Thalassemia Research Articles

Molecular pathways and gene networks in fetal hemoglobin as a novel protein target for beta-thalassemia

Abstract Background: Beta thalassemia is a condition in which the body cannot produce the beta subunit of hemoglobin due to harmful mutations in the globin gene that cause inadequate development of adult hemoglobin (HbA). In beta-thalassemic individuals, fetal hemoglobin (HbF), consisting of two and two subunits, is a potential replacement for HbA with significant therapeutic importance. HbF increase is a powerful and essential therapeutic tool to overcome the problem of beta-thalassemia. Materials and Methods: The GEO2R statistical tool and the GSE96060 dataset from the gene expression omnibus database were used to determine the differentially expressed genes (DEGs). The search tool for the retrieval of interacting genes program was used to reveal connections between these DEGs in samples, followed by applying the molecular complex detection algorithm to identify clusters of genes within these interaction networks. Using ClueGo and CluePedia, the discovered DEGs were subjected to functional annotation, including gene ontology (GO) and enriched molecular pathway analysis. Results: We searched the top 200 DEGs that met the criteria for significance (P-value 0.05; fold two change >1 or 1). Myeloid cell differentiation, erythrocyte differentiation, cellular detoxification, and heme binding are only a few examples of the biological processes and molecular pathways the GO analysis of DEGs identified as having significant alterations. The link between the DEGs in heme biosynthesis and transcriptional dysregulation in cancer was discovered by studying enriched Kyoto encyclopedia of genes and genomes pathways. To find possible targets for beta thalassemia treatments, we looked for the genes Krüppel-like factors 1 (KLF1) and mouse double minute 2 (MDM2). By activating both beta-globin and HbF gamma-globin genes, KLF1 encourages HbF repression, which is regulated by changing myeloblastosis expression. Conclusion: This study shows that the genes KLF1 and MDM2 are related to dysregulated molecular pathways, contribute to the development of beta thalassemia, and may be exploited as a platform for the induction of fetal hemoglobin in the development of therapeutics.

Hypogonadism among patients with transfusion-dependent thalassemia: a cross-sectional study.

The authors conducted this cross-sectional study in the Kurdistan Region of Iraq, from 1 July 2022, to 1 December 2022. Eighty patients with β-thalassemia major who were referred to the endocrinology clinic were enrolled. The patients were evaluated sequentially, starting with a history, followed by a clinical examination and laboratory tests related to endocrine disease. Those who met the inclusion criteria were enrolled in the study, while the others were excluded. Out of 80 patients with major thalassemia who were referred to the endocrinology clinic, 53 (66.3%) were female, and 27 (33.7%) were male, with a mean (SD) age of 24.86±7.66 (14-59) years. Fifty-five (68.75%) of them had hypogonadism, three patients (3.8%) had hypothyroidism, while two (2.5%) had hypoparathyroidism. Five patients (6.3%) had diabetes. None of the patients had adrenal insufficiency. The mean ferritin level in thalassemic patients with hypogonadism and thalassemic patients without hypogonadism was 2326±2625ng/ml vs. 1220±2625ng/ml. To minimize the risk of endocrinopathy in patients with thalassemia major, they should receive blood transfusions regularly and initiate chelating agents early, because the leading cause of endocrinopathy in thalassemic patients is related to the severity of anemia and iron overload.

Spurious Thrombocytosis in Beta Thalassemia Intermedia – Even AutoAnalyzers Do Get Perplexed!

Spurious Thrombocytosis in Beta Thalassemia Intermedia – Even AutoAnalyzers Do Get Perplexed!

Estimated Level of Plasma Micro RNA-210 in Beta Thalassemia Patients and Its Relation to Hemoglobin F Level and Disease Severity

BACKGROUND: Beta-thalassemia is an autosomal recessive hereditary blood disorder occurs due to absent or diminished β-globin chains synthesis. The transformation from fetal to adult in globin synthesis is controlled by different mechanisms; one of those is BCL11A which is downregulated by microRNA-210 (miRNA-210). Therefore, this would lead to reactivation of fetal hemoglobin (HbF) production that improves anemia and reduces the needs for transfusion. OBJECTIVE: To study miRNA-210 in the plasma of beta thalassemia patients and its relation to HbF level and disease severity. SUBJECTS AND METHODS: The study was carried out on 50 individuals divided into three groups. Group A included 30 thalassemia major patients, Group B included 10 thalassemia intermedia patients, and Group C is 10 healthy volunteers as control. All individuals underwent to history taking, physical examination, and laboratory investigations, complete blood count, serum ferritin, hemoglobin electrophoresis, and measurement of miRNA-210 expression levels in plasma of peripheral blood samples by quantitative real-time polymerase chain reaction. RESULTS: Examination of miRNA-210 plasma level among different groups revealed no statistically significant association between control and thalassemia group or its subgroups (Major and intermedia) (P = 0.224, P = 0.116, and P = 0.734, respectively). Moreover, miRNA-210 was slightly higher in responders than nonresponders to hydroxyurea but did not reach significant level. CONCLUSION: miRNA-210 levels were not associated with increase in HbF levels in thalassemia patients.

Status Nutrisi dan Hemoglobin Setelah Pemberian Transfusi pada Penderita Thalasemia

More than 5,000 babies are born suffering thalassemia (beta thalassemia major and beta thalassemia Hb E) annually from around the world and 80% of births occur in developing countries (Kantharaj & Chandrashekar, 2018). In Indonesia alone, the frequency of beta thalassemia genes ranges from 3-10% with 2,500 babies born each year and there are 10,531 more patients experiencing thalassemia (Kemenkes, 2019). The general objective of this study was to identify the relationship between nutritional status and changes in hemoglobin levels after transfusion in children with thalassemia at RSD Gunungjati Cirebon. This research method uses descriptive correlation by using a cross sectional. The sample of this research is thalassemia in Gunung Jati Hospital, Cirebon City, totaling 35 respondents using accidental sampling technique. The instrument used is a data and measurement recapitulation sheet. The nutritional status data recapitulation sheet containing components (gender, age, weight, TB) and measurement of Hb before and after blood transfusion using EasyTouch GCHB, as well as data analysis using the Spearman rank, was carried out on July 4-15, 2022. The results of the univariate analysis of the study This is in the category of good nutritional status as many as 18 respondents (51.4%) and an increase in hemoglobin levels of 18 respondents (51.4%) in thalassemia children at Gunungjati Hospital, Cirebon. The results of this study found that there was no relationship between nutritional status and changes in hemoglobin levels in thalassemia children at RSD Gunungjati Cirebon with a value (p = 0.252 > = 0.05).Suggestions for this study are that families and patients should strive to carry out the education provided by nurses and explore more knowledge related to thalassemia, especially nutritional intake.

The beta thalassaemia trait in Jamaica.

The objective of this study was to review the prevalence and features of the beta thalassaemia trait in Jamaican populations. Screening of 221,306 newborns over the last 46 years has given an indication of the distribution and prevalence of beta thalassaemia genes, and screening of 16,612 senior school students in Manchester parish, central Jamaica, has provided their haematological features. The prevalence of the beta thalassaemia trait predicted from double heterozygotes was 0.8% of 100,000 babies in Kingston, 0.9% of 121,306 newborns in southwest Jamaica, and 0.9% of school students in Manchester. Mild beta+ thalassaemia variants (-88 C>T, -29 A>G, -90 C>T, polyA T>C) accounted for 75% of Kingston newborns, 76% of newborns in southwest Jamaica, and 89% of Manchester students. Severe beta+ thalassaemia variants were uncommon. Betao thalassaemia variants occurred in 43 patients and resulted from 11 different variants of which the IVSII-849 A>G accounted for 25 (58%) subjects. Red cell indices in IVSII-781 C>G did not differ significantly from HbAA, and this is probably a harmless polymorphism rather than a form of beta+ thalassaemia; the removal of 6 cases in school screening had a minimal effect on the frequency of the beta thalassaemia trait. Red cell indices in the beta+ and betao thalassaemia traits followed established patterns, although both were associated with increased HbF levels. The benign nature of beta+ thalassaemia genes in Jamaica means that cases of sickle cell-beta+ thalassaemia are likely to be overlooked, and important clinical questions such as the role of pneumococcal prophylaxis remain to be answered.

A Comprehensive Review of Pregnancy in Sickle Cell Disease.

Sickle cell hemoglobinopathies encompass a range of qualitative and quantitative hemoglobin disorders that are inherited genetically. This group of disorders includes sickle cell beta thalassemia, sickle cell trait, and sickle cell disease (SCD). Globally, SCD is the most common disorder. Even epidemiological data suggests the majority of diseases, as well as traits, are concentrated in Sub-Saharan Africa, North-East Africa, the Middle East, and India. The physiological changes in pregnancy predispose to an increased risk of catastrophic events like a vaso-occlusive crisis, thromboembolic events, and their related sequelae, leading eventually to villous infarction, necrosis, and fibrosis leading to compromising uteroplacental circulation. Conversely, the mother may exhibit exacerbated symptoms of gestational hypertension, placental abruption, preterm labor, and venous thromboembolism. Although this disease is manageable, it has the potential to adversely impact maternal and child health on a national level. The chances of severe complications in the pregnant state affecting both mother and fetus attract due attention of health services towards redefining and researching this disease and its management frequently. The literature review on the following situation advocates the general treatment to be observed under the headings of preconceptual care, strengthened antenatal care, strict intranatal care, and compliant post-natal care. Preconceptually, genetic screening of couples, with education on the adverse effects of the disease, comes as the first line of management. Newer facilities like preimplantation genetic diagnosis and celocentesis may even allow for early diagnosis as well as help patients who do not wish to terminate the pregnancy by selective transfer of unaffected embryos. This may be combined with an extensive evaluation of the psychosocial aspect and socioeconomic status of couples who administer vaccines as prophylaxis for preventable diseases. Strengthening antenatal care is associated with routine blood investigations for every registered antenatal patient with adequate awareness about the conditions that precipitate the crisis. All patients should be prophylactically treated with appropriate doses of aspirin, iron, folic acid, and multivitamins. Radiological examinations by ultrasonography may be used to monitor placenta previa, abruption, or preterm labor. Later in pregnancy, it should be recommended to performbiophysical profiling and assessment of umbilical artery flow. Intranatal care deals with strict-term institutional delivery of all sickle cell-diseased mothers with a preference for vaginal delivery. Post-natal care requires a precise assessment of blood loss during labor to initiate transfusion therapy as soon as needed. Exclusive breastfeeding, with the importance of early initiation of it, must be emphasized. Screening of neonates as quickly as possible must be done for hemoglobinopathies. Through this review, authors are trying to make aware of the complications that can be faced during pregnancy in SCD patients, its prevention, and its treatment according to various new guidelines and research available.

Differentiation of Beta Thalassemia Trait from Iron Deficiency Anemia by Hematological Indices

Differentiation of Beta Thalassemia Trait from Iron Deficiency Anemia by Hematological Indices

Knowledge, Attitudes and Practices Regarding the Prevention of Thalassemia in Parents of Thalassemic Children in Swat

Introduction: Thalassemia is a set of inherited disorder caused by a partial or complete mutation in one or more chain of the globin genes. Beta Thalassemia is the most common genetic disorder throughout the world including in Pakistan. Objectives: To assess the knowledge, attitudes and practices of parents of the children suffering from Thalassemia with regards to disease prevention. It also determined the degree of social and religious opposition faced by these parents during implementation of preventive practices Methods: A descriptive cross-sectional survey was conducted in district Swat, KP, via three regional thalassemia centers. Total of 200 parents of Thalassemia were interviewed using a pre-designed pre-tested structured questionnaire. All statistical analyses were conducted using Statistical Package for Social Sciences (IBM SPSS 23.0) Results: Out of the total participants, male parents were (67.7%), while females were (32.3%). A total of responses were gathered, and analyzed. Most respondents had adequate knowledge positive attitude towards thalassemia. Age, education, gender, and family income were key factors that correlated with or predicted the youth’s KAP towards thalassemia. Older respondents and women were more likely to have good KAP. 77.5% of parents opted for prenatal diagnosis, and 77% opted for termination of the affected fetus. Among these individuals, 7.5% faced opposition from their family members when they went for diagnostic testing, and this opposition rose to 18.5% when they had to opt for termination. The local religious clerics opposed prenatal diagnosis in 3.5% of the cases and termination in 4% of the cases. Conclusions: When compared to previous studies, the knowledge, attitudes, and practices of our study population were better. Thus, population screening programs have a positive impact on the knowledge, attitudes, and practices of careers of thalassemia patients. However, social and religious opposition needs to be countered for further implementation of effective preventive practices.

Global burden and unmet needs in the treatment of transfusion-dependent β-thalassemia

Beta thalassemia (β-thalassemia) is part of a group of inherited hemoglobinopathies caused by a mutation in the beta globin gene, leading to minimal functional hemoglobin and resulting in damaged red blood cells and anemia. β-Thalassemia is most common in the Mediterranean region, South-East Asia, the Indian subcontinent, and the Middle East. Many of these regions include low- and middle-income countries where there are significant unmet needs in the adequate care and management of thalassemia. Patients with transfusion-dependent β-thalassemia, the most severe form of the disease, require regular blood transfusions. Chronic transfusions are often accompanied by iron chelation therapy to manage ferritin levels. Complications caused by transfusions and iron overload are only partially addressed by current treatment strategies, which negatively affect the quality of life of patients with transfusion-dependent β-thalassemia. Until curative modalities become available for all patients worldwide, methods of optimizing supportive treatments are needed to reduce the symptoms of ineffective erythropoiesis; minimize transfusion-related reactions and side effects; reduce rates of alloimmunization and transfusion-transmitted infections; and to reduce the psychosocial burden on both patients and their caregivers. This review aims to provide an overview and comparison of the ways transfusion-dependent β-thalassemia is identified and treated in different geographic regions, to assess unmet needs specific to these regions, and to discuss how therapies currently in development may improve care.

Thalassemia and Hemoglobinopathy Screening in Women Attending Antenatal Clinic at a Tertiary Care Center in Uttarakhand, India: A Re-look at the Laboratory Parameters Mandating High-Performance Liquid Chromatography Workup.

Thalassemia and hemoglobinopathies are the most common inherited hematological disorders. Of these, β thalassemia is the commonest disorder reported in India, followed by certain hemoglobinopathies encountered in different regions of the country. The data pertaining to the incidence of these disorders in the Uttarakhand region of India are sparse. To ascertain the prevalence and spectrum of thalassemia/hemoglobinopathies amongst antenatal women in Uttarakhand. The study also aimed to analyze the ability of red cell indices in differentiating beta thalassemia trait (BTT) from mild iron deficiency anemia (IDA). A total of 460 pregnant women in the first trimester of pregnancy were screened by cation exchange high-performance liquid chromatography. Retention time and proportions of normal/abnormal hemoglobin peaks were documented in all cases. Hemoglobin A2 (HbA2) values of ≥4% were taken as a cut-off for diagnosing BTT. Blood samples were also collected for complete blood counts, reticulocyte counts, and serum ferritin. The ability of the various discriminatory indices to differentiate between IDA and BTT was also assessed. The prevalence of BTT and hemoglobin D-Punjab trait amongst pregnant women was found to be 2.6% and 0.2%, respectively. RBC count, mean corpuscular volume (MCV), and mean corpuscular hemoglobin (MCH) were found to be moderately strong predictors of BTT, with an area under the curve of 0.860, 0.857, and 0.842, respectively, which were comparable to the discriminatory indices found to be most useful in this study. In view of the 2.6% prevalence of BTT in antenatal women in this region of Uttarakhand, a routine screening will be helpful in detecting carriers early in the antenatal period. Careful interpretation of red cell indices is crucial to the distinction between BTT and IDA. Discriminatory indices are reasonably accurate in differentiating BTT from mild iron deficiency, but for practical purposes, MCV and MCH provide equivalent information to identify cases that require further workup.

Assessment of glucose homeostasis in young adult female β-thalassemia major patients (β-TM) with acquired hypogonadotropic hypogonadism (AHH) never treated with sex steroids compared to eugonadal β-TM patients with spontaneous menstrual cycles.

Acquired ypogonadotropic hypogonadism (AHH) is the most prevalent endocrine complication in thalassemia major (TM). Considering the detrimental effect of estrogen deficiency on glucose metabolism, the ICET-A Network promoted a retrospective study on the long-term effects of estrogen deficiency on glucose homeostasis in female β-TM patients with HH without hormonal replacement therapy (HRT). Seventeen β-TM patients with AHH (4 had arrested puberty; Tanners' breast stage 2-3), never treated with sex steroids, and 11 eugonadal β-TM patients with spontaneous menstrual cycles at the time of referral were studied. A standard 3-h OGTT was performed in the morning, after an overnight fast. Six-point plasma glucose and insulin level determinations, indices of insulin secretion and sensitivity, early-phase insulin insulinogenic index (IGI), HOMA-IR and β-cell function (HOMA-β), oral disposition index (oDI), glucose and insulin areas under the OGTT curves were evaluated. Abnormal glucose tolerance (AGT) or diabetes was observed in 15 (88.2%) of 17 patients with AHH and 6 (54.5%) of 11 patients with eumenorrhea. The difference between the two groups was statistically significant (P: 0.048). However, the group of eugonadal patients was younger compared to AHH patients (26.5 ± 4.8 years vs. 32.6 ± 6.2 years ; P: 0.010). Advanced age, severity of iron overload, splenectomy, increased ALT levels and reduced IGF-1 levels were the main clinical and laboratory risk factors for glucose dysregulation observed in β-TM with AHH compared to eugonadal β-TM patients with spontaneous menstrual cycles. These data further support the indication for an annual assessment of OGTT in patients with β-TM. We believe that a registry of subjects with hypogonadism is necessary for a better understanding of the long-term consequences of this condition and refining treatment options.

Correlation Between Adherence Therapy of Iron Chelation Levels with Anthropometric Status in Major Beta-Thalassemia Patients

Thalassemia is a condition in which hemoglobin undergoes hemolysis due to impaired synthesis of hemoglobin or globin chains. Growth failure is a common occurrence in patients with thalassemia. Iron overload due to repeated transfusions will cause disturbances in anthropometric status in children with thalassemia. Iron chelation therapy is needed to overcome iron overload in patients with beta-thalassemia major. The level of adherence affects the success of iron chelation therapy. This study aims to determine the relationship between the level of adherence to iron chelation treatment and anthropometric status in patients with thalassemia beta major at Kediri District General Hospital. This type of research is observational analytic with a cross-sectional design. This research was conducted at the SMF Pediatrics (IKA) RSUD Kediri Regency on 16 subjects with B-thalassemia major using a total sampling technique that met the inclusion criteria. The research instruments used in this study were the Morisky Medication Adherence Scale-8 questionnaire and an examination of anthropometric status. The research analysis used the Spearman correlation test. A p-value <0.05 was considered significant. The results showed that there was a significant results between adherence to iron chelation consumption and height for age (p-value = 0.049 > a 0.05), significant results between adherence to iron chelation consumption with weight for age (p-value = 0.036 < a 0.05), and significant results with weight for height (p-value = 0.001 < a 0.05). This study implies that adherence to iron chelation therapy is essential for thalassemia patients. This study shows that patients more adherent to iron chelation treatment have better anthropometric status.

Assessment of serum fractalkine level as potential role for complications in splenectomized and non-splenectomized patients with β-thalassemia major

Introduction: Thalassemia is a serious genetic blood related condition characterized by a lack of or malfunctioning hemoglobin in the RBCs. One of the most widespread inherited disorders is beta thalassemia (β-TM). The high susceptibility to infection in these individuals' is related to high mortality and morbidity rates. Fractalkine is known as CX3C chemokine ligand 1 (CX3CL1), which contains a total of 371 amino acid, and participates in a number of functions, including repair of tissues after injury, immunological response during inflammation, and chemotaxis effet.
 Methodology: A case control study, containing sixty patients recognized as suffering from β-TM, was conducted at Al Zahra Teaching Hospital, Najaf (Iraq). The patients were divided into two groups; splenectomized and non-splenectomized patients. The thalassemia disease was enrolled in the “Thalassemia Unit”. Suitable statistical techniques were used to analyze the outcomes.
 Results: In the current study, a significant increase in serum level of CX3CL1 was found in patients with β-TM, especially in splenectomized group (14.914 ± 2.636), (P = 0.01) and non-splenectomy (13.816 ± 2.686), (P = 0.05) group as compared with control group (12.26 ± 1.797).The linear regression analysis showed that a significant positive correlation in ferritin with serum CX3CL1 level in splenectomy patients with β-TM group. ROC curve for CX3CL1 that might be diagnosis of patients with β-TM with an AUC of 0.757 (95% CI: 0.623-0.890), sensitivity and specificity equally 75% and 83.3%.
 Conclusion: Increase level of CX3CL1 due to its interaction with CX3CR1 receptor may lead to buildup of inflammatory cells in the β-TM patients, blocking CX3CL1 signaling may be helpful for patients with β-TM.
 Abbreviations: AUC – Area Under Curve; β-TM - Beta Thalassemia; ROC - Receiver Operating Characteristic UIBC - Unsaturated Iron-Binding Capacity test; TIBC - Total Iron-Binding Capacity
 Key words: Thalassemia, β thalassemia major, Fractalkine
 Citation: Awad AS, Ali HA, Althalmi SAA. Assessment of serum fractalkine level as potential role for complications in splenectomized and non-splenectomized patients with β-thalassemia. Anaesth. pain intensive care 2023;27(5):495−500; DOI: 10.35975/apic.v27i5.2302
 Received: August 03, 2023; Reviewed: August 12, 2023; Accepted: August 14, 2023

Correlation between Adherence Therapy of Iron Chelation Levels with Serum Ferritin Levels in Major Beta-Thalassemia Patients at Kediri District General Hospital

Repeated transfusions, increased absorption of iron, and ineffective erythropoiesis in patients with B thalassemia major cause iron overload, characterized by increased ferritin levels. Iron chelation therapy is needed to overcome iron overload in patients with beta-thalassemia major. The level of adherence affects the success of iron chelation therapy. This study aims to determine the relationship between adherence to iron chelation treatment and serum ferritin levels in patients with thalassemia beta major at Kediri District General Hospital. This type of research is an observational analytic with a cross-sectional design conducted on 17 subjects of B-thalassemia major patients at Pediatric Health Sciences (IKA) RSUD Kediri Regency who met the inclusion and exclusion criteria in December 2022-January 2023. The interviews used the Morisky Medication Adherence Scale questionnaire. -8, while the serum ferritin examination was obtained from the patient's medical record. There were 17 respondents who obeyed 11.76%; the non-compliant category was carried out by Spearman's correlation test and obtained a value of p = 0.01 and a value of r = -0.559. This shows significant results, and there is a moderate correlation between the level of adherence to iron chelation treatment and serum ferritin levels in beta-thalassemia major patients at Kediri District Hospital.

Comparison of HbA2 Using High Performance Liquid Chromatography Versus Haemoglobin Capillary Zone Electrophoresis.

Thalassemia is among the most common hereditary disorders in the world. Approximately 5% of the world's population are carriers of hemoglobinopathies, and 2.9% are carriers of beta thalassemia. Haemoglobin A2 (HbA2) constitutes less than 3% of the total hemoglobin (Hb) in adults, and the determination of Hb A2 levels is important to diagnose the beta thalassemia trait(BTT). In some cases, the level of HbA2 is not typically elevated, and some difficulties may arise in making the diagnosis. Cation exchange high-performance liquid chromatography (HPLC) and HbCZE (haemoglobin capillary zone electrophoresis) are considered acceptable methods to diagnose BTT, but these vary in their accuracy and cut-offs. In this study, we attempted to compare HbA2 values using two methods, HPLC and HbCZE, in 536 whole blood samples sent by physician-ordered hemoglobinopathy screening over two years. This included antenatal women, patients with anemia not responding to iron, and cases of familial screening where either a child or a sibling had been diagnosed with hemoglobinopathy or thalassemia. The performance characteristics of both machines were compared for the detection of the 5 most common hemoglobin variants: Hb A, HbF, HbS, Hb C, and HbE. On comparing the HbA2 values, the HPLC showed higher values for HbA2 as compared to HbCZE, while the HbF and HbS measurement agreement was good between both methods. Normal ranges and mean normal values of HbA2 differ between different methods and different manufacturers; hence, each institute using these machines should validate its cutoffs.

Malignancy in patients with sickle cell disease: A single center experience.

e22551 Background: The development of malignancy in patients with sickle cell disease has been documented in multiple case reports and case series. The incidence of malignancy in patients with sickle cell disease is unknown. Large national databases like the National Cancer Database, North American Association of Central Cancer Registries, and SEER do not collect data on the presence of sickle cell disease. This has made it difficult to calculate the incidence of malignancy in this patient population. In our study, we aim to calculate the prevalence of malignancy in sickle cell patients following our institution. Methods: After IRB approval, a retrospective analysis was conducted of adult sickle cell disease patients being followed at our Hematology outpatient clinic. We included patients aged > / = 18 years with sickle cell disease (HBSS, HBSC, HBS-beta thalassemia) as per hemoglobin electrophoresis, who were followed at the clinic from 1/1/2017 to 10/1/2022. We excluded prisoners. We did an extensive chart review to identify patients with a diagnosis of malignancy by pathology. Variables of age, sex, race, type of sickle cell disease, type of malignancy, age at the diagnosis of malignancy, and treatment were collected. Continuous descriptive data were summarized as means. Categorical data were summarized with a sample percentage. The prevalence of malignancy was calculated. SAS for windows 9.4 was used for analysis. Results: 438 patients with sickle cell disease were identified from 2017 to 2022. All the patients were African American. Their ages ranged from 16 to 84 with a mean of 35 years. Of these patients 53 % were females and 47 % were male. 62% had HBSS disease, 25 % had HBSC and 13% had HBS beta thalassemia genotype. 4 patients were diagnosed with malignancy. All 4 patients were female. The prevalence of malignancy was calculated as 0.91%. Conclusions: We found four patients with malignancy in the patient population with sickle cell disease at our hematology clinic. This data is based on limited sample size. The incidence of malignancy in sickle cell patients should be calculated in a larger population base. Further studies can be done to determine if a single type of sickle cell genotype increases the risk of malignancy. All the centers where sickle cell patients are followed should monitor the patients prospectively for the development of malignancy.[Table: see text]

CLINICOETIOLOGICAL STUDY OF HEMOLYTIC ANAEMIA IN CHILDREN PRESENTING TO A TERTIARY CARE HOSPITAL OFKASHMIR

Anemia is said to be present when the hemoglobin levels are more than two standard deviations below the mean for the childs age and sex. Hemolytic anemias arise when red blood cells have decreased survival either due to an intrinsic abnormality of the cell or due to extrinsic factors or both. Hemolytic anemias constitute important cause of mortality and morbidity in developing countries. These group of anemias have various clinical presentations starting from their age of onset of symptoms, failure to thrive, anemia, jaundice, splenomegaly, cholelithiasis, cardiomegaly, congestive cardiac failure, severe life-threatening infections and chronic disabilities leading to distress in the families. The present study attempts to reveal the clinical and etiological profile of patients with different types of hemolytic anemia admitted in a pediatric tertiary care hospital of Kashmir. Review of literature shows only few epidemiological studies particularly in this part of the country, and no such study in our state though the disease is fairly prevalent. We undertook this study with this idea. Aims and Objectives: The aims and objectives of this study was to determine clinical and etiological profile of hemolytic anemia in children aged 1month to 18 years admitted in tertiary care hospital of Kashmir. Materiaals & Methods: This prospective observational study was carried out in a pediatric tertiary care hospital in Kashmir over a period of two years. Prior to initiation of study, ethical clearance was obtained. All patients admitted in the indoor of department of pediatrics between age group of 1 month to 18 years with evidence of hemolysis were included in the study. 50 cases were included in the study after obtaining written informed consent from parent or guardian. A detailed history, examination and required investigations were collected. Data was entered and assessed in MS Excel. Results: The study was based on 50 patients, almost equal males and females, 1month to 18 years of age. The most common hemolytic anemia was beta thalassemia major (n=17, 34%), followed by autoimmune hemolytic anemia(n=10,20%), hereditary spherocytosis (n=5,10%), thalassemia trait (8%), pyruvate kinase deficiency (8%) and glucose 6 phosphate dehydrogenase (8%), thalassemia intermedia (4%), sickle cell trait (2%), microangiopathic hemolytic anemia (2%), hereditary xerosis (2%) and hereditary stomatocytosis (2%). Highest number of the cases was less than 3 years old (56%). The most common clinical presentation was jaundice, which was present in all cases, followed by splenomegaly (60%), hepatomegaly (30%), hemolytic facies (26%). Splenomegaly was seen in all cases of thalassemia major, thalassemia intermedia, beta thalassemia trait, hereditary spherocytosis, 2 cases of pyruvate kinase deficiency and 3 cases of glucose 6 phosphate dehydrogenase deficiency. Spleen >5cm was seen in 10 patients. Massive splenomegaly with abdominal discomfort was seen in 3 cases. The mean hemoglobin was least in beta thalassemia major followed by beta thalassemia intermedia, Hereditary spherocytosis, autoimmune hemolytic anemia, glucose 6 phosphate dehydrogenase deficiency and the highest mean hemoglobin was seen in pyruvate kinase deficiency. Means for serum ferritin and serum bilirubin were calculated.

Correlation between Short Stature with Serum Ferritin Levels in Major Beta-Thalassemia Patients at Kediri District General Hospital

In thalassemia, a lifelong sequence of blood transfusions leads to iron overload characterized by increased ferritin levels. Many factors, including iron overload may cause growth delay. High ferritin levels are believed to lead to short stature in children with thalassemia. This study aims to determine the correlation between short stature and ferritin levels in children with major beta thalassemia at Kediri District General Hospital. This research is an observational analytic with a cross-sectional design conducted on 17 subjects of beta thalassemia major patients at Pediatric Health Sciences (IKA) Kediri District General Hospital who met the inclusion and exclusion criteria in December 2022-January 2023. The measuring instrument used in this study was anthropometric status, explained through age stature, while the ferritin levels was obtained from the patient's medical record. Spearman's rank order correlation test was used in the analysis. There were 17 respondents, 82,36% children in short categories and 17,64% in normal categories. The Spearman correlation test has the p-value = 0.000 and r = -0,736. A strong negative correlation exists between short stature and ferritin levels in beta-thalassemia major patients at Kediri District General Hospital that means the higher ferritin levels, the higher incidence rate of short stature.

The potential benefits and risks of sex-steroids therapy in thalassemic patients with hypogonadism

Introduction: A recent review from 14 Mediterranean and Middle East countries (n =4477, mean age = 16.5 years) showed that the pooled prevalence of delayed puberty / hypogonadism in patients with BTM was 45.6%. Studying the consequences of hypogonadism and the potential benefits versus unwanted side effects of sex-steroid hormone replacement therapy (HRT) in children and adolescents with Beta Thalassemia Major (BTM) represent an important issue for these patients. Objectives: We reviewed the literature (Pubmed, Google scholar, Scopus, Research gate) (1995: 2022) on the consequences of hypogonadism and benefits versus side effects of using sex Steroid therapy (HRT) in hypogonadal adolescents with BTM. Thirty-five papers were included and analyzed. Results: HRT had a variable but significant beneficial effect on improving bone mineral density (BMD), pubertal growth spurt, development of secondary sexual characteristics and subsequently improved quality of life (QOL) in children and adolescents with BTM. Increased side effects of HRT in these patients may occur due to their state of hypercoagulability especially in splenectomized patients and those with cardiomyopathy, chronic hepatitis, and dysglycemia. Gynecomastia and local pain in the site of injection confirmed in a considerable number of males on testosterone therapy. Local reaction to sex steroid patches appeared in around 30% of patients. Based on this review recommendations for using HRT in these patients were updated. Conclusion: Proper and wise use of sex steroid therapy in patients with BTM can significantly improve many consequences of hypogonadism.