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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]

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]

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]

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: The current investigation aims to analyze the occurrence of thalassemia in patients who participated in hemoglobin A1c (HbA1c) testing in clinical laboratory showing high hemoglobin F (HbF) level (≥ 1.5%) or abnormal Hb peak and predict the main influence factors by using different statistical models., Methods: The current investigation is a single-center retrospective cohort study. HbA1c concentration was detected by using TOSOH HLC-723G8 glycated hemoglobin analyzer. SNaPshot SNP (Single Nucleotide Polymorphism) typing and AccuCopy technology were employed to detect mutations in thalassemia-related pathogenic genes., Results: A total of 126 patients endured high HbF levels or abnormal Hb peak during HbA1c detection, and 66.7% of subjects (n = 84) showed thalassemia mutations. Three heterozygosity mutations, including c.52A>T (p.K18*), c.-78A>G, and c.126&#95;129delCTTT(p.F42Lfs*19) present in HBB gene, were also identified. -- SEA /αα mutation demonstrated the youngest ages (p < 0.001). 17 M (p < 0.001) and 41/42 M (p < 0.01) mutations with β-thalassemia showed higher HbF levels compared with patients without thalassemia mutations. Except for -α 3.7 , mutations in thalassemia showed lower levels of mean corpuscular hemoglobin (MCH) and mean corpuscular volume (MCV) compared with patients without thalassemia mutations. Patients with thalassemia mutations showed younger age (p < 0.001), lower Hb (p < 0.001), MCV and MCH levels (p < 0.001), higher red blood cell (RBC) count (p < 0.001), and platelet distribution width (PDW) level (p = 0.007) than patients without thalassemia mutations. Three statistical models indicate MCV is the most valuable independent factor for predicting thalassemia and ROC (receiver operating characteristic) curves analysis of AUC (Area Under the Curve) of 0.855 (95% CI [0.787-0.923], p < 0.001) with MCV., Conclusion: High HbF level (≥ 1.5%) or abnormal Hb peak present in HbA1c testing indicated high incident rate of thalassemia. MCV is the most valuable independent predicting factor for subjects having thalassemia., (© 2024 The Author(s). Journal of Clinical Laboratory Analysis published by Wiley Periodicals LLC.)

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.)

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]

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]

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: 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]

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]

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: 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.)

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.)

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]

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]

Background: In China, conventional genetic testing methods can only detect common thalassemia variants. Accurate detection of rare thalassemia is crucial for clinical diagnosis, especially for children that need long-term blood transfusion. This study aims to explore the application value of third-generation sequencing (TGS) in the diagnosis of rare thalassemia in children with anemia., Methods: We enrolled 20 children with anemia, excluding from iron deficiency anemia (IDA). TGS was employed to identify both known and novel thalassemia genotypes, while sanger sequencing was used to confirm the novel mutation detected., Results: Among the 20 samples, we identified 5 cases of rare thalassemia. These included β -4.9 (hg38,Chr11:5226187-5231089) at HBB gene, α -91 ( HBA2 :c.*91delT), α CD30 ( HBA2 :c.91-93delGAG), Chinese G γ + ( A γδβ) 0 (NG&#95;000007.3: g .48795-127698 del 78904) and delta - 77(T > C) ( HBD :c.-127T>C). Notably, the - SEA /α -91 α genotype associated with severe non-deletional hemoglobin H disease (HbH disease) has not been previously reported. Patients with genotypes β 654 /β -4.9 and - SEA /α -91 α necessitate long-term blood transfusions, and those with the - SEA /α CD30 α, Chinese G γ + ( A γδβ) 0 and delta thalassemia demonstrate mild anemia., Conclusions: TGS demonstrates promising potential as a diagnostic tool for suspected cases of rare thalassemia in children, especially those suspected to have transfusion-dependent thalassemia (TDT).

Background In thalassemia patients, reduced zinc absorption results from increased serum iron due to repeated blood transfusions, increased iron absorption due to ineffective erythropoiesis, and competitive inhibition between iron and zinc in binding to transferrin, a means of transporting both types of minerals in the blood. Few studies have been done to examine zinc levels in thalassemia patients and its relationship with ferritin. Objective To compare serum zinc in thalassemia patients and healthy controls and to assess for a possible correlation between serum ferritin and zinc in thalassemia patients. Methods This cross-sectional study in 68 subjects was done from October 2016 to August 2017. Serum ferritin measured by chemiluminescence immunoassay and serum zinc by inductively coupled plasma mass spectrometry (ICP-MS). Wilcoxon test was used to analyze for differences between serum zinc in thalassemia patients and controls. Spearman's correlation test was used to analyze for a possible correlation between ferritin and serum zinc in thalassemia patients. Results There were 34 patients with thalassemia and 34 healthy control subjects. The median serum zinc was 119.34 μg/dL (IQR=71.27) in the thalassemia group and 120.08 μg/dL (IQR=26.28) in the control group (P=0.36). There was no significant correlation between serum ferritin and zinc in thalassemica children (r=-0.023; P=0.895). Conclusion There is no difference in serum zinc levels between thalassemic children and healthy controls. There is no correlation between serum ferritin and zinc in thalassemica children. [ABSTRACT FROM AUTHOR]

Background. Extramedullary hematopoiesis (EMH) is common in non-transfusion-dependent thalassemia (NTDT) patients. Clinical presentations of EMH vary as MRI screening is not feasible. Hence, serum biomarkers are used to predict the risk of EMH. Materials and Methods. 52 NTDT patients, including 26 EMH (+) and 26 EMH (-), together with 26 healthy controls, were enrolled in this case-control study from 2013 to 2016. EMH was confirmed by computed tomography or MRI. Demographic, transfusion, genetic, laboratory, and liver iron concentration (LIC) data, as well as clinical complications, were analyzed. Results. EMH (+) patients had significantly higher serum ferritin (SF), growth differentiation factor 15 (GDF15), and erythropoietin (EPO) levels compared with EMH (-) patients and controls. The levels of erythroferrone (ERFE), hepcidin, and sTfR did not differ significantly between EMH (+) and EMH (-) patients (p>0.05). In NTDT patients, serum ERFE was not related to SF, LIC, hepcidin, sTfR, EPO, GDF15, and Hb levels. GDF15, EPO concentrations, and GDF15 to sTfR and GDF15 to EPO ratios are able to determine the presence of EMH with considerable sensitivity and specificity. Conclusions. GDF15, EPO, and GDF15 to EPO and GDF15 to sTfR ratios are potential biomarkers for the early prediction of NTDT in patients who are at risk for EMH. [ABSTRACT FROM AUTHOR]

Thalassemia awareness among the youth is vital for policy- making to reduce the disease burden in our country. A descriptive cross-sectional study was conducted via simple random sampling technique for which data was collected from May 2020 to May 2021 through Google forms. Results showed that out of a total of 394 non-medical university students, the majority, i.e. 265 (67.3%), were not aware of prenatal screening. Majority, i.e. 117 (29.7%), agreed that the couple should be screened before marriage, and 190 (48.2%) strongly agreed, while 46 (11.7%) had no knowledge. Students, however, believed premarital screening was either unavailable, not possible, or expensive. Other reasons included custom and culture of arranged marriages and religious reasons. The query that if both the parents are carriers and the foetus has thalassemia major should they have an abortion, showed mixed results. The key to controlling thalassemia is awareness of future parents.

Introduction: Thalassemia is the most common single-gene disorder in India. Hence, care of these patients becomes a priority issue. Objectives: This study was done to assess the clinical presentations and management practices in thalassemia. Materials and Methods: Case sheets of patients with thalassemia admitted over the past 10 years from 2005 to 2014 were examined and recorded in a validated pro forma. Results: Of the total 183 cases, 179 (97.8%) were of beta thalassemia major, 3 (1.6%) of beta thalassemia intermediate, and 1 (0.6%) of beta thalassemia minor category. The median age at diagnosis was 1 year. Hardly, one-fourth of the cases were diagnosed in the first 6 months. Majority of cases were under-fives 58 (31.7%) and were males 116 (63.4%). Fever was the most common presenting symptom 34 (18.6%). Pallor 179 (97.8%) followed by hepatomegaly 172 (94%) were the most common signs. Bone deformities were reported in 13 (7.1%) cases. Among the under-fives, more than one-third were underweight and more than half were stunted. The mean posttransfusion value of hemoglobin after 1 year of transfusion among cases was 10 ± 1.6 g percent. Iron chelation therapy using desferrioxamine was given to 51 (27.9%) cases. The mean age of starting this therapy was 11.1 ± 8.2 years. Splenectomy was done in 4 cases, all of them being cases of beta thalassemia major. The mean age while performing splenectomy was 10.7 ± 4.8 years. Lenticular opacity was present among greater proportion of thalassemia cases on treatment with desferrioxamine (P = 0.022). Conclusion: Several complications were identified among thalassemia cases. A multidisciplinary care approach is therefore required for solving these problems. [ABSTRACT FROM AUTHOR]

BACKGROUND: One-tube osmotic fragility test (OFT) is widely used for screening thalassemia traits. Interobserver variation may occur with 0.36% NaCl-based OFT due to the naked eye result reading style. PURPOSE: The purpose of this study was to establish and evaluate the novel numerical OFT-based parameter, so-called hemolysis area (HA), in screening thalassemia traits. MATERIALS AND METHODS: The portable spectrophotometer was invented capable of calculating the HA values. The HA values were then compared among 69, 156, and 19 blood samples having positive, negative, and suspicious 0.36% NaCl-based OFT results, respectively; 109 and 135 blood samples having mean corpuscular volume (MCV) ≤80 fL and >80 fL, respectively; and 138 and 106 blood samples having mean corpuscular hemoglobin (MCH) ≤27 pg and >27 pg, respectively. In addition, the HA values were compared in 166 blood samples having different globin gene genotypes. Finally, the HA cutoff value was determined by receiver operation curve (ROC) analysis. RESULTS: The HA values in samples having positive, suspicious, and negative 0.36% NaCl-based OFT were 33.3 ± 14.4, 42.9 ± 10.5, and 65.3 ± 13.4, respectively; in sample having MCV ≤80 fL and >80 fL were 43.1 ± 19.6 and 63.8 ± 14.5, respectively; and in samples having MCH ≤27 pg and >27 pg were 46.7 ± 20.1 and 64.8 ± 14.2, respectively. The HA values in normal, hemoglobin E, SEA-a thalassemia 1, and β-thalassemia traits were 67.1 ± 12.6, 36.4 ± 13.9, 20.2 ± 4.8, and 18.6 ± 1.1, respectively. All were significantly different. ROC analysis established 52.4 as the HA cutoff that had comparable effectiveness to the conventional screening tests. CONCLUSION: The new HA value was effective and could be an alternative choice for screening thalassemia traits. [ABSTRACT FROM AUTHOR]

Introduction: Thalassemia could interfere with some assays for haemoglobin A1c (HbA1c) measurement, therefore, it is useful to be able to screen for thalassemia while measuring HbA,c. We used Capillarys 2 Flex Piercing (Capillarys 2FP) HbA1c programme to simultaneously measure HbA1c and screen for thalassemia. Materials and methods: Samples from 498 normal controls and 175 thalassemia patients were analysed by Capillarys 2FP HbA1c programme (Sebia, France). For method comparison, HbA1c was quantified by Premier Hb9210 (Trinity Biotech, Ireland) in 98 thalassaemia patients samples. For verification, HbA,c from eight thalassaemia patients was confirmed by IFCC reference method. Results: Among 98 thalassaemia samples, Capillarys 2FP did not provide an HbA,c result in three samples with HbH due to the overlapping of HbBart's with HbA1c fraction; for the remaining 95 thalassaemia samples, Bland-Altman plot showed 0.00 ± 0.35% absolute bias between two systems, and a significant positive bias above 7% was observed only in two HbH samples. The HbA,c values obtained by Capillarys 2FP were consistent with the IFCC targets (relative bias below ± 6%) in all of the eight samples tested by both methods. For screening samples with alpha (α-) thalassaemia silent/trait or beta (β-) thalassemia trait, the optimal HbA2 cut-off values were ≤ 2.2% and > 2.8%, respectively. Conclusions: Our results demonstrated the Capillarys 2FP HbA1c system could report an accurate HbA1c value in thalassemia silent/trait, and HbA2 value (< 2.2% for a-thalassaemia silent/trait and > 2.8% for (3-thalassemia trait) and abnormal bands (HbH and/or HbBart's for HbH disease, HbF for (3-thalassemia) may provide valuable information for screening. [ABSTRACT FROM AUTHOR]

Thalassemia traits (TTs) and iron deficiency anemia (IDA) are the most common disorders of hypochromic microcytic anemia (HMA). The present study aimed to differentiate TTs from IDA by analyzing discrimination formulas and provides comprehensive data of hemoglobin disorders prevalent in Pakistan. Among 12 published discrimination formulas, 6 formulas--MI, EF, G&K, RDWI, R, and HHI--were the most reliable to discriminate TTs from IDA. The failure cutoff values were improved by the random forest (RF) decision-tree approach. Moreover, the Shine and Lal (S&L) formula, which completely failed to discriminate IDA from TTs with original cutoff value (<1530), improved with the use of new proposed cutoff value (<1016) and was found to successfully discriminate all cases of TTs from those with IDA. In addition, 2 newly proposed formulas discriminated TTs from IDA more reliably than the original 12 formulas assessed. The proposed formulas could play a crucial role for clinicians to discriminate between TTs and IDA. [ABSTRACT FROM AUTHOR]

Introduction: Molecular screening of Thalassemia is a burning issue especially for developing country where birth rate is high and most of the victims are from rural and from economically downtrodden part of the society. Methods: The present study reports about the molecular diagnosis and pattern identification of Thalassemia carrier parents and females, who are in certain condition to determine their genotype of Chorionic Villi sample (CVS) to combat birth of new thalassemia baby. Result: Data suggest for the year 2014 and 15 that IVS 1-5(G-C) genotype heterozygous is the most prevalent for each year and affected CVS are either IVS 1-5(G-C) homozygous or compound heterozygous cases containing IVS 1-5(G-C). Bihar, Hooghly, Kolkata, North 24 Parganas, South Dinajpur and North Dinajpur is showing significant difference. Few regions are with a little laxity of patient flow for prenatal diagnosis. Conclusion: This data is useful to make a genetic micro map of West Bengal and also gives the vivid distribution of different Thalassemia gene across the state. [ABSTRACT FROM AUTHOR]

Context.--Spurious platelet counts from automated methods have been reported in patients with abnormal red blood cells. However, there is no specific study regarding performance of platelet counts by automated methods in patients with thalassemia. Objective.--To investigate the performance of automated platelet counts, including impedance (PLT-I) and optical fluorescent (PLT-O and PLT-F) methods, and compare them with the international reference method (IRM) for platelet counting in patients with thalassemia. Design.--Two hundred forty-nine thalassemia specimens from various subtypes were examined. PLT-I, PLTO, and PLT-F from a Sysmex XN analyzer were evaluated and compared against the IRM. Demographic data, platelet counts, and red blood cell parameters are shown. Comparability between evaluated methods and IRM, as well as test characteristics, is presented. Factors involving inaccurate PLT-I were analyzed. Results.--Specimens with platelet counts ranging from 31x10³/µL to 932x10³/µL were included. Most patients were patients with thalassemia major. Correlation between PLT-I and IRM was lower than that of the other methods in overall patients. PLT-O and PLT-F were correlated to IRM when classifying patients according to clinically significant platelet ranges. All automated methods had acceptable sensitivities; however, specificity of PLT-I was low for diagnosis of thrombocytopenia. High RDW-CV (red blood cell distribution width--coefficient of variation) was an independent factor of inaccurate PLT-I measurement. Conclusions.--Among the evaluated methods, PLT-I was the method least correlated to IRM, with PLT-O and PLT-F comparable to IRM in patients with thalassemia. Optical platelet counts and careful blood smear examination are recommended alternative platelet counting methods, depending on the clinical setting. [ABSTRACT FROM AUTHOR]

Background: β-Thalassemia is the most prevalent genetic disorder in India. Its traits and coinheritance vary from mild to severe conditions, resulting in thalassemia minor, intermediate, and major, depending upon many factors. Purpose: The objective of this study was to identify the incidence of β-thalassemia traits, their coinheritance, and mutations, as well as to support the patients already diagnosed with β-thalassemia in East-Western Indian population for better management. Patients and methods: Seventy-five referral cases for β-thalassemia were analyzed for various β-thalassemia traits, heterozygosity, and homozygosity conditions. Blood phenotypic parameters using cell counter and capillary electrophoresis were investigated. Analyses of eight common mutations of thalassemia in India were carried out using polymerase chain reaction-amplification refractory mutation system, end point polymerase chain reaction, and DNA sequencing methods. Results: Of these (75) referral cases from East-Western Indian region, 68 were positive for β-thalassemia (90.67%). The majority of case types were of β-thalassemia minor (49, 65.33%), followed by HbE traits (6, 8.0%) and β-thalassemia major, including heterozygous and homozygous (5, 6.66%; 4, 5.33%) types and then HbE homozygous (2, 2.66%), as well as one each of the HbE/β-thalassemia and HbD/β-thalassemia (1, 1.34%) combination. Mutation analysis also revealed that the highest frequency of mutation was c.92+5G>C (41, 60.29%) followed by deletion 619bp (9, 13.23%) and c.79G>A (8, 11.76%) in our study group. Five cases (nos. 24, 27, 33, 58, and 71) exhibited coinheritance between β0/β+ (2), β0/β D (1), and c.124_127delTTCT/β+ or β0 (2) affecting the Rajasthani and Gujarati populations in our study of the Western region of India. Conclusion: We strongly recommend these Western populations for genetic screening before adopting reproductive technologies and interracial marital relations. [ABSTRACT FROM AUTHOR]

The β-thalassemias are genetic disorder caused by more than 200 mutations in the β-globin gene, resulting in a total (β0) or partial (β+) deficit of the globin chain synthesis. The most frequent Mediterranean mutations for β-thalassemia are: β039, β+IVSI-110, β+IVSI-6 and β0IVSI-1. Several molecular techniques for the detection of point mutations have been developed based on the amplification of the DNA target by polymerase chain reaction (PCR), but they could be labor-intensive and technically demanding. On the contrary, TaqMan® genotyping assays are a simple, sensitive and versatile method suitable for the single nucleotide polymorphism (SNP) genotyping affecting the human β-globin gene. Four TaqMan® genotyping assays for the most common β-thalassemia mutations present in the Mediterranean area were designed and validated for the genotype characterization of genomic DNA extracted from 94 subjects comprising 25 healthy donors, 33 healthy carriers and 36 β-thalassemia patients. In addition, 15 specimens at late gestation (21–39 gestational weeks) and 11 at early gestation (5–18 gestational weeks) were collected from pregnant women, and circulating cell-free fetal DNAs were extracted and analyzed with these four genotyping assays. We developed four simple, inexpensive and versatile genotyping assays for the postnatal and prenatal identification of the thalassemia mutations β039, β+IVSI-110, β+IVSI-6, β0IVSI-1. These genotyping assays are able to detect paternally inherited point mutations in the fetus and could be efficiently employed for non-invasive prenatal diagnosis of β-globin gene mutations, starting from the 9th gestational week. [ABSTRACT FROM AUTHOR]

Thalassemia is a monogenic autosomal recessive disorder caused by mutations, which lead to abnormal or reduced production of hemoglobin. Ineffective erythropoiesis, hemolysis, hepcidin suppression, and iron overload are common manifestations that vary according to genotypes and dictate, which diagnosis and therapeutic modalities, including transfusion therapy, iron chelation therapy, HbF induction, gene therapy, and editing, are performed. These conventional therapeutic methods have proven to be effective, yet have several disadvantages, specifically iron toxicity, associated with them; therefore, there are demands for advanced therapeutic methods. Nanotechnology-based applications, such as the use of nanoparticles and nanomedicines for theragnostic purposes have emerged that are simple, convenient, and cost-effective methods. The therapeutic potential of various nanoparticles has been explored by developing artificial hemoglobin, nano-based iron chelating agents, and nanocarriers for globin gene editing by CRISPR/Cas9. Au, Ag, carbon, graphene, silicon, porous nanoparticles, dendrimers, hydrogels, quantum dots, etc., have been used in electrochemical biosensors development for diagnosis of thalassemia, quantification of hemoglobin in these patients, and analysis of conventional iron chelating agents. This review summarizes the potential of nanotechnology in the development of various theragnostic approaches to determine thalassemia-causing gene mutations using various nano-based biosensors along with the employment of efficacious nano-based therapeutic procedures, in contrast to conventional therapies.

Competing Interests: None

Objective. To assess body composition in adult male and female patients with thalassemia major by dual-energy X-ray absorptiometry (DXA) and to compare the findings with a group of healthy age-matched controls. Methods. Our study group included sixty-two patients (27 males, mean age 36 years, and 35 females, mean age 36.4 years) and fifteen age-matched healthy controls. All patients had an established diagnosis of thalassemia major and followed a regular blood transfusion scheme since childhood and chelation treatment. Fat, lean, and bone mineral density (BMD) were assessed with dual-energy X-ray absorptiometry. Ferritin levels and body mass index of all patients and controls were also recorded. Student t-test and Wilcoxon test were performed and statistical significance was set at p<0.05. Results. BMD and whole body lean mass are lower in both male and female adult patients compared with controls (p<0.01 in both groups), whereas whole body fat mass was found to have no statistically significant difference compared to controls. Regional trunk fat around the abdomen was found to be lower in male patients compared to controls (p=0.02). Conclusion. Severe bone loss and diminished lean mass are expected in adult male and female patients with thalassemia major. Fat changes seem to affect mainly male patients. [ABSTRACT FROM AUTHOR]

The prevalence of β-thalassemia (β-thal) carriers in Turkey varies according to region but in general it is 2.0%. Çanakkale is a city in the Aegean region of Turkey but no study about β-thal frequency in Çanakkale has been published to date. In this study, we aimed to investigate the frequency of β-thal mutations in this province. A total of 4452 couples (8904 individuals) applied for premarital thalassemia scans at the Çanakkale State Health Directorate Laboratory between January 2008 and June 2012 and scanning was done with high performance liquid chromatography (HPLC). Of 125 β-thal carriers seen at the Medical Genetics Clinic, Çanakkale Onsekiz Mart University, Çanakkale, Turkey, for genetic counseling, 46 participated in the study. The remaining 79 patients could not be reached. The prevalence for β-thal carriers in Çanakkale was identified as 1.4% (125/8904). One couple were both β-thal carriers. β-Globin gene analysis of 46 carriers found the total frequency of the three most common mutations was 45.6%. These mutations were found to be HBB: c.93-21G>A [IVS-I-110 (G>A)], 26.08% (12/46); HBB: c.17_ 18delCT [codon 5 (-CT)], 10.85% (5/46); HBB: c.20delA [codon 6 (-A)] 8.69% (4/46). This is the first report on the frequency and mutation profiles of β-thal for Çanakkale. The incidence of β-thal carriers in Çanakkale is below the average for Turkey. The most frequently observed mutation profile and rate of β-thal in our region is different from the other regions of Turkey. [ABSTRACT FROM AUTHOR]

Background: The most common microcytic and hypochromic anemias are iron deficiency anemia and thalassemia trait. Several indices to discriminate iron deficiency anemia from thalassemia trait have been proposed as simple diagnostic tools. However, some of the best discriminative indices use parameters in the formulas that are only measured in modern counters and are not always available in small laboratories. The development of an index with good diagnostic accuracy based only on parameters derived from the blood cell count obtained using simple counters would be useful in the clinical routine. Thus, the aim of this study was to develop and validate a discriminative index to differentiate iron deficiency anemia from thalassemia trait. Methods: To develop and to validate the new formula, blood count data from 106 (thalassemia trait: 23 and iron deficiency: 83) and 185 patients (thalassemia trait: 30 and iron deficiency: 155) were used, respectively. Iron deficiency, β-thalassemia trait and α-thalassemia trait were confirmed by gold standard tests (low serum ferritin for iron deficiency anemia, HbA2 > 3.5% for β-thalassemia trait and using molecular biology for the α-thalassemia trait). Results: The sensitivity, specificity, efficiency, Youden's Index, area under receiver operating characteristic curve and Kappa coefficient of the new formula, called the Matos & Carvalho Index were 99.3%, 76.7%, 95.7%, 76.0, 0.95 and 0.83, respectively. Conclusion: The performance of this index was excellent with the advantage of being solely dependent on the mean corpuscular hemoglobin concentration and red blood cell count obtained from simple automatic counters and thus may be of great value in underdeveloped and developing countries. [ABSTRACT FROM AUTHOR]

Objective During thalassemia screening, a previously unidentified α2 gene variation in α-globin gene cluster was isolated. This variation was distinct from other variations known to confer thalassemia as assessed by conventional thalassemia genotype analysis. Because the sample in the thalassemia screening was positive (MCV = 83.6 fL, MCH = 26.1 pg/cell, Hb = 11.3 g/dL), further analysis was required. Material and methods MLPA (multiplex ligation-dependent probe amplification) and sequencing were used for analysis, and a qPCR system was designed for the frequency study. Results The MLPA result showed that there was a mutation or small fragment deletions between 34247 (160 bp probe) and 34618 (196 bp probe) in α-globin gene cluster (NG_000006.1). Through sequencing, this variation was identified as HBA2: c.301-24delGinsCTCGGCCC. The gene polymorphisms similar to HBA2:c.301-24delGinsCTCGGCCC are α 121 and α 212. Since α 212 is unrelated to microcytosis, and the structure of HBA2: c.301-24delGinsCTCGGCCC is similar to α 212 , this change is more appropriately considered as a polymorphism. The allele frequency of HBA2: c.301-24delGinsCTCGGCCC is 0.184% in this region. Conclusions There is a certain ratio for HBA2:c.301-24delGinsCTCGGCCC carriers among the Chinese population. The HBA2:c.301-24delGinsCTCGGCCC variant results in an abnormal result from MLPA analysis. Investigators performing thalassemia screening in Guangxi region should be aware of the HBA2:c.301-24delGinsCTCGGCCC variant to avoid misinterpretation of the MLPA results. [ABSTRACT FROM AUTHOR]

Single-cell optical analysis of red blood cells provides information on the cellular hemoglobin concentration and volume of red cells. We evaluated the reliability of the typical profiles of the cytogram hemoglobin concentration/volume (Mie Map), produced by the CELL-DYN® Sapphire analyzer (Abbott Diagnostics, Santa Clara, CA, USA) in the discrimination of iron deficiency anemia (IDA) and thalassemia trait. A total of 380 patients with microcytic anemia were studied: 220 with IDA, 101 β-thalassemia trait, 30 β-thalassemia trait with concomitant iron deficiency, 29 α-thalassemia trait. Three professionals reviewed the Mie maps, with no information regarding the disease of the patient. The observers made a presumptive diagnosis (genetic or acquired anemia) and the percentages of correct classifications were recorded. IDA showed broad shaped shift of the cytogram while carriers presented narrow clustering in the lower microcytic area: 100% IDA were correctly classified and 96-82% of carriers were recognized. Visual inspection of the Mie map reveals different profiles in IDA and thalassemia trait; those patterns are in concordance with the numerical data Mie map helps in the evaluation of large amounts of data. [ABSTRACT FROM AUTHOR]

The article discusses the use of the glucagon stimulation test (GST) in the diagnosis of central adrenal insufficiency (CAI) in patients with thalassemia major (TM).

Background and Objectives: In newborns and infants during their first year of life, there is a dynamic change in the fraction of hemoglobin (Hb). To apply Hb analysis as a phenotypic diagnosis of thalassemia in newborns and infants, we need normal values of each Hb fraction for reference. Methods: Seventeen cord bloods from normal deliveries were collected for analysis. One hundred and thirty-seven infants from the pediatric outpatient clinic were recruited and were categorized by their ages into a series of short periods (month±2 weeks). Both alpha and beta thalassemia carriers detected were excluded. Samples with an Hb level less than 10.0 g/dL were also excluded. The proportion of Hb A (α2β2), A2 (α2δ2), and F (α2γ2) was obtained from high-performance liquid chromatography and analyzed according to its categorized periods. Results: There were 90 (58.4%) specimens left for evaluation. The percentage of Hb A, A2, and F gradually changed with increasing age. The percentage of Hb A was 21.14±7.04% (mean±SD) in cord blood and increased substantially to 83.38±1.31% at the sixth month. The level was sustained thereafter. The incremental pattern of Hb A2 was similar to Hb A. The value was 0.32±0.19% at the beginning and reached a plateau with 2.78±0.25% at the sixth month. The percentage of Hb F started at 78.39±7.59% in cord blood and decreased rapidly in the first 6 months. Conclusions: The data possibly can be applied as quick guidance for interpretation of Hb analysis in newborns and infants during their first year of life. [ABSTRACT FROM AUTHOR]

Moyamoya disease is an idiopathic, nonatherosclerotic, noninflammatory, chronic progressive cerebrovascular disease characterized by bilateral stenosis or occlusion of the arteries around the circle of Willis, typically the supraclinoid internal carotid arteries, followed by extensive collateralization, which are prone to thrombosis, aneurysm, and hemorrhage. Secondary moyamoya phenomenon or moyamoya syndrome (MMS) occurs in a wide range of clinical scenarios including prothrombotic states such as sickle cell anemia, but the association with other hemoglobinopathies is less frequently observed. We describe a case of a 25-year-old female with hemoglobin E-beta thalassemia who had a rare presentation of MMS in the form of choreoathetoid movements in the left upper and lower extremities. We describe this association, primarily to emphasize thalassemia as an extremely rare but a potential etiology of MMS. Since MMS is a progressive disease, it is important to diagnose and initiate treatment to prevent worsening of the disease and recurrence of stroke. [ABSTRACT FROM AUTHOR]

Background: Thalassemia trait (TT) and iron deficiency anemia (IDA) are the most common conditions of microcytic hypochromic anemia (MHA) in pregnant women. Accurate discrimination between TT and IDA is an important issue, and better methods are urgently needed. Although considerable RBC formulas and indices have been developed since 1973, distinguishing between IDA and TT is still a challenging problem due to the diversity of various anemic populations. To address this problem, we assessed the diagnostic function of 43 different differential formulas in patients with microcytic anemia by using accuracy measures and recommending a new log-based differential formula., Methods: The data of 430 pregnant women (229 with TT and 201 with IDA) were enrolled, and 44 formula performances were evaluated with receiver operating characteristic (ROC) analysis., Results: The newly introduced logarithm-based formula XS-1 performs better than the general discriminant index with sensitivity and specificity of 82.10 and 89.05, which are better than other formulas. In the pregnant population, the Shine and Lal and Roth..SVM. formulas have shown excellent performance, while other formulas showed poorer discriminative abilities in our study than in the original authors., Conclusion: The logarithm-based formula XS-1 can be used to screen thalassemia and iron deficiency anemia during the first trimester. Considering the particularity of pregnancy, medical personnel in different regions should choose a screening formula similar to that of the local region and population when identifying thalassemia in pregnancy. Any formula should be independently verified locally before use. For the convenience of the health care team and experimental scientists, a web-based tool has been established at http://yyy.yiyiy.top/XS-1/ by which users can easily get their desired screening test result without going through the underlying mathematical and computational details., (© 2023. The Author(s).)

Introduction. Cases with microcytosis not responding adequately to iron supplementation are diagnostic dilemma and have been reported to harbor alpha (α) thalassemia mutations. The aim of this study was to determine the common a globin gene deletions in cases with microcytic anemia. Methods Fifty four patients selected (22 females and 32 males) had microcytic anemia (MCV < 80 fl, Hb <12gm/dl) with raised TRBC (> 5M/mm3) but normal Hb HPLC. They had either low or normal Transferrin Saturation (TS). Gap-PCR for four common α-gene deletions (- α37, -α42, - -αSA and --αSEA) was done. Results Out of the total fifty-four cases nineteen (35.2%) cases were found to have α gene mutations; Three homozygous and sixteen heterozygous cases including -α3.7 deletions and a single case of -- α SA; but no -α4.2 and - SEA mutations were found. Conclusion α gene mutations can confound iron deficiency anemia, but no RBC indices, or a discriminant function can identify it is presence Molecular studies have to be resorted to. Gap PCR for common a thalassemia mutation including - α SA should be done even in the face of low iron stores in subjects who respond incompletely to iron supplementation. [ABSTRACT FROM AUTHOR]

Background: Thalassaemia is one of the most common inherited monogenic diseases worldwide with a heavy global health burden. Considering its high prevalence in low and middle-income countries, a cheap, accurate and high-throughput screening test of thalassaemia prior to a more expensive confirmatory diagnostic test is urgently needed., Methods: In this study, we constructed a machine learning model based on MALDI-TOF mass spectrometry quantification of haemoglobin chains in blood, and for the first time, evaluated its diagnostic efficacy in 674 thalassaemia (including both asymptomatic carriers and symptomatic patients) and control samples collected in three hospitals. Parameters related to haemoglobin imbalance (α-globin, β-globin, γ-globin, α/β and α-β) were used for feature selection before classification model construction with 8 machine learning methods in cohort 1 and further model efficiency validation in cohort 2., Results: The logistic regression model with 5 haemoglobin peak features achieved good classification performance in validation cohort 2 (AUC 0.99, 95% CI 0.98-1, sensitivity 98.7%, specificity 95.5%). Furthermore, the logistic regression model with 6 haemoglobin peak features was also constructed to specifically identify β-thalassaemia (AUC 0.94, 95% CI 0.91-0.97, sensitivity 96.5%, specificity 87.8% in validation cohort 2)., Conclusions: For the first time, we constructed an inexpensive, accurate and high-throughput classification model based on MALDI-TOF mass spectrometry quantification of haemoglobin chains and demonstrated its great potential in rapid screening of thalassaemia in large populations.Key messagesThalassaemia is one of the most common inherited monogenic diseases worldwide with a heavy global health burden.We constructed a machine learning model based on MALDI-TOF mass spectrometry quantification of haemoglobin chains to screen for thalassaemia.