CI = 1.281–2.457, p = 0.0006), while controlling for sociodemographic characteristics. However, SCD-related telehealth use during the pandemic was not associated with either ≥10 hydroxyurea fills or reduced ED visits. Prior healthcare utilization remained a strong predictor of both outcomes. The majority of telehealth visits were conducted at multispecialty clinics (74%). Conclusions: Telehealth use surged early in the pandemic but later declined among Texas Medicaid-enrolled children with SCD. Children with high healthcare needs adopted telehealth, but this did not impact care continuity or extensive healthcare utilization. While maintaining telehealth access, other measures should be implemented to improve access and outcomes for this vulnerable population. 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

The aberrant localization of the mutated nucleophosmin (NPM1) protein in the cytoplasm is the hallmark of the development of acute myeloid leukemia (AML); the gene, located in the nucleolus, codes for a protein that normally shuttles between the nucleus and the cytoplasm of the normal hematopoietic cells. Patients harboring NPM1 mutations are diagnosed as having NPM1-mutated AMLs, which are types of leukemia with distinct clinical and laboratory characteristics. The essential diagnostics for investigating NPM1-mutated AMLs, the interactions with concomitant mutations affecting prognosis and the therapeutic interventions that the treatment of such patients requires are discussed in this review. Novel investigational agents in current clinical trials are also highlighted, along with the roles of exportin 1 (XPO1), menin-KMT2A inhibitors and immunotherapy in NPM1-mutated AMLs. This review focuses on critically evaluating the available data and aims to reveal the secrets of NPM1-mutated AMLs. Full article