Search Results (660)

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/Objectives: Childhood anemia remains a serious public health issue, negatively affecting cognitive and psychomotor development, with repercussions on school performance and adult productivity. This study aimed to characterize the profile of children aged 6 months to 5 years diagnosed with or at risk of anemia who attended a pediatric hospital in Lisbon, Portugal. Methods: A hospital-based, cross-sectional descriptive study was conducted from September 2023 to September 2024. Descriptive statistics, including frequency distributions and cross-tabulations, summarized participant characteristics and key variables. Results: We observed that 33.3% (74/222) of the children were either anemic or at risk of anemia. Among these, 93.2% (69/74) were confirmed anemic or at risk based on hemoglobin levels. Five children (6.8%) had normal hemoglobin but abnormal red-cell indices, with microcytic (60.0%; 3/5) or normocytic (40.0%; 2/5) patterns. Anemia rates were higher in males (55.1%), children aged 24–59 months, those residing in the Metropolitan Lisbon Area (82.6%), children whose caregivers had only basic or secondary education (58.0%), and those whose mothers were born in foreign countries (48.4%). Microcytic red-cell indices were observed in 63.1% of cases. Serum iron results indicated that 32.0% were pre-anemic and 40.0% anemic. Ferritin levels showed iron-deficiency anemia in 22.2% of tested cases. In addition, 33.3% carried the sickle cell trait, and 35.0% had elevated C-reactive protein, suggesting anemia of inflammation. Conclusions: Anemia is a moderate public health issue, mainly affecting children with less-educated caregivers and migrant mothers. Targeted public health actions, including systematic screening, caregiver education, and multiculturally sensitive interventions, are crucial to address anemia. 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

Sickle cell disease (SCD) affects millions globally, with approximately 0.26% of the Saudi population impacted. Despite standard treatments, patients frequently experience vaso-occlusive crises (VOCs). This retrospective observational study evaluated the real-world effectiveness of L-glutamine (Endari^®) in reducing SCD-related complications in the Saudi population, where data remain limited. Patients aged five and older who received L-glutamine from June 2019 to June 2023 were included. The primary endpoint was VOC frequency through week 48. Descriptive statistics and paired t-tests compared outcomes before and after treatment. Fifteen patients (median age 12 years, 53% female) met the inclusion criteria; all were on maximum tolerated hydroxyurea. Eleven completed 48 weeks, showing a median VOC reduction from 4 to 3 (p = 0.44). Hospital stay duration remained unchanged (median 7 days, p = 0.72). Laboratory parameters were largely stable, except for a 61.9% increase in reticulocyte count (p = 0.03). The estimated annual treatment cost exceeded SAR 2 million (USD ~547,840). L-glutamine did not produce statistically significant improvements in VOC frequency, though numerical trends were observed. Given the small sample size and limited statistical power, the findings are exploratory. Larger, well-powered, multicenter studies are needed to confirm L-glutamine’s potential benefits in this population. Full article

Sickle-cell disease (SCD) is a group of inherited blood disorders in which a mutation in the β-globin (HBB) gene causes red blood cells to produce abnormal hemoglobin, known as Hb S. SCD is characterized by an autosomal-recessive pattern of inheritance, implying that for a child to manifest the condition, they must inherit an Hb S allele from both parents (HbSS) or one Hb S allele and another β-globin variant, such as Hb C or β-thalassemia (HbSC, HbS/β-thal). It has been observed that (heterozygote) carriers of one copy of the sickle-cell trait (HbAS) are typically healthy and can even gain partial protection from severe malaria. The term “severe and complicated malaria” is delineated based on specific clinical and laboratory characteristics in the presence of Plasmodium falciparum parasitemia. The prevalent forms of severe malaria among African children include cerebral malaria, respiratory distress, and severe malaria anemia. Cerebral malaria is a rare complication of malaria infection and is associated with a high mortality rate. Full article

Testicular orphan receptors TR2 and TR4 serve as central regulators of erythropoiesis, orchestrating the entire continuum of erythroid progenitor cell proliferation, differentiation, and maturation. As core components of the direct repeat erythroid determinant (DRED) complex, they activate erythroid-specific transcriptional programs to dynamically control the spatiotemporal expression of globin genes. These nuclear receptors not only engage in functional interactions with key erythroid transcription factors GATA1 and KLF1 to coregulate erythroid differentiation and maturation but also recruit epigenetic modifier complexes such as DNMT1 and LSD1 to modulate chromatin states dynamically. Research has established that dysfunctions in TR2/TR4 are implicated in β-thalassemia and sickle cell disease (SCD): β-thalassemia is associated with the defective silencing of γ-globin genes, while in SCD, TR2/TR4 antagonizes BCL11A to reactivate fetal hemoglobin (HbF) expression. This review systematically dissects the molecular regulatory networks of TR2/TR4 in erythroid cells, interprets their dual regulatory properties across different stages of erythroid differentiation, and explores the therapeutic potential of targeting TR2/TR4 for treating erythroid-related disorders such as β-thalassemia and SCD, thereby providing novel directions for hematological disorder therapy. Full article

Background/Objectives: Sickle cell disease (SCD) is caused by a β-globin gene mutation (βGlu6Val) that produces sickle hemoglobin (HbS). When deoxygenated, HbS polymerizes, leading to red blood cell (RBC) sickling; therefore, hemoglobin is a central therapeutic target for SCD. Current strategies include increasing the levels of oxygenated HbS (which cannot polymerize) and/or directly destabilizing the deoxygenated HbS polymer. This study aimed to design and synthesize next-generation Michael acceptor antisickling hemoglobin modifiers (MMA-206, MMA-207, MMA-208, and MMA-209) and evaluate their antisickling efficacy. Methods: Four Michael acceptor compounds (MMA-206 to MMA-209) were synthesized and characterized. Their pharmacologic activities and modes of action were assessed in vitro using disulfide exchange reaction with normal hemoglobin, sickling inhibition assays with sickle red blood cells, and hemoglobin oxygen equilibrium curve analysis with normal and sickle red blood cells. Results: MMA-206 exhibited the strongest antisickling activity, outperforming previously studied Michael acceptor antisickling agents. All four MMA analogues bound to hemoglobin at βCys93, destabilizing the low-oxygen-affinity T-state and thereby preventing deoxygenation-induced HbS polymerization and RBC sickling. In addition, they appeared to directly destabilize the HbS polymer, indicating a second mechanism of action. Furthermore, time-dependent oxygen equilibrium measurements confirmed that their pharmacologic effect was sustained over time in vitro. Conclusions: The new Michael acceptor compounds, particularly MMA-206, demonstrated potent antisickling effects via dual mechanisms and showed sustained activity. These findings highlight Michael acceptor compounds’ promise as hemoglobin oxygen-affinity modulators for the treatment of SCD. Full article

Sickle cell disease (SCD) is a common genetic disorder affecting up to 2.6% of the population in Saudi Arabia. SCD results in severe disability, reduced quality of life, extensive use of medical resources, increased economic burden, and a high likelihood of increased mortality. Red blood cell transfusion remains a cornerstone in the management of SCD complications. This position paper highlights the current state of SCD management within the Kingdom of Saudi Arabia. Despite the advantages of automated red blood cell exchange (aRBCX) and guideline recommendations, its use remains limited. In practice, aRBCX is used for a variety of indications, including acute management and prophylaxis of stroke, systemic fat embolism, severe forms of acute chest syndrome, preoperative management, hematopoietic stem cell transplantation, hepatic crisis, and priapism. However, aRBCX is underutilized in pregnancy. Common gaps identified by the advisory panel include the absence of standardized national guidelines, limited access to aRBCX, issues with vascular access, lack of equipment, and insufficient staff training. Another limitation to the use of aRBCX is the higher blood requirements compared to other blood transfusion modalities. These factors contribute to geographical disparities in the management of SCD and suboptimal patient outcomes. To address these issues, the advisory panel recommended developing and implementing evidence-based national guidelines, expanding access to aRBCX, enhancing health staff education and training, and establishing a robust national SCD registry. By prioritizing these recommendations, we can help streamline SCD care, reduce practice variation, and nationalize sickle cell disease management in Saudi Arabia to improve patient care. Full article

Background/Objectives: Despite the high incidence of sickle cell anemia in Saudi Arabia, little is known about the sociodemographic characteristics, behavioral risk factors, and concomitant conditions of the condition. We performed this study to measure the prevalence of sickle cell anemia and its associated predictors among Saudi residents. Methods: This cross-sectional study was conducted in 48 primary healthcare centers across Saudi Arabia. A total of 14,239 Saudi residents were included through multi-stage random sampling. Data on sociodemographic variables, behavioral factors, and comorbidities were collected using a validated and reliable questionnaire. Univariate and multivariate logistic regression analyses were performed to identify the predictors of sickle cell anemia, with the statistical significance set at a p-value of <0.05. All analyses were carried out using SPSS version 26 for Windows. Results: Overall, the prevalence of sickle cell anemia was found to be 3.2% among Saudi residents. There was a positive association between insurance coverage and sickle cell anemia (AOR: 1.87; 95% CI: 1.52, 2.31). The odds of sickle cell anemia were 1.39 times higher among diabetic than non-diabetic individuals (AOR: 1.39; 95% CI: 1.01, 1.91). There were positive associations between sickle cell anemia and hypertension (AOR: 1.70; 95% CI: 1.23, 2.35), high cholesterol (AOR: 2.38; 95% CI: 1.74, 3.24), and heart disease (AOR: 8.05; 95% CI: 6.05, 10.71). Conclusions: Our findings indicate significant associations between sickle cell anemia and insurance coverage, smoking, obesity, diabetes mellitus, hypertension, hypercholesterolemia, and heart disease. While the overall prevalence of sickle cell anemia in our study was relatively modest, the Saudi Arabian government should prioritize the objective quantification of the disease burden across the population to effectively mitigate its consequences. Full article