We evaluated 18-month changes in pancreatic iron burden and its relationship with systemic iron balance and glucose metabolism in non-transfusion-dependent thalassemia (NTDT) patients.We retrospectively studied 32 non-transfused (NT) and 57 regularly transfused(RT) NTDT patients enrolled in the Extension-Myocardial Iron Overload in Thalassemia project. Iron overload (IO) was assessed by T2* magnetic resonance imaging and glucose metabolism by oral glucose tolerance test.At baseline, iron chelation therapy was administered in 40.6% of NT-NTDT and 98.2% of RT-NTDT patients. No significant overall changes in pancreatic iron burden were observed in either group. New-onset pancreatic IO occurred in 22.7% of NT and 35.3% of RT patients with normal baseline pancreatic T2* values. Longitudinal changes in pancreatic iron burden were not associated with age, serum ferritin, baseline liver iron concentration(LIC), or changes in LIC, but were inversely related to baseline pancreatic T2* values. In RT patients, pancreatic iron changes were not influenced by baseline glucose metabolism status. After adjustment for baseline pancreatic T2*, NT-NTDT patients showed a greater increase in global pancreatic T2* than RT-NTDT patients. This difference was more pronounced among patients with baseline pancreatic IO.In NTDT patients, pancreatic iron burden showed slow longitudinal changes that were primarily driven by baseline pancreatic iron status rather than systemic iron balance, with a more favorable evolution in non-transfused than in regularly transfused patients.
The need for compatible blood remains a persistent challenge to timely and safe transfusion support. Despite this, the stability and functional behavior of antigen-blocking strategies under storage and physiologically relevant conditions remain poorly understood, particularly regarding their stability during prolonged exposure to changing blood environments. This study evaluates a trispecific triabody designed to simultaneously target A, B, and Rh(D) antigens on red blood cells to block antigen recognition and prevent incompatibility-related hemagglutination. Triabody-coated RBCs were prepared through repeated incubation cycles and assessed for stability in incompatible plasma under storage (4 degrees C) and physiologically relevant temperatures (37 degrees C). Results showed that the triabody bound efficiently and reached saturation across tested blood groups. During storage at 4 degrees C, detachment remained minimal during early storage but increased after prolonged incubation, coinciding with declining pH and increased free hemoglobin. At 37 degrees C, triabody detached progressively, with anti-B dissociation occurring earlier than anti-A and anti-Rh(D), while differential stability was also observed during prolonged storage at 4 degrees C. Detachment showed a closer temporal association with pH decline than with ionic strength or free hemoglobin changes and was followed by hemagglutination in incompatible plasma. Triabody-coated RBCs maintained antigen blocking during early exposure but showed differential stability during prolonged incubation, supporting their potential to improve transfusion compatibility while highlighting the need for further in vitro optimization of triabody binding stability before in vivo validation.
Background: HbSS causes high early mortality in sub-Saharan Africa, but longitudinal data from semi-rural Francophone Central Africa remain scarce. Objective: To investigate clinical evolution and hospitalization determinants in homozygous sickle cell patients in semi-rural Gabon. Methods: An ambispective cohort study of 286 HbSS patients (156 retrospective, 130 prospective) was conducted at Franceville University Hospital. Biological profiles were modeled via principal component analysis (PCA), and hospitalization predictors were identified using multivariate Firth's penalized logistic regression with multiple imputation (MICE). Results: The predominantly pediatric cohort (median age: 9.5 years) had a 92.3% hospitalization rate. Vasoocclusive crises (57.0%) and fever (58.9%) drove emergency admissions, alongside anemic shock (12.9%). PCA separated chronic hemolytic severity (PC1) from acute rheological adjustments (PC2). Hospitalization risk was driven exclusively by acute clinical complications, showing no association with socio educational indicators. A significant admission reduction occurred during 2021-2023 (OR approximate to 0.23; p = 0.013) due to optimized local protocols. Conclusions: Acute complications overrode static social determinants at admission ("clinical supremacy"). Public health priorities must incorporate universal neonatal screening, expanded hydroxyurea access, transcranial Doppler surveillance, and school-based individualized care plans.
Sickle cell disease (SCD) presents substantial interindividual clinical variability that remains only partially explained by genotype, fetal hemoglobin (HbF), and co-inherited alpha-thalassemia. We investigated whether endogenous metabolites modulate the sickling tendency, independently of HbF. We analyzed 368 steady-state HbSS patients with oxygen gradient ektacytometry (Point of Sickling [PoS]) and untargeted metabolomics (DI-HRMS, 1309 metabolites). PoS was adjusted for HbF for ANOVA analysis (A-FDR p <= 0.05). Linear regression (lr) models were adjusted for HbF, age, alpha-thalassemia, Oxygenscan device, and hydroxyurea (lr-FDR p <= 0.05). 111 metabolites differed between adjusted-PoS groups, and 27 metabolites associated with PoS in lr. Seven metabolites overlapped across approaches. Increased sickling (higher PoS) positively correlated with glycolytic and pentose phosphate pathway intermediates, glyceraldehyde-3-phosphate (A-FDR <0.001), 2,3-DPG (A-FDR = 0.002; lr-FDR = 0.004), and ribulose-5-phosphate (A-FDR <0.001). RBC membrane remodeling markers, including carnitines (lr-FDR = 0.002), and oxidative stress and inflammation metabolites: glutathione disulfides (A-FDR = 0.001), acetylated citrulline (A-FDR < 0.001; lr-FDR = 0.009), spermidine (lr-FDR = 0.03), and acetylated tryptophan (A-FDR = 0.03; lr-FDR = 0.03), were also elevated in this group. Low PoS associated with downstream tryptophan metabolites (A-FDR < 0.001, 0.006), indicating inflammatory regulation. Overall, this study demonstrates that metabolic processes are associated with sickling tendencies independent of HbF, providing insights into SCD heterogeneity, identifying candidate metabolic pathways, and supporting current strategies to target glycolysis in SCD.
Background: Sitosterolemia is a rare autosomal recessive lipid metabolism disorder caused by pathogenic variants in ABCG5 or ABCG8 genes. Although classically associated with xanthomas and premature atherosclerosis, some patients may predominantly present with hematologic manifestations, leading to significant diagnostic challenges. Methods: We retrospectively analyzed seven genetically confirmed cases of sitosterolemia presenting primarily with hematologic abnormalities at a tertiary care hematology center. Clinical characteristics, hematologic parameters, peripheral smear findings, molecular genetic profile, treatment response, and long-term outcomes were evaluated. Results: The median age at presentation was 15 years (range: 6-17 years). All patients presented with anemia and splenomegaly, while thrombocytopenia was observed in six patients. Peripheral blood smear examination demonstrated stomatocytes and/or macrothrombocytes in a majority of cases. None of the patients had tendon xanthomas or overt dyslipidemic manifestations at presentation. Genetic analysis revealed pathogenic or likely pathogenic variants involving ABCG5 and ABCG8 genes, including homozygous and compound heterozygous mutations. Ezetimibe therapy along with dietary plant sterol restriction resulted in clinical improvement with rise in hemoglobin levels and reduction in hemolytic manifestations on follow-up. Conclusion: Sitosterolemia is an underrecognized but treatable cause of hemolytic anemia with macrothrombocytopenia. Careful peripheral smear examination demonstrating stomatocytes and giant platelets can provide an important diagnostic clue. Early recognition and targeted therapy can significantly improve clinical outcomes.
