Thalassemia Syndromes Research Articles

THE PREVALENCE OF THE THALASSEMIA TRAIT AMONG THE EAST MALAYSIAN STUDENTS IN THE FACULTY OF HEALTH SCIENCES, UNIVERSITI TEKNOLOGI MARA, UiTM SELANGOR

The thalassemia trait is an asymptomatic thalassemia syndrome that increases the risk of developing a more severe condition. This study aimed to determine the prevalence of the thalassemia trait among Sabah and Sarawak students enrolled in the Faculty of Health Sciences at Universiti Teknologi MARA, UiTM Selangor. The study was carried out over 3 months following approval from the ethics and research committees of Universiti Teknologi MARA, UiTM Shah Alam. A universal sampling method was used where the blood samples were collected from the 40 students, 16 from Sabah and 24 from Sarawak, of various ethnicities. All subjects were asked to fill out consent forms. A volunteer medical laboratory staff member assisted in taking whole blood samples from the subjects’ venous blood. The blood was then collected in a 3 mL EDTA (ethylenediaminetetraacetic acid) tube and was tested for thalassemia using a Full Blood Count (FBC) and a Full Blood Picture (FBP), as well as a Mentzer Index (MI) calculation, gel electrophoresis, and an H-inclusion test. In conclusion, the prevalence of the thalassemia trait is 7.5% (3) out of 40 volunteers among students from Sabah and Sarawak in the Faculty of Health Sciences at UiTM Selangor.

Anemia in an ethnic minority group in lower northern Thailand: A community-based study investigating the prevalence in relation to inherited hemoglobin disorders and iron deficiency.

Anemia is a globally well-known major public health problem. In Southeast Asia where there is ethnic diversity, both iron deficiency (ID) and inherited hemoglobin disorders (IHDs) are prevalent and are considered to be the major factors contributing to anemia. However, little is known about the anemia burden among the ethnic minorities. In this study, we determine the burden of anemia, in relation to ID and IHDs, among the Karen ethnic minorities living in the rural area of lower northern Thailand. A cross-sectional community-based study was conducted at Ban Rai district, Uthai Thani province. Study participants included 337 Karen people aged over 18 years. Socio-economic and health-related information were obtained through interviews and recorded by local health staff. Anemia, IHDs and ID were diagnosed according to standard laboratory methods. Multivariate logistic regression analysis was applied to identify risk factors of moderate-to-severe anemia. The prevalence of overall anemia was 27.9% (95% CI = 23.2-33.0). Mild and moderate anemia were detected in 18.7% (95% CI = 14.7-23.3) and 8.9% (95% CI = 6.1-12.5) respectively. Severe anemia was found in one case (0.3%). Various forms of IHDs were identified in 166 participants, constituting 49.3% (95% CI = 43.8-54.7). The most common form of IHDs was α+-thalassemia (32.9%), followed by β-thalassemia (12.2%), α0-thalassemia (4.2%), hemoglobin E (3.9%), and hemoglobin Constant Spring (0.9%). Among 308 participants who were investigated for ID, the prevalence was discovered to be 6.8% (95% CI = 4.3-10.2). Analysis of risk factors of moderate-to-severe anemia revealed that individuals with ID, β-thalassemia and age > 65 years were at high risk with adjusted odds ratio of 17 (95% CI = 3.8-75.2), 6.2 (95% CI = 1.4-27.8) and 8.1 (95% CI = 1.6-40.4) respectively. Anemia among the Karen is of public health significance; and IHDs are the major contributing factors. Because of the high risk of developing moderate-to-severe anemia, special attention should be paid to individuals affected with ID, β-thalassemia and the elderly. Public awareness of the health burden of severe thalassemia syndromes should also be campaigned.

Prospective screening for δ-hemoglobinopathies associated with decreased hemoglobin A2 levels or hemoglobin A2 variants: A single center experience

Backgroundδ-hemoglobinopathies may lead to misdiagnosis of several thalassemia syndromes especially β-thalassaemia carrier, it is important to evaluate the δ-globin gene defects in areas with high prevalence of globin gene disorders. We describe a prospective screening for δ-hemoglobinopathies in a routine setting in Thailand. MethodsStudy was done on a cohort of 8,471 subjects referred for thalassemia screening, 317 (3.7%) were suspected of having δ-globin gene defects due to reduced hemoglobin (Hb) A2 levels and/or appearance of Hb A2-variants on hemoglobin analysis. Hematologic and DNA analysis by PCR and related assays were carried out. ResultsDNA analysis of δ-globin gene identified seven different δ-globin mutations in 24 of 317 subjects (7.6%). Both known mutations; δ−77(T>C) (n = 3), δ−68(C>T) (n = 1), δ−44(G>A) (n = 8), Hb A2-Melbourne (n = 5), δIVSII−897(A>C) (n = 5), and Hb A2-Troodos (n = 1) and a novel mutation; the Hb A2-Roi-Et (n = 1) were identified. This Hb A2-Roi-Et, results from a double mutations in-cis, δCD82(AAG>AAT) and δCD133(GTG>ATG), was interestingly found in combination with an in trans, 12.6 kb deletional δβ0-thalassemia in an adult Thai woman who had no Hb A2 and elevated Hb F. A multiplex-allele-specific PCR was developed to detect these novel δ-globin gene defects. ConclusionsThe result confirms a diverse heterogeneity of δ-hemoglobinopathies in Thailand which should prove useful in a prevention and control program of thalassemia in the region.

Incidence of impaired glucose tolerance and diabetes mellitus in transfusion dependent thalassemia patients of rural Bengal - An institutional study

: Thalassemia is the world’s commonest monogenic disorder. Molecular biology and genetics have revealed more than 200 mutations of thalassemia syndrome. These children become symptomatic from progressive haemolytic anaemia. They have to take lifelong treatments with regular packed red blood cell transfusion. Our body has no effective means of iron excretion and this leads to progressive iron accumulation in various organs after prolonged blood transfusion. This results in dysfunction of liver, heart and endocrine system and increased mortality. Iron toxicity to pancreatic beta cell leads to impairment in glucose metabolism. : Our study aims to find out the incidence of impaired glucose tolerance (IGT) and diabetes mellitus (DM) in transfusion dependent thalassemia major patients. This is an observational descriptive study carried out from January 2017 to June 2018. The study included 48 samples. There post-prandial blood sugar level and glycated haemoglobin (HbA1c) was analysed. Any proved case of juvenile diabetes mellitus was excluded from the study. We found that the incidence of IGT and DM were 12.5% and 4.16% respectively in our study population. The blood sugar level was significantly high in study group (p=<0.0001) as compared to the control group. The present study showed strong correlation between units of blood transfusion and blood sugar level as well as HbA1C percentage (in both cases p= <0.00001.)Thalassemia patients receiving regular blood transfusion are at increased risk of developing IGT and DM. Early initiation of chelation and judicious use of blood transfusion must be considered for these patients to prevent such complications.

5612976 FIRST ADMINISTRATION OF HYPOXIC BLOOD IN A TRANSFUSION-DEPENDENT PATIENT

Background: Many patients with inherited and acquired anemias such as sickle cell disease, thalassemia and myelodysplastic syndromes (MDS) are transfusion-dependent, requiring regularly scheduled red blood cell (RBC) transfusions.1 Chronic transfusions are associated with a range of complications, such as transfusion-related adverse events (AEs) and iron overload.1 Frequent transfusions may also have a negative impact on patient quality of life (QoL)1 and access is often difficult. To reduce transfusion burden in dependent patients, Hemanext Inc. (Lexington, MA, United States) has developed a CE mark certified device to process and store red blood cells hypoxically - CPD/PAGGSM leukocytes-reduced (LR), O2/CO2 reduced.2 By reducing oxidative stress, hypoxic blood storage has been shown to improve the quality and function of RBCs,3 demonstrating that lower volumes of hypoxic RBCs are required to resuscitate from hemorrhagic shock and maintain hemodynamics than conventional RBCs in animal models.4 This may have several benefits in transfusion-dependent patients, including increasing the interval between transfusions and hence potential to reduce iron overload. Aims/Methods: A pilot clinical study in Norway is investigating the safety of a single administration of hypoxic RBCs in patients with hematologic malignancies and patients with burns. The primary outcome of the study is the occurrence of AEs at Day 7±1 post-transfusion. Secondary outcomes include assessment of AEs from enrollment to subsequent RBC transfusion (or Day 28) and the evolution of hemoglobin (Hb) levels pre- and post-transfusion. For the subset of patients with hematologic malignancies, the transfusion trigger is set to Hb <9.0 g/dL, and two units of hypoxic RBCs are administered. Results: In August 2022, following his informed consent, the first patient was transfused with hypoxic RBCs; this patient was also the first to receive hypoxic blood within Hemanext’s overall clinical program. The patient was an 80-year-old man who initially presented with anemia and diagnostic workup revealed bone marrow smear with morphological features of erythroid dysplasia with ring sideroblasts in 30% of cells and mutation in the SF3B1 gene. After initial response to treatment, he became transfusion-dependent, and has received 2 RBC units every 2 weeks for a year. The patient had a pre-transfusion Hb level of 8.1 g/dL and received 2 units of O+ hypoxic RBCs over 2 hours without any complications. No adverse events were recorded on Day 1 and the patient experienced no adverse events by Day 7. Further outcomes will be reported. Conclusion: Hypoxic RBCs processed with the CPD/PAGGSM LR, O2/CO2 reduced system were well tolerated in this patient; Hb level was within the target range at follow-up, supporting that hypoxically stored RBCs function appropriately. The study is ongoing and will continue to assess hypoxic RBCs in patients with hematologic malignancies and patients with burns. Enrolment within the wider clinical program – including studies investigating hypoxic RBC administration in patients with thalassemia in Italy and sickle cell disease in the US – is planned.

Myocardial infarction in patients with severe beta thalassaemia: a case series

BackgroundCardiac disease remains a dominant if not the most important cause of morbidity and mortality in patients with thalassaemia, particularly in those with thalassaemia major. Myocardial infarction and coronary artery disease however are rarely reported.Case presentationsThree older patients with three distinct thalassaemia syndromes presented with acute coronary syndrome. Two were heavily transfused whilst the other was a minimally transfused patient. Both heavily transfused patients had ST-elevation myocardial infarctions (STEMI) while the minimally transfused patient had unstable angina. Coronary angiogram (CA) was normal in two patients. One patient who developed a STEMI had a 50% plaque. All three were managed as standard ACS, although the aetiology appeared non-atherogenic.ConclusionsThe exact etiology of the presentation, remains a mystery and therefore the rational use of thrombolytic therapy, carrying out angiogram in the primary setting, using and continuing antiplatelet and high dose statins all remains unclear in this sub group of patients.

An evaluation of deferiprone as twice-a-day tablets or in combination therapy for the treatment of transfusional iron overload in thalassemia syndromes

ABSTRACT Introduction Regular blood transfusions in patients with thalassemia syndromes can cause iron overload resulting in complications including cirrhosis, heart problems, or endocrine abnormalities. To prevent iron overload toxicity in these patients, three iron chelators are currently FDA-approved for use: deferoxamine, deferasirox, and deferiprone. In the United States, deferiprone has been approved for three times daily dosing since 2011 and has recently gained approval for twice-daily administration. Areas Covered A PubMed literature search was performed with the keywords ‘deferiprone’ and ‘thalassemia.’ Relevant original research studying deferiprone’s effects on transfusional iron overload in patients with thalassemia syndromes was included. Exclusion criteria included case reports and review papers. Deferiprone is effective at reducing serum ferritin levels in patients with iron overload. Twice-daily administration provides a similar level of iron chelation as three times daily dosing with a comparable side effect profile and increased patient acceptability. Expert Opinion New studies are highlighting deferiprone’s potential for combination therapy with either deferoxamine or deferasirox to improve iron chelation. Deferiprone’s ability to significantly decrease cardiac and liver iron content can be utilized in other transfusion-dependent hematologic conditions, as evidenced by its recent approval for use in the United States for sickle cell disease or other anemias.

Hemorheological profiles and chronic inflammation markers in transfusion-dependent and non-transfusion- dependent thalassemia.

The rheological properties of blood play an important role in regulating blood flow in micro and macro circulation. In thalassemia syndromes red blood cells exhibit altered hemodynamic properties that facilitate microcirculatory diseases: increased aggregation and reduced deformability, as well as a marked increase in adherence to the vascular endothelial cells. A personalized approach to treating thalassemia patients (transfusions, iron chelation, and splenectomy), has increased patients' life expectancy, however they generally present many complications and several studies have demonstrated the presence of high incidence of thromboembolic events. In this study the hemorheological profiles of thalassemia patients have been characterized to point out new indices of vascular impairment in thalassemia. Plasma viscosity, blood viscosities at low and high shear rates (η1 and η200, respectively), erythrocyte aggregation index (η1/η200), and the erythrocyte viscoelastic profile (elastic modulus G', and viscous modulus G") have been studied in transfusion-dependent and non-transfusion-dependent thalassemia patients. Moreover, the levels of inflammation biomarkers in thalassemia have been evaluated to investigate a relationship between the biomarkers, the disease severity and the rheological parameters. The biomarkers studied are the main components of the immune and endothelial systems or are related to vascular inflammation: cytokines (IL-2, IL-6, IL-10, IL-17A, TNF-alpha), chemokines (IL-8, MIP-1alpha), adipocytokines (leptin and adiponectin), growth factors (VEGF, angiopoietin-1), adhesion molecules (ICAM-1, VCAM-1, E-selectin, L-selectin), and a monocyte/macrophage activation marker (CD163). This study shows that transfusion-dependent thalassemia patients, both major and intermedia, have blood viscosities comparable to those of healthy subjects. Non-transfusion-dependent thalassemia intermedia patients show high blood viscosities at low shear rates (η1), corresponding to the flow conditions of the microcirculation, an increase in erythrocyte aggregation, and high values of the elastic G' and viscous G" modules that reflect a reduced erythrocyte deformability and an increase in blood viscosity. Levels of cytokines, chemokines and adhesion molecules are different in transfusion- and non-transfusion dependent patients and positive correlations between η1 or η1/η200 and the cytokines IL-6 and IL-10 have been observed. The evaluation of the hemorheological profiles in thalassemia can provide new indicators of vascular impairment and disease severity in thalassemia in order to prevent the onset of thromboembolic events.

Thalassemia Screening by Sentiment Analysis on Social Media Platform Twitter

Thalassemia syndrome is a genetic blood disorder induced by the reduction of normal hemoglobin production, resulting in a drop in the size of red blood cells. In severe forms, it can lead to death. This genetic disorder has posed a major burden on public health wherein patients with severe thalassemia need periodic therapy of iron chelation and blood transfusion for survival. Therefore, controlling thalassemia is extremely important and is made by promoting screening to the general population, particularly among thalassemia carriers. Today Twitter is one of the most influential social media platforms for sharing opinions and discussing different topics like people’s health conditions and major public health affairs. Exploring individuals’ sentiments in these tweets helps the research centers to formulate strategies to promote thalassemia screening to the public. An effective Lexiconbased approach has been introduced in this study by highlighting a classifier called valence aware dictionary for sentiment reasoning (VADER). In this study applied twitter intelligence tool (TWINT), Natural Language Toolkit (NLTK), and VADER constitute the three main tools. VADER represents a gold-standard sentiment lexicon, which is basically tailored to attitudes that are communicated by using social media. The contribution of this study is to introduce an effective Lexicon-based approach by highlighting a classifier called VADER to analyze the sentiment of the general population, particularly among thalassemia carriers on the social media platform Twitter. In this study, the results showed that the proposed approach achieved 0.829, 0.816, and 0.818 regarding precision, recall, together with F-score, respectively. The tweets were crawled using the search keywords, “thalassemia screening,” thalassemia test, “and thalassemia diagnosis”. Finally, results showed that India and Pakistan ranked the highest in mentions in tweets by the public’s conversations on thalassemia screening with 181 and 164 tweets, respectively.

Undiagnosed Dual Blood Disorder – Thalassemia with Acute Myeloid Leukemia

Thalassemia syndromes represent a group of inherited disorders characterized by decreased synthesis of one or more of the four globin chains in hemoglobin. The clinical spectrum ranges from asymptomatic carrier state to transfusion-dependent severe disease. The availability of better treatment options has increased the life expectancy in these patients and consequently paved the way to develop malignancies. Although many studies are published on the association of solid organ and lymphoid malignancies, only one case has been reported so far for acute myeloid leukemia (AML) coexisting with thalassemia syndromes. Herein, we report the first case of AML associated with beta-thalassemia in an adult Indian expatriate woman in Qatar. She presented with prolonged bleeding after a dental procedure. She was diagnosed as concurrent AML and beta-thalassemia trait on the laboratory evaluation. This case signifies the use of peripheral blood film evaluation for any abnormal hemograms in the modern era of automation. It also warrants caution for clinicians in suspecting malignancies in thalassemia although direct genetic linkage or associated risk is a matter of research.

Elective Splenectomy for Haemolytic Anaemia: A Case Series

The spleen plays an important role in immune surveillance and haematopoiesis. Elective splenectomy is sometimes indicated for excessive cellular destruction (hypersplenism) or sequestration, lymphomatous or myeloid disease, or tumours. Hereditary haemolytic anaemias are disorders with a variety of causes, including red cell membrane defects, red blood cell enzyme disorders, congenital dyserythropoietic anaemias, thalassaemia syndromes, and haemoglobinopathies. Splenectomy is one of the therapeutic approaches in the management of haematological conditions. This is case series of 12 cases who underwent elective splenectomies for haemolytic anaemias in a tertiary care centre, over a period of one year. Out of the 12 patients, 10 patients were diagnosed to have Hereditary Spherocytosis (HS) and 2 patients were diagnosed with sickle cell anaemia. For all patients, preoperative blood transfusion was done to bring the Haemoglobin (Hb) above 9 g/dL for elective splenectomy. Among the 10 patients with HS, 6 patients had concomitant cholelithiasis for which cholecystectomy was done in the same sitting and three patients developed postoperative complication which was managed appropriately with no mortality and minimum morbidity. However, more detailed studies on this subset of patients are needed for the establishment of guidelines and optimal outcomes.

Estimating the Incidence Frequency of Helicobacter pylori Co-infection with Hepatitis C Virus among Thalassemia Individual in Wasit Governorate of Iraq

Objective(s): Helicobacter pylori (H. pylori) is a gram-negative bacterium that plays a significant role in developing gastrointestinal diseases such as peptic ulcers. H. pylori infection affects more than half of the world’s population. This pathogen incidence becomes more effective among thalassemia patients, a common genetic disorder characterized by a point mutation that leads to impaired production of the β-globin chain. Chronic hepatitis C is a chronic disease caused by the hepatitis C virus (HCV) that has significantly increased morbidity and mortality rates in these patients due to liver failure or hepatocellular carcinoma. Methods: Current study included 90 β-thalassemia patients admitted to the thalassemia hematology center in Al-Kut women and children Hospital, Wasit province, Iraq from September 2020 to November 2021. The patients are divided into two groups (β-thalassemia with HCV group and β-thalassemia without HCV). First and second groups contain 32 and 58 specimens of blood and stool samples, respectively. The patient diagnosed with thalassemia syndrome regularly attended the thalassemia hematology center for transfusion and chelation and follow up on Hb level and iron status. This study aimed at serological and molecular diagnosis of co-infection H. pylori with Hepatitis C virus (HCV) among thalassemia patients and diagnosis infection rate. Diagnosis was used Serological enzyme-linked immunoassay (ELISA) techniques for HP-IgG, Level of ferritin, liver function test will be determined and Nested PCR method targeting the molecular diagnosis will be used to confirm H. pylori 23S rRNA using DNA extracted from stool samples. Results: 90 β-thalassemia patients sample were diagnosed by Serological ELISA techniques for HP-IgG and the result showed 30 samples were positive (18 from the β-thalassemia with HCV group and 12 from the β-thalassemia without HCV)and 60 samples negative for HP-IgG and Nested polymerase chain reaction (PCR) method targeting the molecular diagnosis will be used to confirm H. pylori 23S rRNA using DNA extracted from stool for 30 stool samples revealed 13 samples positive (9 from the β-thalassemia with HCV and 4 from β-thalassemia without HCV) while 17 samples were negative. Conclusions: The predominance of H. pylori among patients in Wasit was 43.3%. Levels of ferritin have significant correlation with H. pylori in HCV patients. There was a positive correlation between hepatitis C status and high H. pylori rate when compared with β-thalassemia without HCV. Splenoctomy was a positive correlation with H. pylori in β-thalassemia with HCV. Moreover, these results recommend study about the virulence factor and genes. Other molecular studies are needed for detecting more virulence genes in H. pylori bacteria such as real-time PCR and sequencing of H. pylori in patients with thalassemia, especially those with high serum ferritin.

STUDY OF SPECTRUM OF HEMOGLOBINOPATHIES IN ADULT AGE GROUP DIAGNOSED ON HIGH PERFORMANCE LIQUID CHROMATOGRAPHY IN TERTIARY CARE HOSPITAL

Background: Inherited abnormalities of hemoglobin synthesis (hemoglobinopathies) include a myriad of disorders ranging from thalassemia syndromes to structurally abnormal hemoglobin variants. Aims and Objectives: To study spectrum of hemoglobinopathies in adult age group diagnosed on HPLC in tertiary care hospital. Materials and Methods: The present study carried out in the deparment of pathology , DR PDMMC AMRAVATI over a period of 18 months from january 2021 to june 2022. A total of 800 cases were included in the present study. The age group of patients ranged from 19 years and above. HPLC , complete blood count, and peripheral smear examination were done in all the cases. Results and Discussion: In the present study total 800 patients were included out of which 134 cases displayed abnormal hemoglobin fractions on HPLC. It was seen that majority of the patients in study were in the 19yrs to 30yrs. The most common hemoglobinopathy observed in the present study was sickle cell trait (51.50 %) followed by Beta Thalassemia trait (26.12 %) and Sickle cell disease (16.42 %).HbDpunjab trait was observed in 3.74 % cases. Sickle cell Disease + Beta thalassemia trait ,HbE trait, HbE homozygous were observed in 0.74% cases each. Conclusion: Detection of β-thalassemia carriers and other structural variants will provide a preliminary insight to the prevalence of hemoglobinopathies in hospital based patients.Awareness can be created in an effort to prevent the birth of affected children.The present study is intended to contribute to the available data as the identification of these disorders is important epidemiologically and aids in prevention of more serious hemoglobin disorders.

Evaluation of immune system in patients with transfusion-dependentbeta-thalassemia in Rasoul-e-Akram Hospital in 2021: A descriptive cross-sectional study.

Background and aimsThalassemia syndromes are the most common hemoglobinopathy globally related to blood transfusion and iron overload in the body. Splenectomy, excessive iron overload, and repeated exposure to antigens in blood transfusions can cause severe damage to the patient's immune system making the patient prone to frequent infection. This study evaluates the immune system status and infection rate in beta‐thalassemia major patients receiving iron chelators.MethodsThis descriptive cross‐sectional study was performed in Rasoul‐e‐Akram Hospital on patients with a beta‐thalassemia major who had iron overload due to frequent blood transfusions. The percentage of lymphocyte markers was determined by flow cytometry. Serum levels of immunoglobin were measured by nephelometric assay. Also, Nitro blue tetrazolium and dihydrorhodamine assays were used to evaluate the phagocytic function.ResultsOf the 106 patients participating in this study, 59 (55.7%) and 47 (44.3%) are male and female, respectively. The mean age ± SD of participants was 24.7 ± 12.1 years with 4 to 55 years. There was no significant correlation between sex, the C3 and C4 complements, the lymphocyte markers, and the immunoglobulin levels. Furthermore, all of these variables increased significantly over 30 (p < 0.05). Moreover, there was a strong positive correlation between splenectomy and IgG immunoglobulin (p < 0.001) and CD16 (p = 0.005) lymphocyte marker.ConclusionIron chelator agents effectively improve patients' immune system with thalassemia major. The increase in IgG and IgM immunoglobulins levels is due to frequent blood transfusions, which stimulate the immune system.

A prospective study on prevalence of thalassemic gene disorder and hemoglobinopathies in pregnancy: Antenatal and intranatal outcome in a hospital-based population of Eastern India

Background: Thalassemia syndromes are autosomal recessive disorders and the most commonly inherited hemoglobinopathies in the world. Among these, β-thalassemia is the most common type of thalassemia in Eastern India and in West Bengal. Thalassemic mothers are more predisposed to maternal complications such as hypertensive disorders, gestational diabetes mellitus (GDM), and adverse neonatal outcome in terms of low birth weight, prematurity, etc. This study was to assess the effect of thalassemia gene disorder and hemoglobinopathies (thal-hbpathy) on fetomaternal health. Aims and Objectives: This study was done to evaluate the effect of thal-hbpathy on fetomaternal health and to compare their antenatal, intranatal outcome with control unaffected mothers, and with anaemic non-thalassemic mothers. Materials and Methods: This is a prospective and observational study of 150 women who attended tertiary care hospital during 18 months, fulfilling pre-defined inclusion and exclusion criteria. All women were evaluated during antenatal and intranatal period. Observations were recorded and interpreted. Results: Among 150 participants, 80(53.3%) were having normal hemoglobin (Hb) level and normal hemoglobin high performance liquid chromatography(Hb-HPLC), 54(36.7%) had anemia (Hb &lt;10.9g/dl) with normal Hb pattern on HPLC, and 16(10.66%) had thal-hbpathy. Hb-HPLC revealed β-thalassemia trait in 7.3%, E β-thalassemia trait in 0.7%, whereas HbE heterozygous 2.7% in our study population. Majority (15/16) of thal-hbpathy patients were anemic. Oligo-hydramnios was detected in 18.7% of thalassemic women as compared to anemic (3.7%) and normal group (3.7%), which were significant. Obstetric cholestasis (OC) 12.5%(2/16) and intrauterine growth restriction (IUGR) were observed in thal-hbpathy group antenatal patients which were statistically significant P&lt;0.05. Conclusion: Overall prevalence of thalassemia was 10.7%. The important fetomaternal complications observed were prematurity, IUGR, OC, oligohydramnios, OC(PIH), and GDM.

In Vitro Study of Ineffective Erythropoiesis in Thalassemia: Diverse Intrinsic Pathophysiological Features of Erythroid Cells Derived from Various Thalassemia Syndromes.

Defective hemoglobin production and ineffective erythropoiesis contribute to the pathophysiology of thalassemia syndromes. Previous studies in the field of erythropoiesis mainly focused on the severe forms of thalassemia, such as β-thalassemia major, while mechanisms underlying the pathogenesis of other thalassemia syndromes remain largely unexplored. The current study aimed to investigate the intrinsic pathophysiological properties of erythroid cells derived from the most common forms of thalassemia diseases, including α-thalassemia (hemoglobin H and hemoglobin H-Constant Spring diseases) and β-thalassemia (homozygous β0-thalassemia and β0-thalassemia/hemoglobin E diseases), under an identical in vitro erythroid culture system. Cell proliferation capacity, differentiation velocity, cell death, as well as globin synthesis and the expression levels of erythropoiesis modifying factors were determined. Accelerated expansion was found in erythroblast cells derived from all types of thalassemia, with the highest degree in β0-thalassemia/hemoglobin E. Likewise, all types of thalassemia showed limited erythroid cell differentiation, but each of them manifested varying degrees of erythroid maturation arrest corresponding with the clinical severity. Robust induction of HSP70 transcripts, an erythroid maturation-related factor, was found in both α- and β-thalassemia erythroid cells. Increased cell death was distinctly present only in homozygous β0-thalassemia erythroblasts and associated with the up-regulation of pro-apoptotic (Caspase 9, BAD, and MTCH1) genes and down-regulation of the anti-apoptotic BCL-XL gene.

Common Single Nucleotide Polymorphism of TMPRSS6, an Iron Regulation Gene, Associated with Variable Red Blood Cell Indices in Deletional α-Globin Genotypes.

Red blood cell (RBC) indices, including mean corpuscular volume (MCV) and mean corpuscular haemoglobin (MCH), have been widely used for primary screening for thalassaemia (thal) syndromes. Recently, a single nucleotide polymorphism (SNP) rs855791 of TMPRSS6, an iron regulation gene involved in the substitution of a nucleotide between thymine (T) and cytosine (C) in exon 17 resulted in an amino acid change, p.Val736Ala (V736A), has been described to associate with RBC indices. The objective was to study the effects of common SNP V736A on RBC indices in deletional α-thal variations. SNP rs855791 genotypes were identified from 433 Thai volunteers, including 32.6% males and 67.4% females with an average age of 23.0 ± 8.7 years. These populations included individuals (82.4%) who had normal globin genotype (αα/αα, ββ) and α-thal carriers, which were divided into two subgroups, including α+-thal (-α/αα) (14.1%) and αo-thal (--/αα) (3.5%). Among three SNP genotypes, the C allele gradually expressed higher MCV and MCH than those of the T allele in both α+- and αo-thal traits. Importantly, SNP rs855791 of TMPRSS6 responded to α-globin deletions for sustaining RBC sizes and haemoglobinisation in α-thal carriers.

Prognostic Potential of RDW in Discriminating Hemoglobinopathies among Patients reporting to Aga Khan Hospital, Kisumu

BackgroundRed cell distribution width (RDW) measures the extent of variation in red blood cell (RBC) volume in terms of coefficient of variation. It reflects the degree of variation in RBC’s sizes and shapes, characteristic of iron deficiency and anemias involving RBC destruction, especially hemoglobinopathies. Its values are often available as one of the RBC indices generated as complete blood cell count (CBC) using automated hematology analyzers. Hemoglobinopathies are highly prevalent in malaria-endemic geographical settings like the Sub-Saharan African which has over 200,000 currently documented annual major hemoglobinopathies with an alarming mortality rate of 50–90% by the age of 5 years usually undiagnosed. With a vast growing majority of hemoglobinopathy carriers, this public health problem is projected to escalate by the year 2050 due to unaffordable laboratory tests for screening of newborns and populations as recommended by World Health Organization in resource-limited settings. Therefore, innovative of a cost-effective diagnostic method would improve the survival of these children. The current study aimed to evaluate the overall ability of RDW in discriminating hemoglobinopathy and hemoglobinopathy-free cases within the Lake Victoria Economic Block region of Western Kenya served partly by the Aga Khan Hospital, Kisumu.ObjectiveTo determine the significance of RDW as a tool to differentiate between individuals with hemoglobinopathies and those without.MethodThis was a cross-sectional retrospective comparative hospital-based study that analyzed data from the hematology laboratory database for patients examined using high-performance liquid chromatography during the years 2015–2020. The study consisted of 488 participants (49.4%, n = 241 control; 50.6% n = 247 case, p = 0.786) aged between 1 month and 66 years selected conveniently through census. The relationship between RDW of the controls and cases was analyzed using Mann–Whitney U, Kruskal–Wallis tests among population groups and Dunn’s post hoc test within groups since the data were non-normally distributed.ResultsThe RDW cutoff value was computed at 95% confidence interval (CI), and values greater than this indicated a diagnosis of hemoglobinopathy.ConclusionRDW at 95% CI was 19.9 [14.5 + (2.7 × 2 = 19.9)] cutoff point which proved to be an excellent screening tool for sickle cell disease phenotypes in Western Kenya but would generate many false positive and false negatives for pure Hb AS. RDW is a poor screening tool for, Hb AS + HbF, Hb AS + β thal and β-thalassemia since it could not differentiate diseased from non-diseases populations. Even though RDW proved to be a poor screening tool for beta thalassemia, other complete blood count (CBC) parameters such as MCV and red cell count can be used to identify thalassemia syndromes as well as iron deficiency anemia. Though out of the scope of this work, highlighting the significance of these parameters in addition to the RDW would improve its feasibility as a screening tool for all hemoglobinopathies. Normal reference range for children ≤ 5 years needs to be developed using prospective data for precise marking of disorders associated with red cell anisocytosis, and individuals ≥ 6 years can share RDW normal reference range regardless of their gender.

Chronic anemia: The effects on the connectivity of white matter.

Chronic anemia is commonly observed in patients with hemoglobinopathies, mainly represented by disorders of altered hemoglobin (Hb) structure (sickle cell disease, SCD) and impaired Hb synthesis (e.g. thalassemia syndromes, non-SCD anemia). Both hemoglobinopathies have been associated with white matter (WM) alterations. Novel structural MRI research in our laboratory demonstrated that WM volume was diffusely lower in deep, watershed areas proportional to anemia severity. Furthermore, diffusion tensor imaging analysis has provided evidence that WM microstructure is disrupted proportionally to Hb level and oxygen saturation. SCD patients have been widely studied and demonstrate lower fractional anisotropy (FA) in the corticospinal tract and cerebellum across the internal capsule and corpus callosum. In the present study, we compared 19 SCD and 15 non-SCD anemia patients with a wide range of Hb values allowing the characterization of the effects of chronic anemia in isolation of sickle Hb. We performed a tensor analysis to quantify FA changes in WM connectivity in chronic anemic patients. We calculated the volumetric mean of FA along the pathway of tracks connecting two regions of interest defined by BrainSuite's BCI-DNI atlas. In general, we found lower FA values in anemic patients; indicating the loss of coherence in the main diffusion direction that potentially indicates WM injury. We saw a positive correlation between FA and hemoglobin in these same regions, suggesting that decreased WM microstructural integrity FA is highly driven by chronic hypoxia. The only connection that did not follow this pattern was the connectivity within the left middle-inferior temporal gyrus. Interestingly, more reductions in FA were observed in non-SCD patients (mainly along with intrahemispheric WM bundles and watershed areas) than the SCD patients (mainly interhemispheric).

The spectrum of thalassemia syndromes and abnormal haemoglobins in adult patients based on HPLC in a tertiary care centre of Punjab, India

In the present study adult patients with anemia were analysed for thalassemia syndromes and other haemoglobino pathies by using high performance liquid chromatography. A total of 102 Patients’ blood samples were evaluated for complete blood count, RBC indices, reticulocyte count and peripheral blood film for morphology. For the confirmation and characterization of hemoglobinopathy, ‘BIORAD VARIANT II’ of HPLC instrument with CDM software was utilized. 60.8% of the patients were females while the remaining 39.2% were males. The results of this study showed that 79.4% of patients were having a normal hemoglobin while 17% patients showed the prevalence of thalassemia trait. Two cases of hereditary persistence of fetal hemoglobin (HPFH) were seen and one case each of sickle cell-beta thalassemia (HbSThal) and hemoglobin D-Iran (HD-Iran) were seen. It was observed that 65.4% of the patients without thalassemia trait had normocytic normochromic type of anemia. In contrast, all the patients with thalassemia trait and HbSThal had microcytic hypochromic anemia. This association was statistically significant with hemoglobinopathies mostly having microcytic hypochromic. The present findings show high performance liquid chromatography forms a rapid, accurate, and reproducible tool for the early detection and management of hemoglobinopathies and variants.