Introduction The diagnosis of beta thalassemia trait is primarily based on an elevated HbA2 level (> 3.5%) measured by high‐performance liquid chromatography or capillary electrophoresis. Iron deficiency (ID) can influence HbA2 levels, raising concern about potential diagnostic misclassification, particularly in individuals with borderline HbA2 values. This study aimed to evaluate the effect of ID and its correction on HbA2 levels and the diagnosis of beta thalassemia trait. Methods A prospective interventional study conducted between June 2021 and June 2022 at a National Thalassemia Centre, Sri Lanka. Ninety‐two participants aged 12–57 years with low red cell indices (MCV ≤ 80 fL, MCH ≤ 27 pg) and HbA2 < 3.5% were included. All had serum ferritin < 30 ng/mL indicating ID. Hematological and iron parameters, including HbA2 levels, were assessed before and after 3 months of oral iron therapy. Comparisons were made between subgroups with serum ferritin levels of < 15 ng/mL and 15–30 ng/mL. Correlations between Hb, HbA2, ferritin, and other iron indices were also examined. Results A significant positive correlation was observed between Hb and HbA2 levels prior to treatment. Following iron therapy, HbA2 levels increased significantly in iron‐deficient individuals ( p < 0.001). In three of eight participants with borderline HbA2 levels, treatment raised HbA2 above the 3.5% diagnostic threshold. Conclusions Oral iron therapy significantly affects HbA2 levels in iron‐deficient individuals and may cause borderline values to cross the diagnostic threshold for beta thalassemia trait. Iron status should therefore be considered when interpreting HbA2 results in thalassemia screening.

Background Malaria remains a major global health burden, with red blood cell (RBC) polymorphisms conferring partial protection. However, the epistatic interactions among co‐inherited RBC polymorphisms are poorly understood. We aimed to characterise how epistatic interactions among malaria‐protective RBC polymorphisms modify risk across the infection‐to‐mortality spectrum in endemic populations. Methods We systematically searched seven databases, trial registries, preprint servers and grey literature sources for studies reporting multilocus genotype‐phenotype associations for P. falciparum malaria, with duplicates removed and records screened by title and abstract. Full‐text reports were assessed and data were extracted using a structured form, independently verified by two reviewers. Risk of bias was evaluated with a modified Newcastle–Ottawa Scale. Joint genotypes were compared against wild‐type references within each study, and single‐locus effects were collated to establish a multiplicative “no‐interaction” expectation. Observed joint effects were classified as synergistic, antagonistic, or indeterminate based on study‐specific thresholds. Results Ten studies met inclusion, yielding 18 joint‐genotype contrasts across eight polymorphism pairs. Nine contrasts (50%) were antagonistic, six (33%) indeterminate, and three (17%) synergistic. The most reproducible signal was the antagonism between HbAS and α + ‐thalassaemia. Similar negation was observed for HbAS + G6PD A − , CR1 Sl 2 + α + ‐thalassaemia, and G6PD A − + CYB5R3 T117S, although the findings were based on fewer and smaller strata. Synergy was rare and confined to haptoglobin 2‐1 + α + ‐thalassaemia and HbS allele carriers + G6PD A − . Certainty of evidence was low or very low for 14/18 contrasts owing to small dual carrier strata, hospital case‐control designs and heterogeneity in endpoints. Margin‐shift sensitivity analyses indicated that the predominance of antagonism and the direction of the main HbAS and α + ‐thalassaemia and CR1 Sl 2 + α + ‐thalassaemia were robust to reasonable changes in the departure thresholds. Conclusions In the limited and heterogenous literature on multilocus malaria resistance, statistical epistasis between malaria‐protective RBC polymorphisms is common and more often antagonistic than synergistic, although the certainty of evidence was generally low. These findings suggest polygenic risk models, vaccine efficacy analyses and transmission or gene‐drive models should account for prevalent multilocus genotypes and their interaction terms rather than assuming independent single‐locus effects. Larger harmonised cohorts coupled with CRISPR‐based mechanistic studies are needed to refine effect sizes and clarify the biological pathways underlying these statistical interactions.

Anemia is a frequent diagnosis in premature and critically ill infants and is caused by phlebotomy, which is essential for medical care. The severity of anemia often correlates with the acuity of illness. We recently showed that severe neonatal anemia causes a "leaky gut" in neonatal mouse pups by altering the structure and function of epithelial adherens junctions through decreased E-cadherin expression. We hypothesize that microtubules play a major role in maintaining adherens junction integrity. To test this hypothesis, C57BL/6 mice were subjected to timed phlebotomy between postnatal days (P) 2-10 to induce severe anemia (hematocrits 20%-24%). Microtubular assembly was evaluated by electron microscopy, quantitative real-time polymerase chain reaction (qRT-PCR), immunohistochemistry, and/or immunoblotting on intestinal tissues, Caco-2 intestinal epithelial-like cells, and colonic organoids. The electron micrographs showed loss of microtubules in the anemic intestine and disrupted intestinal epithelial microtubular assembly. Microtubular disruption was associated with decreased expression of the α-tubulin 4a (tuba4a) subunit. The observed ultrastructural changes that disrupt epithelial barrier functions result from hypoxia-induced microRNA let-7e destabilizing tuba4a expression in the anemic intestinal epithelium. In conclusion, phlebotomy-induced anemia in mouse neonates is associated with a "leaky gut" by the disruption of microtubular assembly.

Sickle cell disease (SCD) is a major public health concern in Africa. SCD healthcare expenses are covered by personal finances in the Congo due to the absence of universal public health insurance. Various strategies have been implemented to minimize this economic burden, including an outpatient management strategy. The present study evaluated the costs associated with outpatient management of uncomplicated sickle cell crises. Patients presenting to the National Sickle Cell Center’s emergency room between December 2023 and February 2024 were included in this study for a total of 114 subjects with uncomplicated crises from SCD. Chief complaint, diagnosis, treatment, health insurance coverage, and cost of care were recorded for each subject. We further assessed the consistency of treatment with published standards of care. Mean patient age was 16 ± 13 years, where more than one‐third were adults (36.5%). The ratio of males to females was 1.09. Only 26.2% were employed. Monthly income was lower in individuals with SCD ($310.32 ± 120.93) compared to those without SCD ($386.92 ± 471). Managing uncomplicated SCD as an outpatient costs an average of $99.86 ± 49, where medications represented 55.7% of the total expense. Sixty‐six patients (57%) received prescription medications and investigation with no rational basis, resulting in an inflated cost of $15.96 per person. The present study did not demonstrate any financial benefits to managing uncomplicated SCD in outpatient settings.

IntroductionThalassemia trait generally has minimal clinical impact, but physiologic changes during pregnancy may increase the risk of anemia, transfusion requirements, and hypertensive disorders. Existing evidence on pregnancy outcomes in this population is limited, with some conflicting data. This study aims to evaluate pregnancy‐related outcomes in patients with thalassemia trait using a large, multicenter database.MethodsFor this retrospective cohort study, we used data from the TriNetX US Collaborative Network. Females aged 18–45 with ICD‐10 codes indicating pregnancy (Z33.1, O00–O9A, Z34, or Z3A) were included. Patients with pregnancy and coexisting thalassemia trait (D56.3) were assigned to the thalassemia cohort (n = 22,913), while those without any thalassemia diagnosis comprised the nonthalassemia cohort (n = 5,611,147). Propensity score matching was performed to balance age, race/ethnicity, obesity, smoking status, essential hypertension, and Type 2 diabetes mellitus. After 1:1 matching, 22,770 patients remained in each cohort (total N = 45,540). Outcomes were assessed within 1 year of the index date, including anemia during pregnancy, blood transfusion, preeclampsia/eclampsia, cesarean delivery, venous thromboembolism (VTE), heart failure/cardiomyopathy, preterm delivery, intrauterine growth restriction (IUGR), and intrauterine fetal demise (IUFD). Risk ratios (RRs) with 95% confidence intervals (CIs) were calculated.ResultsThalassemia trait was associated with higher risks of anemia during pregnancy (RR: 3.00 and 95% CI: 2.87–3.13), needing blood transfusion (RR: 1.90 and 95% CI: 1.69–2.20), preeclampsia/eclampsia (RR: 1.54 and 95% CI: 1.47–1.61), cesarean delivery (RR: 1.43 and 95% CI: 1.36–1.51), preterm delivery < 37 weeks (RR: 1.40 and 95% CI: 1.31–1.65), and IUGR (RR: 1.96 and 95% CI: 1.72–2.23), all were statistically significant with a p < 0.001. Increased risk was also observed for VTE (RR: 1.57 and 95% CI: 1.12–2.20, p < 0.001) and IUFD (RR: 1.37 and 95% CI: 1.087–1.75, p < 0.001). No significant association was found with heart failure/cardiomyopathy (RR: 1.28 and 95% CI: 0.93–1.76, p = 0.124).ConclusionThalassemia trait in pregnancy was associated with increased rates of anemia, transfusion, and adverse maternal and fetal outcomes. Such adverse outcomes include pre‐eclampsia/eclampsia, cesarean delivery, preterm birth and IUGR. These findings underscore the need for tailored peripartum care strategies in this high‐risk population.

BackgroundAnemia is a global burden, with women and children being most at risk. Moreover, anemia during pregnancy has been reported to be associated with adverse outcomes for both the mother and the offspring. In India, anemia is considered a national health issue and is estimated to have the highest prevalence in the world.ObjectivesTo report on the prevalence of anemia in pregnant women in India, to determine offspring outcomes that have been assessed for an association with maternal anemia in India, and to identify gaps in current knowledge.MethodsFour databases (Scopus, MEDLINE, Embase, and Web of Science) were searched using a systematic search strategy to identify relevant studies conducted in India. The search was limited to studies published between 1990 and 2023 and written in English. The exposure of interest was maternal anemia. The review was reported according to the Preferred Reporting Items for Systematic reviews and Meta‐Analyses extension for Scoping Reviews.ResultsA total of 15 studies were included in this review. The reported prevalence of maternal anemia ranged from 21.26% to 90.46%. A total of 37 offspring outcomes were assessed for an association with maternal anemia, and the most widely reported outcomes related to offspring birthweight.ConclusionMaternal anemia during pregnancy appears to adversely affect the physical and cognitive development of Indian children. However, it remains unclear as to whether such adverse effects persist into adolescence and adulthood. Further research is needed to assess the long‐term effects of maternal anemia to develop suitable health interventions.

The effect of pretransfusion hemoglobin on transfusion burden, thrombosis, and mortality in thalassemia and myelodysplastic syndrome is unclear. We aimed to study the pretransfusion hemoglobin and erythrocyte transfusion burden and investigate the effects of these variables on each other in real-life in thalassemia and myelodysplastic syndrome. Adult patients with thalassemia and myelodysplastic syndrome who received at least one erythrocyte concentrate unit outpatient at Sanliurfa Mehmet Akif Inan Training and Research Hospital during 1 year were included in the study. The data were retrospectively obtained. Ethical approval was obtained for the study. Ninety-two patients were included in the study. In thalassemia major, pretransfusion hemoglobin ≥ 9 g/dL was associated with a lower median annual number of transfused erythrocyte concentrate units (15 vs. 27) and median annual number of transfusion sessions (11 vs. 14) p=0.002, p=0.009, respectively). In myelodysplastic syndrome, a pretransfusion hemoglobin level ≥ 8 g/dL was associated with a lower median annual number of transfused erythrocyte concentrate units (6 vs. 24) (p=0.016). In thalassemia major with an intact spleen, pretransfusion hemoglobin ≥ 8 g/dL was associated with an increased median annual number of transfused erythrocyte concentrate units (32 vs. 27) and median annual number of transfusion sessions (18 vs. 14) (p=0.046, p=0.038, respectively). In conclusion, higher pretransfusion hemoglobin levels were related to a lower transfusion burden in thalassemia major and myelodysplastic syndrome.

Anemia is the most common hematologic abnormality associated with human immunodeficiency virus (HIV)-infected patients and affects 60% to 80% of patients in late-stage disease. It has a considerable impact on the progression of HIV to advanced stages. This study aimed at assessing the burden of anemia in adult HIV-infected patients who are on highly active antiretroviral therapy (HAART) and have follow-up at Hawassa University Comprehensive Specialized Hospital (HUCSH) Antiretroviral therapy (ART) clinic. A hospital-based retrospective study was conducted among HIV-positive adults on HAART at Hawassa University Compressive Specialized Hospital. The systematic sampling method was used to choose a total of 244 study participants. Data on demographic characteristics, related factors of anemia, latest hemoglobin, CD4, and ART regimens were collected using a structured data abstraction format. The data were cleaned and analyzed using SPSS version 21.0 after being manually checked for completeness. Multivariable logistic regression was carried out to detect elements associated with anemia. A P value of <0.05 was used as a cutoff point to announce statistical significance. The records of 244 patients were examined in total. Anemia was present in 29.9% (95% CI 23.8-35.2) among adult HIV patients. Female sex (AOR: 2.576, 95% (CI: 1.295-5.127)), having tuberculosis (TB) (AOR: 4.873, 95% (CI: 1.534-15.484)), taking a zidovudine (ZDV)-containing ART regimen (AOR: 5.216, 95% (CI: 1.239-21.962)), having clinical WHO stage IV and III diseases (AOR: 3.077, 95% CI (1.244-7.612)), having body mass index (BMI) <18.5 kg/m2 (AOR: 2.391, 95% (CI: 1.138-5.023)), and taking cotrimoxazole prophylaxis (AOR: 3.860 95% (CI: 1.097-13.576)) were substantially linked to the development of anemia among adult HIV patients. Conclusion and Recommendation. This study showed that anemia is still a problem among HIV patients on HAART. The burden of anemia was found to be high among patients with advanced WHO clinical stages, having a BMI less than 18.5 kg/m2, TB/HIV coinfection, being on AZT-based ART regimens, and taking cotrimoxazole preventive therapy (CPT). Consequently, it is suggested that early preventative interventions, such as serial hemoglobin follow-up, iron supplementation, and education about dietary consumption, be undertaken targeting the aforementioned groups. In addition, the preferred first-line ART regimen as per the latest national and WHO guidelines is recommended, especially for the above groups.

Background Anemia is a major public health problem worldwide. Adolescent girls are the most vulnerable group of population due to different reasons. The aim of this study was to assess the prevalence of anemia and associated factors among school adolescent girls in rural towns of Bahir Dar City Administration, North West Ethiopia. Methods A cross-sectional study was conducted from March 5 to April 15, 2017, on 443 randomly selected school adolescent girls. Data were collected using pretested structured questionnaire and anthropometric measurements. Blood sample was also collected to assess the hemoglobin (Hgb) value of study participants. SPSS version 20 was used to analyze data. Descriptive statistics were used to describe data. Bivariate and multivariable logistic regression models were used to identify the associated factors with the outcome variable. Crude and adjusted odds ratios with 95% confidence interval (CI) were calculated to identify the variables significantly associated with the outcome variable. Result The prevalence of anemia was 11.1%. Household family size [AOR=3.2, 95%CI (1.29-7.89)], average household monthly income <500 ETB [AOR=10; 95%CI (2.49-41.26)], 501-1000 ETB [AOR=6, 95%CI (2.54-14.33)], history of intestinal parasitic infection [AOR=2.7; 95% CI (1.19-6.21)], duration of menstruation flow [AOR=2.4; 95%CI (1.08- 5.44)], and BMI for age [AOR-3.2; 95% CI (1.43-7.05)] were the predictors of anemia. Conclusion and Recommendation Anemia was a mild public health problem among school adolescent girls in the study area. Household monthly income, family size, intestinal parasite infections, duration of menstruation, and BMI for age are predictors of anemia. Thus, intervention strategies should focus on prevention and early treatment of intestinal parasite, nutritional education, screening, and iron supplementation programs to prevent anemia among school adolescent girls.

Background Thalassemia is a common congenital hemolytic disorder. In severe cases, regular blood transfusion is essentially required. The role of premedications to prevent transfusion reactions is varied among institutions with no standard guideline. Objective To prospectively compare the risk of transfusion reactions in thalassemia patients premedicated with acetaminophen and chlorpheniramine maleate (CPM) versus placebo prior to blood transfusion. Material and Method A randomized, double-blinded, placebo-controlled transfusion reaction study of 147 eligible patients was analyzed. All administered red blood cell (RBC) products were leukoreduced blood products. Patients were monitored and followed for the development of transfusion reactions for 24 hours after RBC transfusion. Results A total of 73 patients randomized to receive active drugs consisting of acetaminophen and CPM were compared to 74 patients receiving placebo. The overall incidences of febrile reaction and urticarial rash were 6.9% and 22% in the patients randomized to receive active drugs comparing with 9.5% and 35.2% in the patients receiving placebo with no significant differences between two groups. However, delayed development of urticarial rash at 4-24 hours after RBC transfusion was significantly higher in female and patients receiving placebo. Conclusion Administration of premedications in thalassemia patients receiving RBC transfusion without a history of transfusion reactions does not decrease the overall risk of transfusion reactions. However, the use of CPM might be beneficial to prevent delayed urticarial rash in those patients especially in females (Thai Clinical Trial Registry (TCTR) study ID: 20140526001).