Beta-thalassemia Trait Research Articles

Heterozygous Beta-Thalassaemia in Pregnancy: Two Rare Causes of Severe Fetal Anemia Requiring Intrauterine Blood Transfusions.

In this article, we present two cases of severe fetal hemolytic anemia based on a beta-thalassaemia trait inherited from a single parent. These cases, presented at 20 and 28weeks' gestation, necessitated intra-uterine blood transfusions. This occurrence is remarkable because it challenges the common assumption that beta-thalassaemia typically has no prenatal implications regarding fetal anemia. Both fetuses inherited a rare heterozygous mutation from their mother, resulting in gamma-thalassaemia-related anemia. In the first case, the anemia was related to a deletion in the beta locus control region (βLCR) and in the second case, a deletion on chromosome 11p15.4 was the cause. These mutations not only affect the beta chain production, but also the gamma chain production, leading to a reduction in the synthesis of HbF, ineffective erythropoiesis and consequently, perinatal hemolytic anemia. Clinicians should be vigilant regarding these rare mutations in families with a history of beta-thalassaemia as the fetal clinical consequences can be severe and intra-uterine blood transfusions may prove life-saving for these fetuses.

Critical appraisal of the utility of 13 discriminant formulas for distinguishing beta thalassemia trait from iron deficiency in patients with microcytic anemia and the introduction of a new formula in a USA population

Abstract Iron deficiency anemia (IDA) and beta thalassemia trait (ß-TT) are two frequent causes of microcytic anemia that often pose a diagnostic dilemma with implications for management. Many discriminant formulas have been proposed for distinguishing these two conditions. However, there is a need for independent verifications of these formulas to determine their applicability to other populations, particularly more diverse populations, as seen in the United States. To date, no study has been performed in the United States to evaluate the utility of these formulas in distinguishing both conditions. The study objective was to evaluate the utility and predictive values of 13 discriminant indices and formulas for distinguishing ß-TT from IDA in a US population. We investigated 13 formulas comprising only hematologic parameters available on all analyzers. The investigational population consisted of 238 patients with microcytic anemia; 165 with a hemoglobin electrophoresis diagnosis of ß-TT and 73 diagnosed with IDA by clinician review or iron studies. The study population comprised 55% black or African American, 35% White, 5% Asian, 1.2% Native American, and 2.5% unidentified. Receiver operating characteristic curves were employed to evaluate the diagnostic performances of the formulas. All investigated formulas had poor sensitivities but high specificities. The three best-performing indices or formulas from those previously proposed for distinguishing ß-TT from IDA were the RBC (sensitivity 62.2%, specificity 87.1%), Green and King (MCV2×RDW/100 hemoglobin, Hb) with a sensitivity of 65.4% and specificity of 82.6%, and Wongprachum et al. (MCV×RDW/RBC) – 10 Hb) with a sensitivity of 63.6% and specificity of 82.6%. Areas under the curve (AUCs) were 0.68 for the RBC and, 0.67 for both Green and King and Wongprachum formulas. The Youden indices were 0.49, 0.48, and 0.46, respectively. The Mentzer index had a sensitivity of 63.4%, specificity of 81.7% and Youden index of 0.45. We introduced a new formula comprising the sum of three of the most readily obtained red cell parameters (RBC + Hb + MCV). It had a Youden index of 0.95, sensitivity of 96.8, specificity of 98.0, and AUC of 0.97, significantly outperforming other formulas in our study population (p=0.00). This is the first study in the USA evaluating the utility of multiple indices for distinguishing ß-TT from iron deficiency anemia. The best performing formulas in other studies did not perform well in our population. This necessitated an introduction of a new formula that demonstrates excellent potential to address the unique diversity of the US population.

Reemergence of Hemoglobin Yukuhashi

Abstract The abnormal hemoglobin, Hb Yukuhashi, identified in Japan in 1963, exhibits slower migration compared to Hb A and is associated with target cells on peripheral smear. A similar hemoglobin, Hb Dhofar, is found in an Omani tribesman and is defined as a substitution of arginine for proline at the 58th amino acid position of the beta-globin chain. Despite both Yukuhashi and Dhofar seemingly arising from the same exonic point mutation, variations in expression were clarified through beta-globin gene amplification. Hb Dhofar, unlike Yukuhashi, was linked to a splice-site mutation at codon 29, explaining its reduced expression. Despite these hemoglobins’ structural alterations, their functional properties on a molecular level, including oxygen affinity and heme-heme interaction, remained largely unaffected. While mutations at codon 58 have been observed alongside other mutations in Hb Dhofar and Hb C-Ziguinchor, this case represents the first sequencing and report of a beta-globin gene mutation solely at codon 58, as only Yukuhashi’s protein coding region had been sequenced, not the whole gene. “Hemoglobin D” was detected on newborn screening of a male child with no other significant medical history or physical abnormalities. Capillary Electrophoresis and Cation-Exchange HPLC showed abnormal hemoglobin fractions, with 20.1% in the S Zone and 25.7% in the D-window, respectively. This led to a presumptive diagnosis of Hemoglobin Dhofar trait; however, discrepancies in hematologic parameters and relative hemoglobin levels were noted. Genetic testing of the Beta Globin gene confirmed a C to G substitution at codon 58 but lacked the characteristic codon 29 mutations associated with Hemoglobin Dhofar. The patient, was discovered to possess a mutation at codon 58 on the beta globin gene, a mutation not previously reported in isolation. In contrast to previous studies on Hb Dhofar, where variant Hb levels were lower and accompanied by abnormal RBC indices indicative of beta thalassemia trait, this case exhibited higher variant Hb levels with normal RBC indices, suggestive of a typical beta globin variant. The mutation at codon 58 did not significantly alter intermolecular interactions of the globin which may mean the variant is clinically asymptomatic in nature. Continued follow-up is necessary to confirm this suspicion, although initial assessments at 3 and 6 months of age showed normal RBC parameters. This case represents the first instance of an isolated mutation at codon 58 of the beta globin gene, emphasizing the need to consider this mutation in interpreting hemoglobinopathy screening results.

S4368 Atypical Presentation of Beta-Thalassemia Trait with Heterozygous H63D Mutation: Hemolysis, Iron Overload, and Liver Cirrhosis

S4368 Atypical Presentation of Beta-Thalassemia Trait with Heterozygous H63D Mutation: Hemolysis, Iron Overload, and Liver Cirrhosis

Genetic Study for Identifying Beta Thalassemia Trait in Relatives of Children with Beta Thalassemia Major.

The most common inherited illness, thalassemia, is thought to have a detrimental effect on public health, particularly in endemic areas. Children with beta thalassemia disease have several mutations. Prevention and premarital examination are still the most effective measures to lessen the burden of beta thalassemia. This study primarily aimed to determine the beta thalassemia carriers in relatives of beta thalassemia major children, the role of gene study in the confirmation of beta thalassemia trait diagnosis, and to detect the genetic defect in the relatives of beta thalassemia major children. The cross-sectional study was conducted on 109 healthy children, aged between six months and 18 years, who were the relatives (second and fourth degree) of beta thalassemia major cases. Gene screening, using the amplification refractory mutation system (ARMS) polymerase chain reaction (PCR), covered the most common 22 alleles in the Mediterranean region, and was successful in detecting 61.5% of beta-globin chain mutations of studied participants, in addition to high prevalence (34.8%) of beta thalassemia carriers among the relatives of beta thalassemia children. The beta thalassemia carrier rate was found to be highly prevalent among relatives of beta thalassemia major children. Despite the accuracy of gene screening in the detection of beta thalassemia carriers, the use of the most common 22 alleles can only detect 61.5% of carriers; hence, the value of tested gene study is still limited in the detection of carrier rates.

Prevalence of hemoglobinopathies detected by high performance liquid chromatography in tertiary care centre, Kota, Rajasthan

Background: Hemoglobinopathies are the most common heterogeneous group of monogenetic disorder in the world. Their prevalence varies with geographical regions. India is developing country and many studies have shown a significant burden of hemoglobinopathies in India. Our aim is to estimate prevalence of various hemoglobinopathies in our region. Methods: The present study was conducted at the department of pathology, Government Medical College, Kota on patients referred for antenatal or voluntary premarital checkup, patients with clinical history and complete blood count (CBC) suggestive of hemolytic anemia, and family members of known cases of hemoglobinopathies. Transfusion-dependent patients were also included. However, patients with history of blood transfusion within the last 1 month were excluded. EDTA samples were used for CBC using 6-part differential cell counter and high-performance liquid chromatography (HPLC) using BIORAD D10 analyzer. The results were tabulated and analyzed. Results: Of the 226 cases studied, 139 (61.5%) were females and 87 (38.5%) were males. Most common age group was 21 to 30 years. The number of thalassemia traits were 26 (11.5%), sickle cell traits were 7 (3.1%), sickle cell homozygous was 1 (0.4%), compound heterozygous for sickle cell and thalassemia were 2 (0.9%), while the remaining 190 patients (84.07%) were found to have normal HPLC, with presence or absence of nutritional deficiency. Conclusions: In our study, we found a high prevalence of hemoglobinopathies among patients. The most common disorder detected was beta thalassemia trait. Most of the hemoglobinopathies found in our study could be accurately quantified by HPLC which is a rapid, sensitive, and reproducible method for the detection of different hemoglobinopathies.

Beta-thalassemia intermedia due to a complex alpha-globin rearrangement and a heterozygous beta thalassemia mutation.

The alpha-thalassaemia alleles are very frequent in the world's population. The main molecular mechanism is a large deletion with the loss of one or two alpha genes. Another type of rarer abnormality exists: the gain of alpha genes. The consequence of a gain is an overproduction of alpha-globin chains, which aggravates a beta-thalassaemia trait into an intermedia phenotype (non-transfusion-dependent thalassaemia, NTDT). Here, we report the case of a young girl referred for a beta-NTDT with a combination never described in the literature: a heterozygous beta-thalassaemia mutation associated with a copy number gain of the alpha-globin locus and -alpha 3.7 deletion on the same allele.

Matos-Carvalho Index as a Comparison to other Discriminant Indexes in Initial Beta Thalassemia

Background Microcytic hypochromic anemia is the most common type of anemia found in Beta Thalassemia Trait and Iron Deficiency Anemia, posing a diagnostic challenge due to their similar presentations. Diagnostic errors among them can lead to incorrect treatment, potentially resulting in fatal outcomes. In Indonesia HPLC (High Performance Liquid Chromatography) usage as gold standard for discrimination between these diseases are expensive. Discrimination indices offer an alternative for cheaper and effective initial screening. However, a comprehensive performance evaluation of those indices, such as Matos and Carvalho indices, alongside Mentzer index, Green and King index, England and Fraser index, RBC index, Shine and Lal index, and Srivastava index, has not been conducted in Indonesia. This study aims to determine the best discriminative performance index based on the highest Youden’s indes value between those seven indices. Methods Study consisted of 30 subjects of beta thalassemia trait and 35 subjects of iron deficiency anemia. Index calculations were performed using blood profile formulas and compared with gold standard test results to find each index sensitivity, specificity, and Youden’s index value. Results Matos and Carvalho indices exhibited superior discriminatory performance, achieving 80% sensitivity, 77.1% specificity, and a Youden's index of 57.14%. Among other indices, the RBC index demonstrated the highest sensitivity (90%), while the Green and King index excelled in specificity (97.14%). MCV and MCH values did not significantly differ between BTT and IDA groups. Conclusions The study's findings underscore the efficacy of Matos and Carvalho indices in discriminating BTT and IDA in this study population, highlighting their potential as valuable tools in initial screening efforts.

Coexistence of Iron Deficiency Anaemia (IDA) and Beta Thalassaemia Trait (B-TT)

Background: The WHO estimates that about 7% of the world population are thalassaemia trait and increasing number of cases are being detected. The world population of carrier of b thalassamia is reported to be more than 100 million. Bangladesh also lies in thalassaemic Belt. A conservative world health report estimates that 3% of our populations are carrier of b thalassaemia which means that there are 3-6 million of b thalassaemia are in Bangladesh. To manage thalassaemia and thalassaemia trait, our traditional concept is not to give iron or iron conaining food. But concomitant iron deficiency anaemia in thalassaemia trait patient may be fatal. Those patients should be evaluated by serum ferritin or by the iron profile and treatment should be supplemented with rational amount of iron. Methodology: This cross sectional observational study was carried out on 75 patients from 03 to 59 years of age of both sex of Beta Thalassaemia Trait, in the department of Medicine and Haematology of Dhaka Medical College Hospital (DMCH) and Bangabandhu Sheikh Mujib Medical University (BSMMU) from January, 2015 to December, 2015. The patients previously diagnosed as Beta Thalassaemia Trait was included in study population. Result: In this study out of 75 Beta Thalassaemia Trait patients, 21 had evidence of Iron Deficiency Anaemia (IDA) and 54 patiens had no evidence of IDA. Thus the frequency of coexistent Beta Thalassaemia Trait and IDA in this study is 28%. The mean Hb concentration was 9.66 gm/dL (±1.54) which is 8.48 gm/dL (±1.43) and 10.12 gm/dL(±1.34) in Beta Thalassaemia Trait with IDA patients and Beta Thalassaemia Trait without IDA patients respectively. So the Hb concentration is significantly lower in b-TT with IDA patients than those without IDA (p-value < 0.001). The mean of Hb A2 level was 4.87(%) (±0.54) which is 4.44(%) (±0.40) and 5.03(%) (±0.50) in Beta Thalassaemia Trait with IDA patients and Beta Thalassaemia Trait without IDA patients respectively. So the Hb A2 level is significantly lower in Beta Thalassaemia Trait with IDA patients than those without IDA (p-value < 0.001). Conclusion: From this study, it could be concluded that the frequency of IDA in Beta Thalassaemia Trait is about 28%. The degree of anaemia is more severe and the level of Hb A2 is much lower in Beta Thalassaemia Trait with IDA patients than Beta Thalassaemia Trait without IDA. J Dhaka Med Coll. 2022; 31(2) : 182-186

Distinguishing Iron Deficiency Anemia From Beta-Thalassemia Trait: Comparative Analysis of CRUISE Index and Other Traditional Diagnostic Indices.

Introduction Iron deficiency anemia and beta-thalassemia trait are two common and important differentials of microcytic hypochromic anemia. Various discrimination indices using two or more common complete blood cell count (CBC) parameters have been used to distinguish between the two since1973. Recently, a new discriminant index, the CRUISE index, was proposed in the year 2019. The efficacy of various older indices along with the CRUISE index was evaluated for patients in our geographical area. Materials and method Ours was a laboratory-based, cross-sectional study where 100 patients, based on inclusion and exclusion criteria, with microcytic hypochromic anemia were evaluated for CBC parameters along with serum ferritin and hemoglobin-high performance liquid chromatography (Hb HPLC). A total of eight discrimination indices namely, Mentzer, Srivastava, Shine & Lal, Green & King, RDWI, England & Fraser, Kerman I and CRUISE index were used and evaluated for their diagnostic efficacy using different statistical parameters. ROC curves were obtained and a new cut-off value was proposed for our population. Data was analysed using Microsoft Excel (Microsoft® Corp., Redmond, WA, USA) and SPSS v29.0.2.0 (20) (IBM Corp., Armonk, NY, USA). Results Out of the total 100 cases, 39 were beta-thalassemia trait and 61 were iron deficiency anemia cases. The average age was 36.7 (±12.7 SD) years. Among the 73 females, 43 were diagnosed as iron deficiency anemia (IDA) and 30 as beta-thalassemia trait (BTT) cases. Among the 27 males, 18 were diagnosed as IDA and nine as BTT cases. The mean values were significantly lower in IDA patients for mean corpuscular volume (MCV) (p=.008), mean corpuscular haemoglobin (MCH) (p=.003), and mean corpuscular haemoglobin concentration (MCHC) (p=.003) and significantly higher for red cell distribution width (RDW) (p=.020). The mean ferritin levels in cases of IDA were 7.61 (±3.75) mcg/L and in BTT were 87.09 (±66.77 SD) mcg/L. The mean HbA2 levels in IDA cases were 2.75% (±0.41% SD) and BTT cases were 5.57% (±0.73% SD). CRUISEindex revealed the highest AUC (0.934), YI (76.21) and accuracy (90%) followed by the Mentzer index with a diagnostic accuracy of 81%. Shine & Lal index revealed the lowest AUC (0.710), YI (3.28) and accuracy (41%). Conclusion CRUISE index, which was recently proposed, was ranked 1st in terms of AUC, YI, and accuracy and was considered 2nd best in terms of sensitivity for differentially diagnosing the two conditions. Mentzer index, a commonly used index, also revealed a high diagnostic accuracy in our study for differentiating BTT from IDA. CRUISE index being a novel index, more research work needs to be carried out in various other geographical setups to evaluate the efficacy of this index.

Assessing NESTROFT as a preliminary screening tool for thalassemia in the Malayali tribes of Dharmapuri district, Tamil Nadu, India.

Mutations affecting transcription, translation, or beta-globin stability, among other stages of beta-globin production, cause beta-thalassemia. Beta-thalassemia results in a high red blood cell count with a low mean corpuscular volume (60-70fl) and mean corpuscular hemoglobin (19-23pg), and Naked Eye Single Tube Red Cell Osmotic Fragility Test (NESTROFT) is recommended for mass screening of populations. Among tribals in Dharmapuri district, this cross-sectional analysis evaluated the efficacy of RBC and NESTROFT against HPLC, regarded as the gold standard, in a study involving 484 subjects. Findings indicated that out of the 484 samples, 73 tested positive for the beta-thalassemia trait through HPLC. The NESTROFT test demonstrated 87% sensitivity, 98.5% specificity, a positive predictive value of 99.3%, and a negative predictive value of 73.3%. In the multivariate analysis, NESTROFT and hemoglobin showed high significance with P values of 0.003 and 0.000, respectively. NESTROFT's high sensitivity is particularly noteworthy due to the absence of research among the Malayali tribes in the Dharmapuri district. Adoption of this preliminary test shows promise in detecting the disease at the local level, providing important information for early detection, especially considering the sizeable tribal population.

Beta-thalassemia trait associated with a heterozygous loss-of-function variant of SUPT5H in a Southern Chinese family

Beta-thalassemia trait associated with a heterozygous loss-of-function variant of <i>SUPT5H</i> in a Southern Chinese family

A New Formula Based on Simple Blood Indices to Differentiate Beta Thalassemia Trait from Iron Deficiency Anemia.

Thalassemia is an inherited blood disorder with a defect in the sufficient production of a protein called hemoglobin. We aimed to investigate the simple blood indices of patients with Beta Thalassemia Trait (BTT) and Iron Deficiency Anemia (IDA) to propose a new formula using logistic regression for differentiate two characteristics from each other. Among the 702 records of the BTT Counseling Center (Khoy, Iran-2022), 292 cases (219 iron deficiency anemia (IDA) and 73 BTT) were eligible for the study. Blood indices such as RBC, HGB, HbA2 described and used to diagnose two types of participants. Blood indices had high multicollinearity that was modified. Logistic regression for blood indices fitted and goodness of fit indices with Area Under ROC curve (AUC) estimated. The average age of the participants was 24.56 yr. The status of Multicollinearity between independent variables was modified. The HGB, MCV, HbA2, and HbA variables were used in the model and only HbA2 status was significant (P<0.001). According to the output of the model, for each unit increase in HbA2, the chance of having BTT was about 8.5 times higher than IDA. The sensitivity, specificity, AUC curve, and accuracy of the final model were estimated to be 97, 72, 84, and 93%, respectively. A regression formula to differentiate BTT from IDA proposed. In studies related to the differentiation of the BTT from IDA, the presence of the HbA2 index in the model and prediction is very necessary.

Exploring the Clinical and Hematological Characteristics of Beta-Thalassemia Trait: A Comprehensive Analysis in a Tertiary Care Hospital Setting.

Beta-thalassemia is one of the most common inherited hematological diseases caused by more than 350 mutations in the β-globingene (HBB). Beta-thalassemia carrier or trait is associated with defects in one allele of the HBB gene. The majority of beta-thalassemia trait cases remain concealed in society and remain unnoticed as they are mostly asymptomatic or present with mild symptoms of anemia. There is a 25% chance of having children with beta-thalassemia major and a 50% chance of having carrier babies when two people with beta-thalassemia trait are married. Hence, it is important to identify the individuals with beta-thalassemia trait and provide counseling to understand the risks of pregnancy and its outcome. Aim To study the identification of beta-thalassemia trait cases along with their clinical findings and hematological correlation. Materials and methods Study Design This was a retrospective study conducted at Saveetha Medical College and Hospitalfor a period of four years from January 2020 to December 2023. Inclusion Criteria Age group more than 18 years, antenatal mother, cases of anemia who were refractory to iron treatment, and screening of family members in the positive cases of beta-thalassemia trait. Exclusion Criteria History of blood transfusion within three months was excluded. Data Collection A total number of 837 cases were screened to rule out the presence of beta-thalassemia trait/hemoglobin (Hb) variants. A 2 mL of intravenous blood samples were collected in an ethylene diamine tetraacetic acid (EDTA) vacutainer tube and processed in a Sysmex XN 1000 (Hyogo, Japan: Sysmex Corporation)automated hematology analyzer. The hematological parameters were analyzed. Statistical Analysis The study included both descriptive and analytical characteristics. Mean and standard deviation (SD) were calculated for all the hematological parameters. Beta-thalassemia trait was diagnosed with an HbA2 level of more than 4.0% through high-performance liquid chromatography (HPLC) analysis. Results Among the 837 samples studied for HPLC screening, 74 (8.8%) cases were found to have beta-thalassemia trait. The age group included was from 18 years to 56 years. Of 74 cases studied, 32(43%) were females and 42(57%) were males. Among the 74 cases studied, the Mentzer index <13 was seen in 58 (78%) cases and the Mentzer index >13 was seen in 16 cases (22%). Thirty-four cases (46%) of beta-thalassemia traits presented to the hospital with a history of fever for evaluation and antenatal screening accounted for 19 cases (26%). The mean red blood cell (RBC) count was 5.5 million/cu.mm; mean corpuscular volume (MCV) was 63.8 fL; mean corpuscular hemoglobin (MCH) was 19.6 pg; red cell distribution width coefficient of variation (RDW-CV) was 17.8%. Among the 74 cases studied, 37(46%) cases had an Hb of more than 11 g/dL, 22 cases had mild anemia, 12 cases had moderate anemia, and three cases had severe anemia. Conclusion This study concluded that regular monitoring of the Mentzer index along with HPLC analysis is an effective approach in identifying beta-thalassemia trait cases and further providing genetic counseling among the couples that will help in reducing high-risk pregnancy and the birth of a child with thalassemia major.

Revolutionizing Anemia Classification with Multilayer Extremely Randomized Tree Learning Machine for Unprecedented Accuracy

Anemia is a prevalent global health issue that is characterized by a deficit in red blood cells or low levels of hemoglobin. This condition is influenced by various causes, including nutritional inadequacies, chronic diseases, and genetic predisposition. The incidence of the phenomenon exhibits variation across different geographical regions and demographic groups. This pioneering research investigates the identification and classification of anemia, potentially leading to transformative advancements in the discipline. The classification of anemia encompasses four distinct groups, namely Beta Thalassemia Trait, Iron Deficiency Anemia, Hemoglobin E, and Combination. This comprehensive categorization offers clinicians a more refined and detailed comprehension of the condition. The integration of deep learning and machine learning in the Multilayer Extremely Randomized Tree Learning Machine (MERTLM) model represents a departure from traditional approaches and a significant advancement in the field of medical categorization accuracy. The MERTLM approach integrates randomized tree with multilayer extreme learning machine (M-ELM) representation learning, hence emphasizing the possibility of interdisciplinary collaboration in the field of diagnostics. In addition to its impact on anemia, artificial intelligence (AI) is playing a significant role in revolutionizing medical diagnosis by emphasizing the integration of innovative methods. This study utilizes the combined capabilities of machine learning and deep learning to improve accuracy. Notably, recent developments have resulted in an exceptional accuracy rate of 99.67%, precision of 99.60%, sensitivity of 99.47%, and an amazing F1-Score of 99.53%. This study represents a significant advancement in the field of anemia research, providing valuable insights that may be applied to intricate medical issues and enhancing the quality of patient care.

Red Cell Parameters in Beta Thalassemia Trait; Comparison between Iron Deficient and Non-Deficient Carriers

Objective: To compare hematological parameters in iron-deficient and non-deficient carriers of beta thalassemia trait. Study Design And Setting: Comparative cross-sectional study. This study was conducted at the Department of Hematology at PNS SHIFA Hospital, Karachi for six months (February 2023 to July 2023). Methodology: This comparative cross-sectional study included a total of 304 cases with beta thalassemia trait and was divided into two groups; the Iron-deficient (ID+) and iron-deficient (ID-) group. The study focused on red cell parameters i.e, Hemoglobin (Hb), TRBC, MCV, MCH and RDW. Haemoglobin Electrophoresis results of both groups were also compared. Descriptive statistics were expressed as mean ± SD and the Chi-square test was assigned. A p-value = 0.05 was considered statistically significant. Results: Out of the total 304 subjects, 76 (25.0%) had iron deficiency, and 228 (75.0) had sufficient iron stores. Mean age of patients was 18 (Range: 3 – 35) years. HbA levels were similar in both the groups with p-value &gt; 0.05. While all other parameters compared showed marked differences among the two groups and were found to be statistically significant. Hb, TRBC, MCV MCH showed lower values in the ID+ group while RDW was lower in the ID- group. Conclusion: Red Cell parameters and HBA2 levels in beta thalassemia trait vary significantly among the iron deficient vs non-deficient group. Hence due consideration is needed in screening of beta thalassemia trait in patients with iron deficiency anemia.

Screening of voluntary blood donors for beta-thalassemia trait in an endemic area in Northwest India for 15 years: Results and future directions after screening more than 300 thousand donors

Abstract: BACKGROUND: North-West India has a high prevalence of the Thalassemia, and the Beta Thalassemia Trait often remains undetected in the population. Recognizing the need to address this public health issue, we initiated “Blood the Lifeline” project in 2006 with the aim to eradicate Thalassemia through proactive measures, including screening of voluntary blood donors. AIM: The primary aim of this study was to screen voluntary blood donors in an endemic area in northwestern India for Thalassemia trait. The study aimed to determine its prevalence, identify gender and ethnic group-wise distributions, and assess the implications for future interventions. METHODS: The screening program was conducted from January 2006 till December 2022. Voluntary blood donors were recruited from the target area and underwent Thalassemia trait screening. The screening process involved High Performance Liquid Chromatography using VARIANT II fully automated HPLC system to identify Thalassemia trait. Data regarding the total number of cases screened, gender distribution, ethnic group-wise distribution, and positive and negative cases were collected and analyzed. Screening Process: EDTA Pilot tube from each donor was collected and analyzed within 24 hrs of collection. RBC Counts, Hb Concentration, MCV, MCH, RDW-SD were noted to differentiate between Iron Deficiency Anaemia &amp; thalassemia trait &amp; following Criteria’s were taken into account: Total RBC Count: &gt; 5.0 x 106 / micro-liter, Hb: &lt; 11.7 g/dl, MCV: &lt; 77 fl, MCH: &lt; 28 pg &amp; RDW-SD: &lt; 45 fl. A combination of Formulas like Mentzer’s index= MCV/RBC &lt;13; Shine and Lal Index (S&amp;L) = MCV × (MCH/100) &lt; 1530; Green &amp; King (MCV2) × RDW]/ (Hb × 100) &lt; 65 were used for screening. All the above formulas were introduced into the Blood Bank Software to exclude out the blood units requiring screening &amp; confirmation. If any of the samples were positive on initial screening, then confirmatory test was done by demonstrating the elevation of concentration of HbA2 by HPLC VARIANT II fully automated analyser. RESULTS: A total of 377,503 voluntary blood donors for a 16 year period were screened and data was analysed .The Mean Hemoglobin of positive donors was 12.1 gm/dl; Mean RBC Count was 6.24 m/cu mm, MCV 67.79 fl, MCH 21.04 pg, RDW-SD 42.11fl &amp; HbA2 was 7.48%. The majority of positive cases were found in the Sindhi (16.68%), Punjabi (10.32%), and Muslim (9.81%) ethnic groups. The Rajasthani population accounted for 6.01% of positive cases. CONCLUSION: This comprehensive screening program revealed a relatively high prevalence of Thalassemia trait in 2.29% of the screened population. The communities with higher prevalence (Sindhi, Punjabi, and Muslim) were educated about the disease and a targeted screening program will be further carried out in these ethnic groups. The data helped in planning genetic counseling, carrier screening, and pre-marital screening programs to reduce the transmission of Thalassemia in these populations. By focusing efforts on specific groups and locations with higher prevalence, a community based approach to prevent the birth of children with Thalassemia major is being implemented. It is also being used for analyzing the implications of different local policies pertaining to Thalassemia trait in the region. Collaborative efforts between healthcare organizations, community leaders, and governmental agencies are crucial to address the burden of Thalassemia and work towards its eradication. The results of this study serve as a foundation for future initiatives aimed at minimizing the impact of Thalassemia at a community level.

Moyamoya Syndrome in a Child with Beta-Thalassemia Trait: A Case Report with Review of Literature

Background: The association of moyamoya angiopathy with hematological conditions such as sickle cell anemia and beta-thalassemia major or intermedia is well-known, but moyamoya syndrome (MMS) associated with thalassemia trait is hardly reported. We report such a rare association. Clinical Description: A 7-year-old boy presented with right-sided monoparesis with right-sided focal seizures, along with right-sided upper motor neuron type facial nerve palsy. He had a history of recurrent transient episodes of limb weakness, which were unevaluated. Examination revealed pallor and mild splenomegaly. Management and Outcome: Routine investigations revealed microcytic hypochromic anemia with normal serum iron levels. High-performance liquid chromatography was suggestive of beta-thalassemia trait. Contrast-enhanced computerized tomography of the head showed infarction in the territory of the left anterior cerebral artery (ACA) and middle cerebral artery (MCA). Magnetic resonance angiography revealed significantly attenuated bilateral internal carotid arteries in the supraclinoid region with attenuated bilateral ACA and bilateral MCA along with collateral formation suggestive of moyamoya angiopathy. The final diagnosis of MMS secondary to beta-thalassemia trait was made. The child improved with aspirin and supportive management. Conclusion: MMS can be rarely associated with the beta-thalassemia trait. Such an underlying, unsuspected heterozygous beta-thalassemia (trait) may be diagnosed only after the identification of moyamoya disease following a stroke.

Frequency of anemia in individuals with beta-thalassemia trait.

Objective: To determine the frequency of anemia in carriers of Beta thalassemia Study Design: Retrospective Observational study. Setting: PAEC General Hospital, Islamabad, Pakistan. Period: 1st January 2022 to 30th June 2022. Methods: In this descriptive study, 131 carriers of Beta-thalassemia trait, diagnosed by hemoglobin electrophoresis on cellulose acetate membrane at alkaline pH, of any age and both genders were included. Complete blood counts were performed by hematology analyzer of Sysmex XN-1000 to determine hemoglobin level and red blood cell indices i.e. mean corpuscular volume. The studied parameters included hemoglobin and mean corpuscular volume as quantitative variables. Severity and type of anemia were the qualitative variables of this study and were expressed in terms of frequency and percentages. SPSS 19 version software was used for data analysis. Results: 131 carriers of Beta-thalassemia traits were included in study. 58 (44.27%) were males while 73 (55.73%) were females, male to female ratio being 1: 1.3. Of 131 beta thalassemia traits 67 (51.15%) were found to be anemic while 64 (48.85%) had normal hemoglobin for given age and gender. The mean corpuscular volume of anemic and non-anemics was 59.54+5.82 fl and 63.70+6.95 fl respectively. Mean hemoglobin level of anemic Beta-thalassemia traits was 9.42+1.05 g/dl while non-anemic patients was 12.12+1.39 g/dl. Conclusion: Burden of anemia among carriers of Beta-thalassemia traits is high. Understanding the prevalence of anemia in individuals with the trait is crucial for optimizing healthcare interventions and improving the quality of life for affected individuals.

Spectrum of Hemoglobinopathies in Tertiary Care Hospitals of Rawalpindi and Islamabad

Hemoglobinopathies, including Thalassemia and sickle-cell syndromes are lifelong diseases with a significant impact on patients, families, and healthcare resources. Despite therapeutic progress, Pakistan, located within the Thalassemia belt, lacks comprehensive data on the epidemiology, clinical course, mortality, complications, and treatment outcomes of Thalassemia. Objective: To determine the frequency of haemoglobinopathies in Tertiary Care Hospital of Rawalpindi and Islamabad. Methods: A retrospective cross-sectional study of 7 months was conducted on the local population of Islamabad and Rawalpindi from January 2020 to July 2020. Total 600 patients referred for Hb electrophoresis were initially selected for study. Data from 300 patients were collected from PIMS Hospital, Islamabad, and 300 from Holy Family Hospital, Rawalpindi. Clinical information for each patient was recorded separately, data were statistically analyzed using Microsoft Excel version 2016 and graphs were made on GraphPad Prism version 08. Results: Out of 600 patients from Rawalpindi and Islamabad 227 (37.84%) patients were found to have hemoglobinopathies. Beta Thalassemia trait was the most common disorder among those with hemoglobinopathies (47.13%), followed by beta Thalassemia major (23.34%), sickle Beta Thalassemia (10.57%), sickle cell disease (6.6%), Hb D trait (5.28%), Hb D/beta Thalassemia (3.96%), Hb E trait (2.2%), and sickle cell trait (0.88%). Conclusions: The study showed a significantly high frequency of hemoglobinopathies in the capital city Islamabad and Rawalpindi. β- Thalassemia trait and β- Thalassemia major were found in high frequency among various hemoglobin disorders.