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Context.--Recently, new technologies, such as nextgeneration sequencing and third-generation sequencing, have been used in carrier screening of thalassemia. However, there is no direct comparison between the 2 methods in carrier screening of thalassemia. Objective.--To compare the clinical performance of third-generation sequencing with next-generation sequencing in carrier screening of thalassemia. Design.--Next-generation sequencing and third-generation sequencing were simultaneously conducted for 1122 individuals in Hainan Province. Results.--Among 1122 genetic results, 1105 (98.48%) were concordant and 17 (1.52%) were discordant between the 2 methods. Among the 17 discordant results, 4 were common thalassemia variants, 9 were rare thalassemia variants, and 4 were variations with unknown pathogenicity. Sanger sequencing and polymerase chain reaction for discordant samples confirmed all the results of thirdgeneration sequencing. Among the 685 individuals with common and rare thalassemia variants detected by third-generation sequencing, 512 (74.74%) were carriers of athalassemia, 110 (16.06%) were carriers of b-thalassemia, and 63 (9.20%) had coinheritance of a-thalassemia and bthalassemia. Three thalassemia variants were reported for the first time in Hainan Province, including --THAI, -α2.4, and ααααanti3.7. Eleven variants with potential pathogenicity were identified in 36 patients with positive hemoglobin test results. Among 52 individuals with negative hemoglobin test results, 17 were identified with thalassemia variants. In total, third-generation sequencing and next-generation sequencing correctly detected 763 and 746 individuals with variants, respectively. Third-generation sequencing yielded a 2.28% (17 of 746) increment compared with next-generation sequencing. Conclusions.--Third-generation sequencing was demonstrated to be a more accurate and reliable approach in carrier screening of thalassemia compared with next-generation sequencing. [ABSTRACT FROM AUTHOR]

Background: Conventional thalassemia screening takes a stepwise approach and has limitations in comprehensively identifying all spectrums of mutations. This study aimed to investigate the performance of third-generation sequencing (TGS) compared to conventional molecular testing. Methods: TGS was applied to validate all known variants detected by conventional testing and to detect missing variants in undiagnosed cases. The study was conducted at Maharaj Nakorn Chiang Mai Hospital between December 2021 and April 2022. Results: In total, 19 cases were included in this study, among which 52.6% (10/19) had known thalassemia variants, while 47.7% (9/19) cases were undiagnosed by conventional methods. All 16 variants previously detected were validated by TGS, and TGS additionally detected 43.8% (7/16) thalassemia variants for 36.8% (7/19) cases. Conclusion: TGS could provide additional genetic diagnoses compared with conventional methods. Further cost-effectiveness studies with a larger sample size are needed to explore the role of TGS in clinical practices. [ABSTRACT FROM AUTHOR]

Objective To compare the diagnostic performance of 10 mathematical formulae for identifying thalassemia trait in blood donors. Methods Compete blood counts were conducted on peripheral blood specimens using the UniCel DxH 800 hematology analyzer. Receiver operating characteristic curves were used to evaluate the diagnostic performance of each mathematical formula. Results In the 66 donors with thalassemia and 288 subjects with no thalassemia analyzed, donors with thalassemia trait had lower values for mean corpuscular volume and mean corpuscular hemoglobin than subjects without thalassemia donors (77 fL vs 86 fL [ P  < .001]; 25 pg vs 28 pg [ P  < .001]). The formula developed by Shine and Lal in 1977 showed the highest area under the curve value, namely, 0.9. At the cutoff value of <1812, this formula had maximum specificity of 82.35% and sensitivity of 89.58%. Conclusions Our data indicate that the Shine and Lal formula has remarkable diagnostic performance in identifying donors with underlying thalassemia trait. [ABSTRACT FROM AUTHOR]

The article focuses on the false positive results of the Hb Bart's immunochromatographic strip test (AT-ICT) for alpha thalassaemia in individuals with delta-beta thalassaemia trait, as confirmed by genetic analysis of the alpha globin gene cluster. Topics include the clinical significance of alpha thalassaemia mutations, the introduction and advantages of the AT-ICT, and the identification of cases with discordant results, highlighting the need for genetic analysis in such instances.

Hemoglobin disorders are among the most common genetic diseases worldwide. Molecular diagnosis is helpful in cases where the diagnosis is uncertain and for genetic counseling. Protein‐based diagnostic techniques are frequently adequate for initial diagnosis. Molecular genetic testing is pursued in some cases, particularly when a definitive diagnosis is not possible and especially for the purpose of assessing genetic risk for couples wanting to have children. The expertise available in the clinical hematology laboratory is essential for the diagnosis of patients with hemoglobin abnormalities. Initial diagnoses are made using protein‐based techniques such as electrophoresis and chromatography. Based on these findings, genetic risk to an individual's offspring can be assessed. In the setting of β‐thalassemia and other β‐globin disorders, coincident α‐thalassemia may be difficult to diagnose, which can have potentially serious consequences. In addition, unusual forms of β‐thalassemia caused by deletions in the β‐globin locus cannot be definitively characterized using standard techniques. Molecular diagnostic testing has an important role in the diagnosis of hemoglobin disorders and is important in the setting of genetic counseling. Molecular testing also has a role in prenatal diagnosis to identify fetuses affected by severe hemoglobinopathies and thalassemias. [ABSTRACT FROM AUTHOR]

Aim: This study aimed to examine the life satisfaction and difficulties experienced by the family members of individuals with thalassemia. Design: This study design is mix‐method research. This research adheres to the COREQ guidelines and checklist. Methods: The research was conducted in the Blood Diseases Polyclinic of a state hospital in a Mediterranean city in Turkey between February 2022 and April 2022. Results: The mean life satisfaction scale score was 11.18 ± 5.13, and a negative correlation was found between the mother's age and life satisfaction score (r = −0.438; p = 0.042, p < 0.05). Qualitative analysis of the experiences of the family members of individuals with thalassemia yielded 10 themes. [ABSTRACT FROM AUTHOR]

Purpose: R2*, a measurement obtained using magnetic resonance imaging (MRI) can be used to estimate liver iron concentration (LIC). 3 T and 1.5 T scanners can be used but conversion of 3 T R2* to LIC is less well validated. In this study the aim was to compare 3 T-R2* LIC and 1.5 T-R2* LIC estimations to assess if they can be used interchangeably. Methods: Thirty participants were scanned at both 1.5 T and 3 T. R2* was measured at both field strengths. 3 T R2* and 1.5 R2* were compared using linear regression and were converted to LIC using different calibration curves. Pearson's rho and Intraclass Correlation Coefficients (ICCs) were used to assess correlation and agreement between 1.5 and 3 T LIC. Bland Altman plots were used to assess bias and limits of agreement. Results: All 1.5 T and 3 T LIC comparisons gave Pearson's rho of 0.99 (p < 0.001). ICC ranged from 0.83 (p = 0.005) to 0.96 (p < 0.001). Biases had magnitude of less than 0.2 mg/g dry weight. Conclusion: Agreement and bias between 3 and 1.5 T-R2* LIC depended on the method used for conversion. There were instances when the agreement was excellent and bias was small, indicating that potentially 3 T-R2* LIC can be used alongside or instead of 1.5 T-R2* LIC but care needs to be taken over the conversion methods selected. Trial registration number: Clinicaltrials.gov NCT03743272, 16 November 2018. [ABSTRACT FROM AUTHOR]

Background: Erythrocyte parameter analysis is the important means for diagnosis and treatment of hematological diseases, which are essential for screening of thalassemia in southern China combined with hemoglobin electrophoresis analysis. But little is known regarding the reference intervals (RIs) in healthy pediatrics in these two areas. Methods: 95% RIs of erythrocyte parameters were calculated from 853 healthy preschoolers, aged from 1 days to <6 years, according to the C28‐A3C guidelines of the Institute of Clinical and Laboratory Standards. To express the magnitude of sex and age variation, standard deviation ratio (SDR) was calculated using ANOVA. Concurrently, we selected 3814 thalassemia carriers as carriers group and drew receiver operating characteristic (ROC) curves to establish the optimal cut‐off values of hemoglobin electrophoresis parameters, which were used as the upper/lower limits of RIs to efficiently screen thalassemia. Results: All parameters except red blood cell (RBC) required age partitioning, confirmed by SDRage above.4. There was no need for sex partitioning on all parameters, confirmed by SDRsex below.4. The optimal cut‐off value of Hemoglobin A2 (Hb A2) in the four subgroups was <7.8% (Hb A), 2.3%–3.2%, 2.5%–3.6% and 2.6%–3.6%, respectively. Conclusion: In this study, the establishment of RIs improved the diagnostic efficiency of hematological disease (especially thalassaemia) for children in Guangxi. It provides reliable hematological references for the identification and diagnosis, treatment monitoring, and health screening of children's clinical diseases. [ABSTRACT FROM AUTHOR]

Extramedullary hematopoiesis is a common complication of ineffective erythropoiesis and bone marrow replacement disorders. Because of its nonspecific presentation and radiological appearance, diagnosing focal intrahepatic extramedullary hematopoiesis is challenging and often misdiagnosed as a hepatic tumor. Herein, we describe the case of a 48-year-old male with thalassemia and AE Bart's disease with secondary hemochromatosis and cirrhosis who developed focal intrahepatic extramedullary hematopoiesis mimicking hepatocellular carcinoma. After hepatic resection, extramedullary hematopoiesis was not observed at any site, including in the remaining liver, at the 4-year follow-up. [ABSTRACT FROM AUTHOR]

* Context.--Underuse of laboratory testing has been previously investigated in preselected populations, such as documented malpractice claims. However, these numbers might not reflect real-life situations. Objective.--To evaluate the underuse and misuse of laboratory follow-up testing in a real-life hospital patient population with microcytic anemia, using laboratory results ordered during routine patient care. Design.--From all patients in whom a microcytic anemia was detected during routine diagnostics in 2018, all available laboratory data were collected and screened for appropriateness of diagnostic workup of iron deficiency and thalassemia. Subgroup analysis was performed for patient groups with mean corpuscular volume values 75 to 79 µm³ (group 1), 65 to 74 µm³ (group 2), and <65 µm³ (group 3). Results.--A total of 2244 patients with microcytic anemia were identified. Follow-up testing for iron deficiency was not performed in 761 cases (34%). For inconclusive ferritin levels due to elevated C-reactive protein results (n = 336), reticulocyte hemoglobin content or soluble transferrin receptor levels were missing in 86 cases (26%). In patients with suspected thalassemia (n = 127), follow-up testing for hemoglobin variants was not performed in 70 cases (55%). Subgroup analysis showed that the frequency of underuse of iron status as well as thalassemia/hemoglobinopathy testing decreased from group 1 to group 3. When considering relevant preexisting anemia diagnoses, laboratory tests were underused in 904 cases (40.3%). Conclusions.--Because 40% (n = 904) of the patients with microcytic anemia were potentially not followed up correctly, laboratory specialists are advised to act by implementing demand management strategies in collaboration with clinicians to overcome underuse of laboratory tests and to improve patient safety. [ABSTRACT FROM AUTHOR]

Background: Although cardiac magnetic resonance (CMR) is the most reliable tool for assessment of CIO in patients with thalassemia, it is not always readily available. Recent studies have explored the potential of GLS as an alternative for diagnosis of CIO. We aimed to investigate the efficacy of global longitudinal strain (GLS) for detection of cardiac iron level (CIO).Methods: We searched SCOPUS, MEDLINE, and Embase to identify the studies which used GLS for assessment of CIO. We searched for individual participant data (IPD) in eligible studies to perform ROC curve analysis. CMR with a T2* cut-off value of 20 ms was considered as the gold standard. A meta-analysis was performed and the risk of bias was assessed using the JBI Checklist.Results: A total of 14 studies with 789 thalassemia patients (310 and 430 with and without CIO respectively and 49 with undetermined condition) were considered eligible for meta-analysis. IPDs of 405 participants were available. GLS was significantly lower in patients with CIO (-17.5 ± 2.7%) compared to those without CIO (-19.9 ± 2.3%; WMD = 1.6%, 95% CI = [0.76-2.4], p = 0.001, I2 = 77.1%) and to normal population (-20.61 ± 2.26%; WMD = 2.2%, 95% CI = [0.91-3.5], p = 0.001, I2 = 83.9%). A GLS < -19.5% could predict CIO with 92.8% sensitivity and 34.63% specificity (AUC = 0.659, 95% CI = [0.6-0.72], p-value < 0.0001). A GLS value < -6% has 100% positive predictive and ≥ -24.5% has 100% negative predictive values for detection of CIO.Conclusions: According to our study, GLS is a strong predictor of CIO and when CMR is not available, it may be a useful screening method for identification of CIO in thalassemia patients. [ABSTRACT FROM AUTHOR]

Thalassemia poses a major public health concern in Bangladesh with a high prevalence of carriers. However, there is a substantial knowledge gap regarding its epidemiology, clinical aspects, and treatment outcomes. Despite its high prevalence, there is a notable lack of awareness regarding thalassemia in the Bangladeshi population. The absence of precisely validated data impedes a comprehensive understanding of this disease.Premarital thalassemia screening is reportedly a successful strategy for countries such as Saudi Arabia and Iran and has also been proposed for Bangladesh. Mandatory screening coupled with genetic counseling is promising for reducing the prevalence of thalassemia by identifying carriers and providing relevant health education. However, sociocultural barriers, challenges, financial constraints, and health risks associated with prenatal diagnosis and abortion could hinder the success of such programs.Positive outcomes from other countries underscore the effectiveness of such programs in reducing thalassemia incidence. The early identification of carriers and genetic counseling can significantly reduce the burden of thalassemia. Additionally, the strain on the healthcare system would be eased, and the quality of life of thalassemia patients would be improved.In conclusion, based on evidence mandatory premarital screening with genetic counseling could be an effective measure to reduce the prevalence of thalassemia in Bangladesh. Leveraging positive attitudes, adopting successful international models, and addressing existing challenges are crucial for the successful implementation of programs that contribute to the overall health and well-being of the country's population., (© 2024. The Author(s).)

Magnetic resonance imaging T2* screening is the gold standard for detecting cardiac iron overload in thalassemia, but its implementation in Indonesia is limited by the high costs. A predicting formula and scoring system based on low-cost investigations is needed. This cross-sectional study was conducted among thalassemia aged 6-18 years at Rumah Sakit Anak dan Bunda RSAB Harapan Kita Indonesia, during October 2017 to April 2019. All subjects were scheduled for clinical examination, laboratory tests, ECGs, echocardiography, tissue Doppler imaging, and MRIT2*. Multivariate logistic regression was used to identify the formula, simplifying to a scoring system, and risk classification for myocardial iron overload using odds ratio (OR) and 95% confidence interval (CI). Significance was set as p<0,05. We recruited 80 children, of those, 8 (10%) were classified as cardiac iron overload based on MRI T2* screening. Multivariate logistic regression showed determinant factors for cardiac iron overload were hemoglobin (95% CI:1.92-369.14), reticulocyte (95% CI:1.14-232.33), mitral deceleration time (DT) (95% CI:1.80-810.62,), and tricuspid regurgitation (TR Vmax) (95% CI:1.87-1942.56) with aOR of 26.65, 14.27, 38.22, and 60.27 respectively. The formula for cardiac iron overload was decided as 9.32 + 3.28 (Hb) + 2.9 (reticulocyte) + 3.64 (DT) + 4.1 (TR Vmax). A scoring system was defined by simplifying the formula of Hb ≤ 8.2 g/L, reticulocyte ≤0.33%, DT ≤ 114.5 cm/s, and TR Vmax ≥ 2.37 m/s were given a score of 1, while others were assigned 0. Total scores of 0 or 1, 2 and 3 or 4 were categorized as low, moderate, and high risk for iron cardiac overload. The cardiac iron overload formula was 9.32 + 3.28 (Hb) + 2.9 (reticulocyte) + 3.64 (DT) + 4.1 (TR Vmax). Variables of Hb ≤ 8.2 g/L, reticulocyte ≤0.33%, DT ≤ 114.5 cm/s, and TR Vmax ≥ 2.37 m/s were given a score of 1, while others were assigned 0. Total scores of 0 or 1, 2, and 3 or 4 were categorized as low, moderate, and high risk for iron cardiac overload., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Rohimi et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Based on CRISPR/Cas12a triggered ordered concatemeric DNA probes, a "on/off" self-powered biosensor is developed to achieve highly sensitive detection of thalassemia gene CD142 through open-circuit potential-assisted visual signal output. The ingeniously constructed glucose oxidase (GOD)-functionalized ordered concatemeric DNA probe structure can significantly amplify signal output, while the coupled CRISPR/Cas12a system is served as a "signal switch" with excellent signal-transducing capabilities. When the ordered concatemeric DNA probe structure is anchored on electrode, the response signal of the sensing system is in the "signal on" mode. While, the presence of the target activates the non-specific cleavage activity of the CRISPR/Cas12a system, causing the sensing system to switch to the "signal off" mode. In the detection system, GOD catalyzes the oxidation of glucose to produce hydrogen peroxide, which further catalyzes the oxidation of 3,3',5,5'-tetramethylbenzidine (TMB) to form a color product, enabling visual signal of the target through naked-eye color contrast. By employing a multifunctional analytical mode combining electrochemical and visual signal outputs, accurate determination of the target is achieved, with linear ranges of 0.0001-100 pM, and detection limits of 48.1 aM (S/N = 3). This work provides a reference method for sensitive detection of thalassemia genes and holds great diagnostic potential in biomedical applications., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Hemoglobin (Hb) disorders are among the most prevalent inherited diseases. Despite a limited number of involved genes, these conditions represent a broad clinical and prognostic spectrum. The menu of laboratory tests is extensive. From widely available modalities, for example, complete blood count to rather sophisticated molecular technologies, the investigation of Hb disorders recapitulates an increasing complexity of laboratory workup in other medical fields. This review highlights a current state of biochemical and molecular investigation of Hb disorders and offers a glimpse on technologies that are yet to be fully embraced in clinical practice., Competing Interests: Disclosure The authors have nothing to disclose., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Adipocyte fatty acid-binding protein (A-FABP; FABP4) plays a significant role in the pathogenesis and progression of metabolically driven low-grade inflammation and organ damage. This study aimed to evaluate the performance of circulating FABP4 as a predictive and diagnostic biomarker for thalassemia-associated cardiometabolic events. This case-control study enrolled 50 adults with β-thalassemia and 30 age-, sex-, and body mass index-matched controls. Participants underwent a comprehensive evaluation, including complete blood count, liver and kidney function tests, serum blood glucose, lipid profile, and ferritin levels, pelviabdominal ultrasound, ECG, and echocardiography after taking a full medical history and conducting a clinical examination. Serum levels of FABP4 were measured using an Enzyme-Linked-Immunosorbent-Assay. The diagnostic performance of FABP4 was assessed using receiver operator characteristic (ROC) curve analysis to determine optimal values for excluding and confirming cardiometabolic metflammation. The thalassemia cohort exhibited a statistically significant higher concentration of FABP4 compared to the control group (p-value < 0.001). Positive correlations were found between FABP4 and ferritin serum levels above 800 or 1000 ug/L, as well as with ALT, TGS, and LDL (p-value < 0.05). Circulating FABP4 was identified as a statistically significant risk factor for thalassemia-associated cardiometabolic comorbidities (OR = 84.00, 95%CI:18.6-378.6, p-value < 0.001). ROC analysis determined that the FABP4 exclusionary cut-off value > 2.30 ng/ml could effectively discriminate between thalassemia-associated adverse metaflammation and controls, while the FABP4 confirmatory cut-off value was > 2.58 ng/ml. In conclusion, circulating FABP4 appears to be a potential risk factor for predicting progression to cardiometabolic events in thalassemia-associated adverse metaflammation. FABP4 holds promise as a diagnostic and prognostic biomarker for disease monitoring and risk stratification. Further validation through large-scale, multicenter, prospective studies is warranted., (© 2024. The Author(s).)

Background: The analysis of haplotypes of variants is important for pharmacogenomics analysis and noninvasive prenatal testing for monogenic diseases. However, there is a lack of robust methods for targeted haplotyping., Methods: We developed digital PCR haplotype sequencing (dHapSeq) for targeted haplotyping of variants, which is a method that compartmentalizes long DNA molecules into droplets. Within one droplet, 2 target regions are PCR amplified from one template molecule, and their amplicons are fused together. The fused products are then sequenced to determine the phase relationship of the single nucleotide polymorphism (SNP) alleles. The entire haplotype of 10s of SNPs can be deduced after the phase relationship of individual SNPs are determined in a pairwise manner. We applied dHapSeq to noninvasive prenatal testing in 4 families at risk for thalassemia and utilized it to detect NUDT15 diplotypes for predicting drug tolerance in pediatric acute lymphoblastic leukemia (72 cases and 506 controls)., Results: For SNPs within 40 kb, phase relation can be determined with 100% accuracy. In 7 trio families, the haplotyping results for 97 SNPs spanning 185 kb determined by dHapSeq were concordant with the results deduced from the genotypes of both parents and the fetus. In 4 thalassemia families, a 19.3-kb Southeast Asian deletion was successfully phased with 97 downstream SNPs, enabling noninvasive determination of fetal inheritance using relative haplotype dosage analysis. In the NUDT15 analysis, the variant status and phase of the variants were successfully determined in all cases and controls., Conclusions: The dHapSeq represents a robust and scalable haplotyping approach with numerous clinical and research applications., (© Association for Diagnostics & Laboratory Medicine 2024.)

Background: Hemoglobin (Hb) is an important protein in red blood cells and a crucial diagnostic indicator of diseases, e.g., diabetes, thalassemia, and anemia. However, there is a rare report on methods for the simultaneous screening of diabetes, anemia, and thalassemia. Isoelectric focusing (IEF) is a common separative tool for the separation and analysis of Hb. However, the current analysis of IEF images is time-consuming and cannot be used for simultaneous screening. Therefore, an artificial intelligence (AI) of IEF image recognition is desirable for accurate, sensitive, and low-cost screening., Results: Herein, we proposed a novel comprehensive method based on microstrip isoelectric focusing (mIEF) for detecting the relative content of Hb species. There was a good coincidence between the quantitation of Hb via a conventional automated hematology analyzer and the one via mIEF with R 2  = 0.9898. Nevertheless, our results showed that the accuracy of disease diagnosis based on the quantification of Hb species alone is as low as 69.33 %, especially for the simultaneous screening of multiple diseases of diabetes, anemia, alpha-thalassemia, and beta-thalassemia. Therefore, we introduced a ResNet1D-based diagnosis model for the improvement of screening accuracy of multiple diseases. The results showed that the proposed model could achieve a high accuracy of more than 90 % and a good sensitivity of more than 96 % for each disease, indicating the overwhelming advantage of the mIEF method combined with deep learning in contrast to the pure mIEF method., Significance: Overall, the presented method of mIEF with deep learning enabled, for the first time, the absolute quantitative detection of Hb, relative quantitation of Hb species, and simultaneous screening of diabetes, anemia, alpha-thalassemia, and beta-thalassemia. The AI-based diagnosis assistant system combined with mIEF, we believe, will help doctors and specialists perform fast and precise disease screening in the future., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Context.—: Recently, new technologies, such as next-generation sequencing and third-generation sequencing, have been used in carrier screening of thalassemia. However, there is no direct comparison between the 2 methods in carrier screening of thalassemia., Objective.—: To compare the clinical performance of third-generation sequencing with next-generation sequencing in carrier screening of thalassemia., Design.—: Next-generation sequencing and third-generation sequencing were simultaneously conducted for 1122 individuals in Hainan Province., Results.—: Among 1122 genetic results, 1105 (98.48%) were concordant and 17 (1.52%) were discordant between the 2 methods. Among the 17 discordant results, 4 were common thalassemia variants, 9 were rare thalassemia variants, and 4 were variations with unknown pathogenicity. Sanger sequencing and polymerase chain reaction for discordant samples confirmed all the results of third-generation sequencing. Among the 685 individuals with common and rare thalassemia variants detected by third-generation sequencing, 512 (74.74%) were carriers of α-thalassemia, 110 (16.06%) were carriers of β-thalassemia, and 63 (9.20%) had coinheritance of α-thalassemia and β-thalassemia. Three thalassemia variants were reported for the first time in Hainan Province, including -THAI, -α2.4, and ααααanti3.7. Eleven variants with potential pathogenicity were identified in 36 patients with positive hemoglobin test results. Among 52 individuals with negative hemoglobin test results, 17 were identified with thalassemia variants. In total, third-generation sequencing and next-generation sequencing correctly detected 763 and 746 individuals with variants, respectively. Third-generation sequencing yielded a 2.28% (17 of 746) increment compared with next-generation sequencing., Conclusions.—: Third-generation sequencing was demonstrated to be a more accurate and reliable approach in carrier screening of thalassemia compared with next-generation sequencing., Competing Interests: Liu, Mao, R. Xu, and Chen are employees of Berry Genomics Corporation. The authors have no other relevant financial interest in the products or companies described in this article., (© 2024 College of American Pathologists.)

Background and objectives: Major ß-thalassemia refers to a severe form of ß-thalassemia in which, patients need blood transfusions from an early age. Iron overload is an important and long-term complication of repeated blood transfusions. The lungs are one of the sites of iron deposition; therefore, it is essential to investigate lung dysfunction due to iron deposition. This study evaluates pulmonary function tests in ß-thalassemia major patients receiving regular blood transfusions and chelation therapy. Methods: In this cross-sectional descriptive study, 120 patients (68 males and 52 females) with β-thalassemia major aged 6 to 41 years who underwent blood transfusion at Bahrami Children's Hospital (Tehran, Iran) in 2021 were enrolled. The patients underwent hematological and pulmonary function tests on the day of transfusion. Association between pulmonary function tests and demographic and laboratory data was investigated. Results: Spirometry indices including forced expiratory volume in the first second (FEV1), forced vital capacity (FVC), and forced expiratory volume to forced vital capacity ratio (FEV1/FVC) were 86.14%±9.9, 87.86%±11.19, and 98.78%±10.97, respectively. In this study, the percentages of FEV1 and FEV1/FVC of patients older than 23 years were significantly lower compared to patients younger than 23 years. Moreover, a significantly lower FEV1/FVC ratio was seen in patients with higher body mass index and a serum ferritin level above 3,325 ng/dl. The most common impairment (19%) was a restrictive pattern. Conclusion: Age is inversely associated with FEV1 and FEV1/FVC ratio. Moreover, higher body mass index and serum ferritin levels are significantly associated with reduced FEV1/FVC ratio. [ABSTRACT FROM AUTHOR]

Introduction: Newborn screening is an important supplement to thalassemia control and prevention. Capillary electrophoresis (CE) technology has several advantages for thalassemia screening but with low sensitivity, especially for thalassemia carriers. This study aims to illustrate the application of an optimized interpretation model in newborn thalassemia screening by capillary hemoglobin electrophoresis. Methods: Two thousand, two hundred fifty‐eight neonates selected from four regions in China were enrolled and were screened for α‐thalassemia and β‐thalassemia by capillary electrophoresis. Results were interpreted based on an optimized model integrated with multiple parameters. Molecular analysis was carried out in synchrony and used as the gold standard for the screening performance assessment. The consistency among different regions and thalassemia genotypes were also investigated. Results: Among the 2258 neonates, 485 were identified to have a likely diagnosis of thalassemia, and 422 α‐thalassemia, 80 β‐thalassemia, and 21 α/β‐thalassemia cases were confirmed by molecular analysis, including 277 α‐thalassemia silent carriers, 135 α‐thalassemia trait carriers, 10 Hemoglobin H disease, and 80 β‐thalassemia trait carriers. The screening sensitivity, specificity, positive, and negative predictive value for α‐thalassemia and β‐thalassemia were 84.83%, 99.14%, 95.98%, 96.41%, and 88.75%, 98.73%, 76.34%, and 99.48%, respectively. The optimized interpretation model showed higher performance for thalassemia carriers, though some neonates with silent α‐thalassemia genotypes (‐α3.7/αα, ‐α4.2/αα, and αWSα/αα) and β‐28/βN genotype were still missed. The screening performance among different regions was comparable. Conclusions: Capillary hemoglobin electrophoresis with the optimized interpretation model shows reliable performance for newborn thalassemia screening. It is applicable to large‐scale population screening. [ABSTRACT FROM AUTHOR]

Background It is evident that high cell turnover rate is present in patients suffering from β-thalassemia. This is mainly the result of not only chronic hemolysis but also ineffective erythropoiesis. It is thus expected that hyperuricemia will occur. Aim Our study was conducted to study uric acid excretion in β-thalassemia major patients and to determine its relationship to tubular dysfunction in those patients. Patients and methods This case-control study was performed on 60 patients with β-thalassemia major and 15 children who were healthy and well, playing the role of the control group. Thorough history taking, review of medical records, and complete physical examination were done for all patients. Evaluation of uric acid excretion, glomerular and tubular renal functions were performed and compared between patients and the control group. Results Hyperuricemia was found in 48.8% of patients; however, none of the patients had evidence of gouty arthritis or nephrolithiasis. Serum uric acid (SUA) levels in patients who had positive correlation with serum creatinine, urine P/Cr ratio and urine uric acid/glomerular filtration rate (UUA/GFR), negative correlation with eGFR and no correlation with urine calcium/creatinine ((UCa/UCr) ratio, blood urea nitrogen (BUN), urine β2 MG, and urinary uric acid/creatinine (UUa/UCr) ratio were assessed. The mean SUA level, BUN, serum creatinine, and levels of eGFR were significantly higher in β-thalassemia patients in comparison to the control group. Urinary P/Cr ratio, urine uric acid/glomerular filtration rate (UUA/GFR) ratio, β-2 microglobulin levels, (UCa/UCr, and UUa/UCr were also higher in β-thalassemia patients in comparison to the control group. The present study has a mean age of 8.62 years for the cases studied, and investigations in patients revealed the following results: mean SUA 5.17 mg/dl, mean BUN 16.58 mg/dl, mean serum creatinine 0.49 mg/dl, mean urine P/Cr ratio 1.40, mean eGFR 141.42 ml/min/1.73 m², mean UUA/GFR 0.55, mean urine β2 MG 0.18 μg/ml, mean (UCa/UCr 0.44, UUa/UCr 1.46, and these results were statistically significantly higher in patients compared with controls. Conclusion Renal dysfunction and hyperuricemia are prevalent among patients with β-thalassemia major, mostly related to hyperfiltration and tubular dysfunction. Early markers of tubular dysfunction (urine β2 MG, (UCa/UCr, UUa/UCr) and glomerular dysfunction (urine P/Cr ratio and urinary uric acid/GFR ratio) should be followed up regularly in β-thalassemia major patients. [ABSTRACT FROM AUTHOR]

Background In Egypt, it has been established that the most frequently inherited disorder of hemoglobin is β-thalassemia. Management of the severe forms of this disorder consists chiefly of red cell transfusion. The concerned patients receive these transfusions on a regular basis. Therefore, the formation of antired cell alloantibodies and autoantibodies was inevitable. This dilemma is addressed in this study that aims to determine the prevalence of red cell alloimmunization among transfusion-dependent ß-thalassemia children that receive frequent care in the Hematology Clinic of Alexandria University Children's Hospital. Patients and methods This study screened 100 transfusion-dependent patients in total, all of them were 3-16 years old. Transfusion and clinical records of the latter were reviewed to assess the diagnosis of β-thalassemia, the age of the first presentation, the age at which transfusion therapy was started, transfusion interval, and the number of red cell units given. Alloantibody detection was then performed. Results In the present study, 11 (11%) out of the total 100 studied patients were alloimmunized. The total number of alloantibodies identified in these patients was 25. Two patients (18%) had only one alloantibody, six patients (54.5%) had two alloantibodies, one patient (9%) had three alloantibodies, and two patients (18%) had more than three alloantibodies. The most prevalent antibodies belonged to Kell and Rh blood-group systems (seven out of 25 each). Conclusions When it comes to thalassemia patients dependent on blood transfusion, red blood cell alloimmunization is a difficult complication. Kell and RH blood-group-system antibodies are the predominant antibodies. Formation of alloantibodies depends mainly on the nature of red cell units received and donor and recipient factors. These can explain the difference in alloimmunization rates in different reports. Avoidance of alloimmunization would decrease the cost of treatment on the long run and improve the patient quality of life. [ABSTRACT FROM AUTHOR]

Background: Decreasing signal intensity of the spleen assessed by T2* MRI is a frequent finding in patients with beta-thalassemia due to iron deposition within the reticuloendothelial cells in this organ. This parameter can also be applied to determine the candidates for blood cell transfusion. However, the association between splenic siderosis and iron overload in other vital organs such as heart and liver remains unclear. The present study aimed to assess the correlation between iron deposition in splenic, hepatic and myocardial tissues by T2* relaxometry technique. Methods: This cross-sectional study included 39 consecutive patients with a definitive diagnosis of beta-thalassemia major who underwent spleen, liver and heart MRI examinations for iron deposition and cardiac function. Results: No significant correlation was found between the heart and splenic T2* relaxation time (R=0.206, P=0.357). We revealed a strong correlation between the splenic T2* relaxation time and hepatic calculated T2*s (R=0.515, P=0.014). The liver T2* values can be predicted from the splenic T2*s by a new linear equation. According to the ROC curve analysis, the splenic T2* could significantly, but moderately predict moderate to severe from mild liver iron excess (AUC=0.667). Conclusion: Our study demonstrated a significant linear correlation between the splenic and hepatic T2* relaxation time, probably indicative of the same iron deposition mechanism, and made us available to write a linear model that would predict the deposited iron density in the spleen with the use of the magnetic resonance T2* values. [ABSTRACT FROM AUTHOR]

Thalassemia is one of the most common and damaging monogenic diseases in the world. It is caused by pathogenic variants of α- and/or β-globin genes, which disrupt the balance of these two protein chains and leads to α-thalassemia or β-thalassemia, respectively. Patients with α-thalassemia or β-thalassemia could exhibit a severe phenotype, with no simple and effective treatment. A three-tiered strategy of carrier screening, prenatal diagnosis and newborn screening has been established in China for the prevention and control of thalassemia, of which the first two parts have been studied thoroughly. The implementation of neonatal thalassemia screening is lagging, and the effectiveness of various screening programs has not yet been demonstrated. In this study, hemoglobin capillary electrophoresis (CE), hotspot testing method, and third-generation sequencing (TGS) were used in the variant detection of 2000 newborn samples, to assess the efficacy of these methods in neonatal thalassemia screening. Compared with CE (249, 12.45 %) and hotspot analysis (424, 21.2 %), CATSA detected the largest number of thalassemia variants (535, 26.75 %), which included 24 hotspot variants, increased copy number of α-globin gene, rare pathogenic variants, and three unreported potentially disease-causing variants. More importantly, CATSA directly determined the cis-trans relationship of variants in three newborns, which greatly shortens the clinical diagnosis time of thalassemia. CATSA showed a great advantage over other genetic tests and could become the most powerful technical support for the three-tiered prevention and control strategy of thalassemia., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

This comprehensive guideline, developed by a representative group of UK-based medical experts specialising in haemoglobinopathies, addresses the management of conception and pregnancy in patients with thalassaemia. A systematic search of PubMed and EMBASE using specific keywords, formed the basis of the literature review. Key terms included "thalassaemia," "pregnancy," "Cooley's anaemia," "Mediterranean anaemia," and others, covering aspects such as fertility, iron burden and ultrasonography. The guideline underwent rigorous review by prominent organisations, including the Endocrine Society, the Royal College of Obstetricians and Gynaecologists (RCOG), the United Kingdom Thalassaemia Society and the British Society of Haematology (BSH) guideline writing group. Additional feedback was solicited from a sounding board of UK haematologists, ensuring a thorough and collaborative approach. The objective of the guideline is to equip healthcare professionals with precise recommendations for managing conception and pregnancy in patients with thalassaemia., (© 2024 British Society for Haematology and John Wiley & Sons Ltd.)

This paper aims to propose an approach leveraging Artificial Intelligence (AI) to diagnose thalassemia through medical imaging. The idea is to employ a U-net neural network architecture for precise erythrocyte morphology detection and classification in thalassemia diagnosis. This accomplishment was realized by developing and assessing a supervised semantic segmentation model of blood smear images, coupled with the deployment of various data engineering techniques. This methodology enables new applications in tailored medical interventions and contributes to the evolution of AI within precision healthcare, establishing new benchmarks in personalized treatment planning and disease management.

Background: Mild to moderate thalassemia trait (TT) and iron deficiency anemia (IDA) are the most common conditions of microcytic hypochromic anemia (MHA) and they exhibit highly similar clinical and laboratory features. It is sometimes difficult to make a differential diagnosis between TT and IDA in clinical practice. Therefore, a simple, effective, and reliable index is needed to discriminate between TT and IDA., Methods: Data of 598 patients (320 for TT and 278 for IDA) were enrolled and randomly assigned to training set (278 of 598, 70%) and validation set (320 of 598, 30%). Stepwise discriminant analysis was used to define the best diagnostic formula for the discrimination between TT and IDA in training set. The accuracy and diagnostic performance of formula was tested and verified by receiver operating characteristic (ROC) analysis in validation set and its diagnostic performance was compared with other published indices., Results: A novel formula, Thalassemia and IDA Discrimination Index (TIDI) = -13.932 + 0.434 × RBC + 0.033 × Hb + 0.025 ×MCHC + 53.593 × RET%, was developed to discriminate TT from IDA. TIDI showed a high discrimination performance in ROC analysis, with the Area Under the Curve (AUC) = 0.936, Youden' s index = 78.7%, sensitivity = 89.5%, specificity = 89.2%, respectively. Furthermore, the formula index also obtained a good classification performance in distinguishing 5 common genotypes of TT from IDA (AUC from 0.854-0.987)., Conclusion: The new, simple algorithm can be used as an effective and robust tool for the differential diagnosis of mild to moderate TT and IDA in Guangxi region, China., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Non-anemic thalassemia trait (TT) accounted for a high proportion of TT cases in South China., Objective: To use artificial intelligence (AI) analysis of erythrocyte morphology and machine learning (ML) to identify TT gene carriers in a non-anemic population., Methods: Digital morphological data from 76 TT gene carriers and 97 controls were collected. The AI technology-based Mindray MC-100i was used to quantitatively analyze the percentage of abnormal erythrocytes. Further, ML was used to construct a prediction model., Results: Non-anemic TT carriers accounted for over 60% of the TT cases. Random Forest was selected as the prediction model and named TT@Normal. The TT@Normal algorithm showed outstanding performance in the training, validation, and external validation sets and could efficiently identify TT carriers in the non-anemic population. The top three weights in the TT@Normal model were the target cells, microcytes, and teardrop cells. Elevated percentages of abnormal erythrocytes should raise a strong suspicion of being a TT gene carrier. TT@Normal could be promoted and used as a visualization and sharing tool. It is accessible through a URL link and can be used by medical staff online to predict the possibility of TT gene carriage in a non-anemic population., Conclusions: The ML-based model TT@Normal could efficiently identify TT carriers in non-anemic people. Elevated percentages of target cells, microcytes, and teardrop cells should raise a strong suspicion of being a TT gene carrier., (© 2023 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Introduction: Thalassaemia has been prevalent with high morbidity and mortality rates since 1925. Although there is a lack of systematic review on the costs of prevention that has yielded reductions in thalassaemia prevalence, this review will show a widespread presence of complex but effective strategies in reducing national thalassaemia prevalence., Materials and Methods: A systematic search was conducted using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA 2020). Designated keywords were combined with search functions and Boolean operators in databases like Scopus, Web of Science and several other search databases., Results: The search identifed 5425 potential articles. Most countries reported a decline in thalassaemia prevalence after implementing intervention programmes for several decades. The screening methods, however, varies, and the speed of reductions depends on the type of screening approach that involves blood screening of adolescence and antenatal mothers and, in some countries, includes termination of pregnancy. In addition, the cost of these initiatives varies as it was challenging to find a common denominator. However, the endpoint concedes that the cost of screening, although substantial, would be offset by the cost of reduction of cases. In some countries, cost-effectiveness analyses have been reported to support the initiatives of thalassaemia screening and prevention in the long run., Conclusion: The results showed significant variations in success rates with a significant reduction in the prevalence of Thalassaemia. Most successful are countries with comprehensive and aggressive prevention and control programmes that engaged with lab screening, counselling, and termination of pregnancy as a package.

Thalassemia is most widely distributed single gene autosome recessive genetic disease in the world, whose clinical manifestation was changed from asymptomatic anemia to severe anemia requiring continous blood transfusion to maintain life, thus resulting in a serious economic burden to society and families. Therefore, it is necessary to carry out the corresponding prentatal screening and diagnosis. Most of the conventional detection methods can only detect the common thalassemia genotype, it can easy to cause misdiagnosis or missed diagnosis for those rate genetic variantions. The third-generation sequecing (TGS) has been applied to the detection of thalassemia genes, which is more accurate, reliable and superior to the converntional detection methods. This article reviews the latest research progress of the TGS technology in genetic testing of thalassemia.

There is no regulatory mechanism for the removal of iron that accumulates in the body. Thalassemia patients are most affected by iron overload. The method often used in the treatment of these patients is iron chelation therapy, which involves removing excess iron from the bloodstream, but it is insufficient. Nutritional supplements and herbal remedies are complementary tools that may help improve the health of an individual with iron load. Here, we tried to develop a method that affecting intestinal absorption in an animal model with clinoptilolite feeding to reduce the iron load in the circulation. 32 rats were divided into 4 groups as control, Cli, Iron, Cli+Iron. Iron and Cli+Iron groups received iron at a dose of 250 mg/kg/day for 10 days, and Cli and Cli+Iron groups were fed a diet with 50% clinoptilolite for one month. Histological preparation and Fe2+, Cu2+, Zn2+ measurements were done in all tissues. Consequently, clinoptilolite significantly lowered the iron level in the stomach. On the contrary, iron absorption was increased in the small intestine, but iron transportation to the blood was decreased by clinoptilolite. The iron levels of clinoptilolite groups (Cli and Cli+Iron) were reduced in the tissues of heart, lung, liver, kidney, and spleen because of the different level of iron necessities of each tissue compared to the group with iron overload. The clinoptilolite could preserve organs against iron toxicity by enhancing the absorption of iron in the small intestine but lowering the iron level in blood. Even though there was no detailed information regarding the mechanism of reduction iron overload by the clinoptilolite, serum and chyme could help to make some helpful inferences to elucidate the mechanism of iron chelation. [ABSTRACT FROM AUTHOR]

The article presents Characterization and identification of Prachinburi β0 thalassemia, and the novel-60 kb deletion in beta globin gene related to high levels of Hb F in heterozygous state. Topics discussed include β-Thalassemia is one of the most common genetic disorders in tropical and subtropical countries; and this defect is represented by decreasing (β+) or absent (β0) β-globin chain production from the β-globin gene on the chromosome.

Introduction: Thalassaemia trait (TT) is potential to be missed clinically, especially normocytic thalassaemia. We aimed to establish discriminant functions (DFs) and an algorithm for detecting microcytic or normocytic TT in epidemiological screening. Methods: The receiver operating characteristics (ROC) curve analysis was used to determine the diagnostic performance of the proposed formulas in differentiating TT and nonthalassaemia (non‐TT). DFs combined the two blood count parameters with the highest performance, based on the area under the curve (AUC) value, into mathematical formulas, using logistic regression. The diagnostic efficacy of DFs was subsequently evaluated in 761 participants, and reliability (including adjusted agreement [AA] and Kappa values) and validity (including sensitivity, specificity, likelihood ratio and Youden's Index) were calculated. Results: Among microcytic participants, the proposed DFs showed good diagnostic performance (in females: AUC = 0.892 [DF1 = 0.015 × RDW‐CV/RBC − 0.096 × RDW‐SD/RBC + 1.29], in males: AUC = 0.861 [DF2=−0.025 × RDW‐SD/RBC − 0.035 × MCV/RBC + 1.415]). Youden's Index, AA and Kappa values for microcytic TT detection were 0.72, 0.86, and 0.72 and 0.63, 0.81 and 0.63 for females and males, respectively. In normocytic participants with RDW‐CV/RBC ≤ 3.54, DF3=−0.38 × MCH−0.02 × MCHC+17.37 achieved AUC = 0.857 in females, whereas DF4 = 0.007 × MCV−0.113 × MCH+2.829 achieved AUC = 0.969 in males. The Youden's Index, AA and Kappa values for the proposed DFs for thalassaemia detection were 0.69, 0.84 and 0.67 in females, 0.76, 0.91 and 0.71 in males, respectively. Conclusion: The proposed DFs performed well in the detection of TT among participants with microcytic and normocytic parameters and could be utilized in epidemiological study for TT. [ABSTRACT FROM AUTHOR]

Introduction: Red blood cells (RBCs) in patients with thalassemia and iron deficiency anemia (IDA) exhibit different patterns of morphological changes. However, manual quantitative analysis of the morphological changes in the RBCs is time‐consuming and subjective, limiting its use in differential diagnosis. The aim of this study was to evaluate the CellaVision Advanced RBC software as a prescreening tool for differential diagnosis of thalassemia and IDA. Methods: The study cohort consisted of 54 thalassemia and 46 IDA cases in the training group and 36 thalassemia and 31 IDA patients in the validation group. The CellaVision DM96 Advanced RBC software was used to analyze the RBC morphology. Results and Conclusion: Specific patterns of quantitative changes in RBC shapes were found in thalassemia and IDA patients. As a single parameter, target cell was the best morphological cell type to distinguish thalassemia from IDA, with an area under the curve (AUC) of 0.79, followed by hypochromatic cells with an AUC of 0.70. Combination of target and hypochromatic cells expressed as a ratio of the percentage of target cells to percentage of hypochromatic cells (T/H ratio) presented better differential diagnostic ability with an AUC of 0.88. A cutoff value of 1.755 for T/H ratio showed a sensitivity and specificity of 80.43% and 81.48% in the training group and 88.89% and 80.65% in the validation group, respectively. Assessment of the T/H ratio using the CellaVision Advanced RBC software represents a relatively simple and economical screening procedure for diagnostic testing of thalassemia and IDA. [ABSTRACT FROM AUTHOR]

Alpha thalassemia (α-thalassemia) is an autosomal recessive disorder due to the reduction or absence of α globin chain production. Laboratory diagnosis of α-thalassemia requires molecular analysis for the confirmatory diagnosis. A screening test, comprising complete blood count, blood smear and hemoglobin quantification by high performance liquid chromatography and capillary electrophoresis, may not possibly detect all the thalassemia diseases. This review focused on the molecular techniques used to detect α-thalassemia, and the advantages and disadvantages of each technique were highlighted. Multiplex gap-polymerase chain reaction, single-tube multiplex polymerase chain reaction, multiplex ligation-dependent probe amplification, and loop-mediated isothermal amplification were used to detect common deletion of α-thalassemia. Furthermore, the reverse dot blot analysis and a single tube multiplex polymerase chain reaction could detect non-deletion mutation of the α-globin gene. Sanger sequencing is widely used to detect non-deletion mutations of α-thalassemia. Recently, next-generation sequencing was introduced in the diagnosis of both deletion and point mutations of α-thalassemia. Despite the advantages and disadvantages of different techniques, the routine method employed in the laboratory should be based on the facility, expertise, available equipment, and economic conditions. [ABSTRACT FROM AUTHOR]

When caring for pregnant women at risk for fetal thalassemia, genetic counseling is typically employed to ensure the quality of care and to fulfil individual needs. This qualitative descriptive study aimed to understand women's experiences and further refine their woman-centered care. Through a purposive sampling technique, 20 Thai women in a northeastern province participated in this study, having had undergone prenatal screening and diagnostic tests, and terminated the pregnancy or given birth. Most informants were interviewed in-depth two or three times. Data were analyzed using thematic analysis. Six caregiving themes emerged from their experiences: Theme 1, Amending ambiguity containing sub-themes of Assessing ambiguity in thalassemia, and Making clear the unknown; and Theme 2, Respecting individual difference which described the sub-themes of Assessing and accepting different values; Mother's heartbreak versus a baby living normally, Safeguarding a baby from suffering versus giving life to a baby, and Facilitating shared decisions, without using directives and coercion. Theme 3 was Prioritizing an unborn baby's well-being including the subthemes of Nourishing an unborn baby, and Reassuring an unborn baby's safety, while Theme 4 was Caring beyond courteousness that described the sub-themes of Assistance to regain emotional balance; Enhancing mental strength, and Facilitating religious and spiritual coping. Theme 5, Care given extensively to family and community involved Intervening when 'My family hurt,' and 'I hurt my family,' and Alleviating concerns over community attitude. The last theme, Reducing negative experiences with service delivery, involved sub-themes of Reducing a sense of prolonged waiting and being rushed, and Reducing a sense of limited expertise and technology. In conclusion, regarding a woman-centered approach for these women, nurses should respond to their unique psychosocial, cultural, ethical, religious, and spiritual needs, respect the woman's values, dignity, and decisions, as well as extend the care to the fetus, family, and community. [ABSTRACT FROM AUTHOR]

β-Thalassemia/HbE disease has a wide spectrum of clinical phenotypes ranging from asymptomatic to dependent on regular blood transfusions. Ability to predict disease severity is helpful for clinical management and treatment decision making. A thalassemia severity score has been developed from Mediterranean β-thalassemia patients. However, different ethnic groups may have different allele frequency and linkage disequilibrium structures. Here, Thai β0-thalassemia/HbE disease genome-wild association studies (GWAS) data of 487 patients were analyzed by SNP interaction prioritization algorithm, interacting Loci (iLoci), to find predictive SNPs for disease severity. Three SNPs from two SNP interaction pairs associated with disease severity were identifies. The three-SNP disease severity risk score composed of rs766432 in BCL11A, rs9399137 in HBS1L-MYB and rs72872548 in HBE1 showed more than 85% specificity and 75% accuracy. The three-SNP predictive score was then validated in two independent cohorts of Thai and Malaysian β0-thalassemia/HbE patients with comparable specificity and accuracy. The SNP risk score could be used for prediction of clinical severity for Southeast Asia β0-thalassemia/HbE population. [ABSTRACT FROM AUTHOR]

Background and Objectives: The C Willis or Cw antigen is a low-incidence antigen of Rh system. The antibody against the Cw antigen (anti-Cw) is an IgG antibody which may occur naturally or may be immune in nature. The identification of Cw antibody is important since it has the potential to cause hemolytic disease of the newborn as well as hemolytic transfusion reaction. This study was conducted with the aim of determining the prevalence of Cw antibody in multitransfused thalassemic patients enrolled in a Regional Blood Transfusion Center (RBTC) of North India. Methods: A retrospective descriptive observational study was conducted at the Department of Immunohematology and Blood Transfusion, LHMC and Associated Hospitals. All transfusion-dependent thalassemic (TDT) patients and non-TDT (NTDT) patients enrolled in the RBTC of the hospital till December 2018 were included in the study. Antibody screening was performed in all recipients before each transfusion. The prevalence of anti-Cw was estimated. Results: A total of 567 thalassemic patients (including TDT and NTDT) were registered in RBTC, LHMC till December 2018. On pretransfusion antibody screening and identification, 3 out of 567 thalassemic patients were found to have alloimmunization against Cw antigen. The prevalence of anti-Cw in multitransfused thalassemics was 0.53%. Conclusion: The prevalence of anti-Cw is variable in different populations and it is not a very commonly reported antibody in patients with thalassemia. One should be aware of the approach to transfusion in thalassemic patients who develop Cw alloimmunization. [ABSTRACT FROM AUTHOR]

To explore a noninvasive method for diagnosis of SEA-thalassemia and to investigate whether the regional factors affect the accuracy of this method. The method involved using a public database and bioinformatics software to construct parental haplotypes for proband and predicting fetal genotypes using relative haplotype dosage. We screened and downloaded sequencing data of couples who were both SEA-thalassemia carriers from the China National Genebank public data platform, and matched the sequencing data format with that of the reference panel using Ubuntu system tools. We then used Beagle software to construct parental haplotypes, predicted fetal haplotypes by relative haplotype dosage. Finally, we used Hidden Markov Model and Viterbi algorithm to determine fetal pathogenic haplotypes. All noninvasive fetal genotype diagnosis results were compared with gold standard gap-PCR electrophoresis results. Our method was successful in diagnosing 13 families with SEA-thalassemia carriers. The best diagnostic results were obtained when Southern Chinese Han was used as the reference panel, and 10 families showed full agreement between our noninvasive diagnostic results and the gap-PCR electrophoresis results. The accuracy of our method was higher when using a Chinese Han as the reference panel for haplotype construction in the Southern Chinese Han region as opposed to Beijing Chinese region. The combined use of public databases and relative haplotype dosage for diagnosing SEA-thalassemia is a feasible approach. Our method produces the best noninvasive diagnostic results when the test samples and population reference panel are closely matched in both ethnicity and geography. When constructing parental haplotypes with our method, it is important to consider the effect of region in addition to population background alone.

Context.—: Thalassemia is the most widely distributed monogenic autosomal recessive disorder in the world. Accurate genetic analysis of thalassemia is crucial for thalassemia prevention., Objective.—: To compare the clinical utility of a third-generation sequencing-based approach termed comprehensive analysis of thalassemia alleles with routine polymerase chain reaction (PCR) in genetic analysis of thalassemia and explore the molecular spectrum of thalassemia in Hunan Province., Design.—: Subjects in Hunan Province were recruited, and hematologic testing was performed. Five hundred four subjects positive on hemoglobin testing were then used as the cohort, and third-generation sequencing and routine PCR were used for genetic analysis., Results.—: Of the 504 subjects, 462 (91.67%) had the same results, whereas 42 (8.33%) exhibited discordant results between the 2 methods. Sanger sequencing and PCR testing confirmed the results of third-generation sequencing. In total, third-generation sequencing correctly detected 247 subjects with variants, whereas PCR identified 205, which showed an increase in detection of 20.49%. Moreover, α triplications were identified in 1.98% (10 of 504) hemoglobin testing-positive subjects in Hunan Province. Seven hemoglobin variants with potential pathogenicity were detected in 9 hemoglobin testing-positive subjects., Conclusions.—: Third-generation sequencing is a more comprehensive, reliable, and efficient approach for genetic analysis of thalassemia than PCR, and allowed for a characterization of the thalassemia spectrum in Hunan Province., (© 2024 College of American Pathologists.)

Thalassemia trait is an autosomal recessive genetic disease, which is a hemolytic anemia caused by disturbance of erythrocyte hemoglobin production caused by gene mutation or deletion. Iron deficiency anemia is caused by a lack of iron in the body due to an imbalance between the demand and supply of iron. The laboratory manifestations of both are microcytic hypochromic anemia, but the treatment schemes are completely different, and it is difficult to distinguish them from the results of blood count. Erythrocyte parameters can be used to establish a formula or model to differentiate them, which can achieve the purpose of early screening, early diagnosis and early treatment,preventing the occurrence of severe anemia and providing a scientific basis for the thalassemia and iron deficiency anemia prevention. This article will review the research progress of using erythrocyte parameters to distinguish thalassemia trait with iron deficiency anemia.

The life-threatening genetic blood disorder, thalassaemia, which causes decreased haemoglobin production, is preventable. Sociocultural determinants and the level of public health awareness must be used to adopt control measures of prevention. Identifying information gaps and educating the community about screening should be a priority, especially in areas with high disease burdens. A relevant health education technique, with which the audience can identify, can effectively bring understanding necessary effectively to sensitise the community. We propose the 'Bag and Ball' method, which includes role-play for health education specifically concerning inherited genetic disorders., Competing Interests: Declaration of conflicting interestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background Currently, more than 45 mathematical formulas based on simple red blood cell (RBC) parameters have been proposed for differentiating between iron deficiency and thalassemia in microcytic anemia, of which 20 are relatively new and have not been thoroughly independently verified. The study goal was to verify these 20 new formulas and to identify which RBC parameters have a decisive impact on the performance of those formulas. Methods A database containing laboratory and diagnostic data from 2788 subject individuals with microcytic anemia was used for assessing performance by receiver operating characteristic (ROC) analysis. Results The new Index26 had excellent performance, equivalent to the Green and King, Jayabose, and Janel formulas previously identified in the literature. The discriminant power of nearly all newer formulas was lower in our study than that claimed by the original authors. We discovered that a well-performing formula requires mean cell volume (MCV), RBC distribution width (RDW), and RBC measurements, whereas hemoglobin measurements appeared not to be essential. Conclusions Only the new Index26 performed at a level comparable to the very strongest established formulas. All other new formulas had lower performance than was claimed in the original publications, underscoring that independent verification of new formulas is indispensable. [ABSTRACT FROM AUTHOR]