Beta Thalassemia Major Research Articles

Estimation of Serum Cystatin-C as early marker of Kidney Dysfunction in correlation with Serum Ferritin among β- Thalassemia Major Patients

The Cystatin C is early predictor for evaluation the kidney functions. The Serum Cystatin C is a cysteine proteinase inhibitor, that the nucleated cells produce it at stable rate. It is filtered through the glomerular filtration membranes of kidneys, and the filtration rate will be unaffected by external factors. A group of recessively inherited hemoglobin disorders called Major Beta-thalassemia and considered the most common genetic disorder all over the world, which could be noticed by the reduction in of β-globin chain synthesis.Objective: To study Serum Cystatin-C estimation as early marker of renal function in relation with other parameters in beta thalassemia patients.Materials and Method: A case-control study was executed on thalassemia patients between February and April 2019 at Al-Zahra’a Teaching Hospital in Najaf/Iraq.Results: the results in this study showed there are significant differences (p< 0.05) between major beta thalassemia patients and control group in regarding to hematological parameters. The result of biochemical parameters showed there are variations between patients and control where there were significant statistical increases in our thalassemic patients comparing to the control about Cystatin-C (1.27±0.33and 0.7±0.24 ng\ml respectively).Conclusion: the cystatin –C is useful marker at major beta thalassemia patients that suffering from renal dysfunction

Beta Thalassemia Major: Overview of Molecular Etiology, Pathophysiology, Current and Novel Therapeutic Approaches

Major beta thalassemia is a severe form of thalassemia caused by the alteration of two beta globin genes resulting in a defective synthesis of hemoglobin.&#x0D; It is characterized by chronic severe anemia, ineffective erythropoiesis (IE) and iron overload. However although the thransfusion and chelation assosciated constitute the basis of the traitement curently recommended, they do not allow always to control the iron overload induced by pathology and repeated transfusions.&#x0D; Hematopoietic stem cell transplantation (HSCT) has proven to be a definitive treatment for beta thalassemia. However, this procedure is confronted to immunological complications and the small nomber of histocompatible donors. In the face of these therapeutic blocks, much research has been undertaken in recent years leading to the development of a number of promising therapeutic strategies in order to reduce the constraints linked to current chronic treatments, and to move towards an access to healing for all patients. Among other three approaches are envisaged and are in the experimental phase: Gene therapy to restore globin chain imbalance, Improve ineffective erythropoiesis and Improve iron dysregulation. In this article we give a view on the pathophysiology, clinical manifestations, genetic origin of beta-thalassaemia major. The second part presents the therapeutic arsenal currently used, and its limits leading to therapeutic impasse. The last part explores the scientific tracks that present a real therapeutic potential in β-Thalassemia.

Platelet Refractoriness during BONE Marrow Transplantation, Comparison in Aplasticanemia and Beta Thalassemia Major Patients.an Experience of Public Sector BMT Unit in Pakistan

<h3>Background</h3> Bone Marrow Transplantation (BMT) is curative treatment modality for many Hematological and oncological diseases. This treatment is commonly available in developed countries but Lower middle income countries (LMICs) like Pakistan this facility is not available easily. We had established first Public sector BMT center at the Children Hospital & Institute of Child Health, Lahore, Pakistan in collaboration with NIBD &BMT, Karachi, Pakistan. This BMT center is providing free of cost HSCT facility to the children of poor families. This unit is financially supported by the Government of Punjab, Pakistan. So we as BMT Physicians have the ethical and moral responsibility to save the expenses and decrease the undue expenditure. In this regard we had noticed that a handsome amount of money is being consumed for platelet transfusions during BMT. Platelet transfusions reduce the major Hemorrhagic complications during BMT but refractoriness to infused platelets is a major clinical problem as well as huge financial burden. <h3>Objective</h3> To measure the frequency of Platelet refractoriness and comparison in Aplastic Anemia (AA) and Beta Thalassemia Major (BTM) during BMT. <h3>Methods & Materials</h3> This study done at BMT unit, Children Hospital & Institute of Child Health, Lahore, Pakistan after approval from ethical committee. Platelet refractoriness is confirmed by the "lack of platelet count rise (> 10,000 × 109 /l) after one hour of a single Mega unit Platelet transfusion. No HPA antigen or antibodies or HLA antibodies identified because of financial constraints <h3>Results</h3> Total 19 patients included in study, AA patients were 11 and 08 were of BTM In our experience, platelet refractoriness is more common in the patients of beta Thalassemia than that of Aplastic Anemia. The only 2/11 Aplastic Anemia patients showed platelet refractoriness while 6/08 of Beta Thalassemia had platelet refractoriness <h3>Conclusion</h3> Platelet Refractoriness is more common in BTM patient in comparison with AA patients during Bone marrow Transplantation. Our study is also indirect evidence that the PRBC transfusions can also produce antibodies responsible for platelet refractoriness. <h3>Discussion</h3> BTM patients are immunocompetent and can produce antibodies for RBC as well as platelets after PRBC transfusions. Aplastic Anemia patients are less Immunocompetent so the possibility of antibody production for RBCs and Platelets are least. One more reason is less number of transfusions in AA than BTM due to urgent need of BMT. <h3>Recommendation</h3> We recommend to Physicians who are involved in the management of BTM patients that the Red cell Extended Phenotyping should be done before putting the patients on chronic PRBCs transfusion therapy. This strategy ultimately decreases the complications of alloimmunisation both for PRBCs and Platelet. Hence decrease the financial burden on the family as well as on Hospital in LMICs at least.

Change in Attitude in Renal Function in Major Beta Thalassemia

Thalassemia is a multisystemic disease in the field of hemolysis and chronic anemia caused by the erythropoietic disorder. The severe effects of iron overload from continuous blood transfusion iron chelators side effects, and involvement of multiple organs in thalassemias such as heart failure, liver, and endocrine dysfunction can all affect kidney function. Although there has been much debate about changes in renal function in thalassemia for many years, the presence of hyperfiltration and ultimately, decreased renal function in almost all studies. It seems for the researchers to look beyond kidney function in a thalassemia perspective, because of secretory biomarkers of proximal tubular renal cells that are sensitive to pathologic agents, which may be a good indicator of the courses of treatment and prognosis of patients. Future studies will be sooner or later. *Corresponding Author: Malihe Najafpour; Email: malihe_najafpour@modares.ac.ir Please cite this article as: Malaki M, Najafpour M, Talebi M, Azimi A. Change in Attitude in Renal Function in Major Beta Thalassemia. Arch Med Lab Sci. 2020;6:1-5 (e24). https://doi.org/10.22037/amls.v6.33057

Estimation of Serum Homeostasis Model Assessment-Insulin Resistance and Lipid Profile in Beta-thalassemia Major Patients and their Correlation with Iron Overload in Koya City

The current study focused on 43 patients who suffer from major beta-thalassemia at the hospital of shaheed Dr. Khaled in the Koya city. Out range, age of cases was 8.03 ± 4.0 and of controls was 7.81 ± 3.11 years. Our aim is to observe the prevalence of homeostasis model assessment-insulin resistance and other physiological and biochemical changes in major beta-thalassemia. While we a significant changes confirm that serum glucose concentration was significantly higher in the patients than in the controls (P ≤ 0.01) and lipid abnormality occurs in beta-thalassemia major patients, which include high-density lipoprotein-cholesterol (HDL-C), low-density lipoprotein-cholesterol (LDL-C), serum total cholesterol (TC), serum triglycerides (TG), and very-low-density lipoprotein (VLDL) levels compared with normal healthy controls. There was no significant difference between the serum insulin level of cases and controls (P = 0.214), the mean values of serum HDL-C, LDL-C, TC, TG, and VLDL in cases were 29.5 ± 7.8, 65.2 ± 1.9, 121.9 ± 36.7, 182.09 ± 43.1, and 26.47 ± 12.13 mg/dl, respectively. Moreover, the mean values of serum HDL-C, LDL-C, TC, TG, and VLDL in controls were 48.6 ± 4.2, 79.7 ± 14.5, 178.7 ± 14.6, 124.14 ± 12.1, and 23.52 ± 5.47 mg/dl, respectively. In conclusion, the results suggested that revealed that beta-thalassemia patients had hypertriglyceridemia, hypocholesterolemia, and low LDL-C, and HDL-C levels.

Recent Progress in Gene Therapy and Other Targeted Therapeutic Approaches for Beta Thalassemia.

Beta-thalassemia is a genetic disorder characterized by the impaired synthesis of the betaglobin chain of adult hemoglobin. The disorder has a complex pathophysiology that affects multiple organ systems. The main complications of beta thalassemia are ineffective erythropoiesis, chronic hemolytic anemia and hemosiderosis-induced organ dysfunction. Regular blood transfusions are the main therapy for beta thalassemia major; however, this treatment can cause cardiac and hepatic hemosiderosis - the most common cause of death in these patients. This review focuses on unique future therapeutic interventions for thalassemia that reverse splenomegaly, reduce transfusion frequency, decrease iron toxicity in organs, and correct chronic anemia. The targeted effective protocols include hemoglobin fetal inducers, ineffective erythropoiesis correctors, antioxidants, vitamins, and natural products. Resveratrol is a new herbal therapeutic approach which serves as fetal Hb inducer in beta thalassemia. Hematopoietic stem cell transplantation (HSCT) is the only curative therapy for beta thalassemia major and is preferred over iron chelation and blood transfusion for ensuring long life in these patients. Meanwhile, several molecular therapies, such as ActRIIB/IgG1 Fc recombinant protein, have emerged to address complications of beta thalassemia or the adverse effects of current drugs. Regarding gene correction strategies, a phase III trial called HGB-207 (Northstar-2; NCT02906202) is evaluating the efficacy and safety of autologous cell transplantation with LentiGlobin. Advanced gene-editing approaches aim to cut DNA at a targeted site and convert HbF to HbA during infancy, such as the suppression of BCL11A (B cell lymphoma 11A), HPFH (hereditary persistence of fetal hemoglobin) and zinc-finger nucleases. Gene therapy is progressing rapidly, with multiple clinical trials being conducted in many countries and the promise of commercial products to be available in the near future.

Serum ferritin levels and irregular use of iron chelators predict liver iron load in patients with major beta thalassemia: a cross-sectional study

AimTo determine whether serum ferritin, liver transaminases, and regularity and type of iron chelation protocol can be used to predict liver iron load as assessed by T2* magnetic resonance imaging (MRI) in patients with beta thalassemia major (TM).MethodsThis cross-sectional study, conducted from March 1, 2014 to March 1, 2015, involved 90 patients with beta TM on regular packed red blood cell transfusion. Liver and cardiac iron load were evaluated with T2* MRI. Compliance with iron-chelating agents, deferoxamine or deferasirox, and regularity of their use, as well as serum ferritin and liver transaminase levels were assessed.ResultsPatients with high serum ferritin were 2.068 times (95% confidence interval 1.26-3.37) more likely to have higher liver or cardiac iron load. High serum aspartate aminotransferases and irregular use of iron chelating agents, but not their type, predicted higher cardiac iron load. In a multiple regression model, serum ferritin level was the only significant predictor of liver and myocardial iron load.ConclusionsHigher serum ferritin strongly predicted the severity of cardiac and liver iron load. Irregular use of chelator drugs was associated with a higher risk of cardiac and liver iron load, regardless of the type of chelating agent.

A Pilot Optical Coherence Tomography Angiography Study on Superficial and Deep Capillary Plexus Foveal Avascular Zone in Patients With Beta-Thalassemia Major

To investigate foveal avascular zone (FAZ) changes in the superficial (SCP) and deep (DCP) capillary plexuses in beta-thalassemia major (BTM) patients, as shown in optical coherence tomography angiography. Nonrandomized, comparative case series of 54 eyes of 27 BTM patients and 46 eyes of 23 healthy controls, utilizing an automated FAZ detection algorithm. Measurements included FAZ area and FAZ shape descriptors (convexity, circularity, and contour temperature). Results were compared between the two groups, and correlated to iron load and chelation therapy parameters. SCP and DCP FAZ area were not significantly different between the control and BTM groups (P = 0.778 and P = 0.408, respectively). The same was true regarding SCP FAZ convexity (P = 0.946), circularity (P = 0.838), and contour temperature (P = 0.907). In contrast, a statistically significant difference was detected between controls and BTM group regarding DCP FAZ convexity (P = 0.013), circularity (P = 0.010), and contour temperature (P = 0.014). Desferrioxamine dosage was strongly correlated to the DCP area (r = 0.650, P = 0.05) and liver magnetic resonance imaging/T2-star to DCP circularity (r = -0.492, P = 0.038). Correlations were also revealed between urine Fe excretion and DCP convexity (r = 0.531, P = 0.019), circularity (r = 0.661, P = 0.002), and contour temperature (r = -0.591, P = 0.008). Retinal capillary plexuses and especially DCP seem to present unique morphologic changes in BTM patients, not in the FAZ area, but in specific shape descriptors, indicating minor but detectable FAZ changes. These changes correlate well with iron load and chelation therapy parameters. Their clinical importance and pathophysiologic implications remain to be elucidated through further studies.

Association of frequency of hereditary hemochromatosis (HFE) gene mutations (H63D and C282Y) with iron overload in beta-thalassemia major patients in Pakistan.

Objectives:To evaluate any association between the frequency of hereditary hemochromatosis (HFE) gene mutation (H63D and C282Y) and iron overload in beta-thalassemia major (BTM) patients.Methods:The case-control study was conducted from June 2016 to February 2018. Blood samples from 204 BTM patients and 204 normal controls were taken from the Sundas Foundation Blood Bank.These samples were analyzed for serum ferritin assay and HFE mutation. Ferritin level was measured on the ARCHITECT 1000SR. Both patient and control samples were analyzed for mutations using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP).Results:Serum ferritin levels for all patients were >1000ng/mL. The p.H63D mutation was observed in 23 (11.3%) cases, out of which 19 cases were heterozygous for p.H63D and 4 cases were homozygous. In control samples, 4 cases (2%) were found heterozygous for the p.H63D, and no homozygous mutation was found. Significantly high serum ferritin levels were found in BTM patients with the H63D mutation (p=0.00). In the case of p.C282Y, neither homozygous nor heterozygous mutation was found in patients or in controls.Conclusion:H63D polymorphism is associated with iron overload in BTM patients. Larger-scale research is required to give an elaborated view of the association of the HFE mutation with iron overload in these patients and to confirm our conclusion.

Molecular characteristics of thalassemia and hemoglobin variants in prenatal diagnosis program in northern Thailand.

Molecular analysis of globin genes is an essential process for prenatal diagnosis (PND) of severe thalassemia. This study aimed to describe the molecular characteristics of thalassemia and hemoglobin (Hb) variants in PND program in northern Thailand. The type and frequency of globin gene mutations from 1290 couples at risk of fetal severe thalassemia diseases that were tested at Thalassemia Laboratory at Chiang Mai University from 2012 to 2017 were retrospectively reviewed. The PND program detected 444 (34.4%), 196 (15.2%) and 642 (49.8%) couples at risk of fetal Hb Bart's hydrops fetalis, beta-thalassemia major (BTM) and beta-thalassemia/Hb E disease, respectively. Coinheritance of more than one type of thalassemia was common and eight (0.6%) couples were at risk of two types of severe thalassemia. There were two types of alpha0-thalassemia; 893 (99.7%) Southeast Asian and 3 (0.3%) Thai deletions. Twenty beta-globin gene mutations were found with 94.3% of beta0-thalassemia. The codon 41/42 (- TTCT), codon 17 (A>T), IVS-I-1 (G>T) and codon 71/72 (+ A) comprised 90% of beta-thalassemia mutations. The study shows a high percentage of couples at risk of fetal Hb Bart's hydrops fetalis and BTM. The percentage of beta0-thalassemia is higher than those seen in other regions of Thailand.

PB2399 BETA THALASSEMIA MINOR PATIENTS: NOT TIRED, BUT DEPRESSED AND ANXIOUS

Background:The quality of life has been influenced unfavourably and the prevalance of either depression or anxiety has been increased in beta thalassemia major (BTM) and beta thalassemia intermedia (BTI) patients. Yet, the studies including the quality of life in beta thalassemia minor (BTm) subjects are limited and just the depression was demonstrated to be frequent in individuals with BTm, compared to the healthy population. Likewise, the data regarding the presence of fatique and anxiety in adult BTm subjects is insufficientAims:We aimed to investigate whether the severity of fatigue and the incidences of depression and anxiety of patients with BTm are different than healthy individuals using Fatigue Severity Scale (FSS) and Hospital Anxiety and Depression Scale (HADS).Methods:Seventy‐seven BTm subjects were included in this study. The individuals (n = 38) using any medications, alcohol or tobacco; and having any chronic diseases and sleeping disturbances, were excluded. The remaining 39 BTm subjects were enrolled in the study. They had also normal biochemical parameters, thyroid function tests and C‐reactive protein (CRP). Twenty‐five healthy control subjects who were matched with age, sex, marital status, educational status and body mass index (BMI), were also included.Results:The BTm and the control groups were comparable in terms of gender, age, BMI, educational status and marital status (p = 0.368, 0.755, 0.851, 0.785, 0.709 respectively) (Table 1). Fatigue Severity Scale score was ≥4 in 23 (59.0%) BTm subjects and in 15 (60%) control subjects (p = 1.0). HADS anxiety score was ≥10 in 20 (51.3%) BTm subjects and in 5 (20.0%) control subjects (p = 0.018) and HADS depression score was ≥ 7 in 20 (51.3%) BTm subjects and 6 (24.0%) healthy control subjects (p = 0.039). There was no correlation of hemoglobin with FSS score (p = 0.526, r = ‐0.105), HADS anxiety score (p = 0.703, r = ‐0.063) or HADS depression score (p = 0.718, r = ‐0.06) in BTm group (Table 2).Summary/Conclusion:We found that both depression and anxiety were higher in BTm patients than healthy individuals, but this difference was not feasible for fatigue.imageimage

PS1574 HLA‐DRB1∗15 INCREASES THE RISK OF RED BLOOD CELLS ALLOANTIBODIES IN PATIENTS WITH BETA THALASSEMIA MAJOR

Background:The cornerstone of the management of Beta Thalassemia Major (B‐TM) is lifelong Red Blood Cells (RBC) transfusion. This is associated with the development of RBCs alloantibodies. Human Leukocyte Antigen (HLA) is considered a risk factor for a number of autoimmune disorders. We hypothesized that HLA impacts the rate of alloantibody formation in patients with B‐TM.Aims:To assess the impact of HLA alleles on the risk of RBC alloimmunization in patients with B‐TM.Methods:This is a retrospective cohort study of patients with B‐TM managed at Sultan Qaboos University Hospital (SQUH) between January 1996 till December 2016. All adult and paediatric patients with B‐TM with available HLA typing results were included. Patients with missing data were excluded. Chi‐squared test was used to assess the impact of HLA alleles on alloimmunization and the effect size was estimated using odd ratio (OR). HLA testing was performed using polymerase chain reaction – specific sequence of oligonucleotides (PCR‐SSO). Gel card technique (BIORAD ID‐System; DiaClon, Bio‐Rad, DiaMed GmbH, Switzerland) was used to screen for the RBC alloantibodies.Results:One hundred and sixty‐five patients fulfilled the inclusion criteria without missing information. The median age of all patients was 14 years. Females constituted 48% of the sample and 45% of patients were O RhD positive. The median RBC transfusion was 17 times per year. Patients were first detected to have RBC alloantibody at a median age of 16 years. The commonest RBC alloantibodies found in these patients were anti‐K (50%) and anti‐E (58%). The commonest HLA allele in loci A, B, C, DQ and DRB1 were HLA‐A∗02 (21%), HLA‐B∗51 (14%), HLA‐C∗7 (18%), HLA‐DQ∗05 (47%) and HLA‐DRB1∗16 (32%) respectively. HLA‐DRB1∗15 and HLA‐DQ∗6 were associated with a higher risk of RBC alloantibody formation (HLA‐DRB1∗15: OR 3.57, P = 0.047; HLA‐DQ∗06: OR 4.37, P = 0.025). None of the remaining common alleles (&gt;5%) in Omani population were associated with the risk of alloantibody formation (p values &gt;0.05).Summary/Conclusion:HLA‐DRB1∗15 and HLA‐DQ∗06 increases the risk of RBC alloantibody formation in patients with B‐TM. We recommend extended RBC phenotyping and extended antigen matched blood transfusion in patients carrying these two alleles. These findings will need to be confirmed in a larger multicenter study.

A 10-year longitudinal study of evaluation of ovarian reserve in women with transfusion-dependent beta thalassaemia major

ObjectiveAlthough spontaneous fertility and successful pregnancies have been reported in well-chelated and transfused women with beta thalassaemia major (BTM), majority of women are subfertile due to hypogonadotropic hypogonadism (HH). Little is known about the effect of iron overload on ovarian follicles and whether ovarian reserve is affected by the disease or treatment status. This study compares the markers of ovarian reserve in women with transfusion-dependent BTM over a period of ten years with healthy women from a control population. Study designWe performed a 10-year mixed (retrospective and prospective) longitudinal study in 17 women with transfusion-dependent BTM from our thalassaemia clinic between July 2007 to June 2017. The results were compared with 52 age-matched healthy women without any medical conditions (control population) attending our fertility clinic. Patient demographics, medical history, menstrual history, hormonal parameters (serum levels of FSH, estradiol, TSH and AMH) and antral follicle count were recorded in all women from both groups. Serum levels of ferritin, cardiac T2*, liver iron concentration, thyroid function (TSH) and liver function test results were also recorded at three different time points. ResultsSerum AMH levels, estradiol levels and antral follicle count were significantly lower in women with BTM compared with the control group (p < 0.05 for all). Low AMH levels were noted in both groups of women (with and without HH) with a background of BTM. Serum AMH levels positively correlated with AFC in women with BTM. ConclusionSerum AMH level and AFC were significantly lower in women with transfusion dependent BTM as compared to age-matched healthy controls suggesting a direct impact of the disease activity or iron overload on the ovary.

Occult hepatitis C virus infection in patients with beta-thalassemia major: Is it a neglected and unexplained phenomenon?

Occult hepatitis C virus (HCV) infection (OCI) is described as the presence of viral genome in both hepatocytes and peripheral blood mononuclear cells (PBMCs) despite constant negative results on serum HCV RNA tests. Beta-thalassemia major (BTM) describes a group of inherited blood diseases. Patients with BTM require repeated blood transfusions, increasing the risk of exposure to infectious agents. We aimed to assess the prevalence of OCI in Iranian BTM patients and to identify the role of host factors in OCI positivity. A total of 181 BTM patients with HCV negative markers were selected. HCV RNA was tested in PBMCs using nested polymerase chain reaction assay. The positive samples were then genotyped via restriction fragment-length polymorphism (RFLP) and 5'-untranslated region sequencing. Six (3.3%) out of 181 BTM patients had viral HCV genomes in PBMC samples. Three (50.0%), two (33.3%), and one (16.7%) out of these six patients were infected with HCV-1b, HCV-1a, and HCV-3a, respectively. OCI positivity was significantly associated with the serum level of uric acid (P = 0.045) and ABO blood group (P = 0.032). Also, OCI patients had unfavorable IFNL3 rs12979860 TT, IFNL3 rs8099917 GG, IFNL3 rs12980275 GG, and IFNL4 ss469415590 ∆G/∆G genotypes. In conclusion, we indicated the low frequency of OCI in BTM patients. Nevertheless, more attention is warranted considering the importance of this infection. Also, further studies are necessary to determine the actual prevalence of OCI among BTM patients in Iran.

Spectral domain optical coherence tomography findings in Turkish sickle-cell disease and beta thalassemia major patients

PurposeTo assess probable structural changes using spectral domain optical coherence tomography (SD-OCT) on sickle-cell disease (SCD) and beta thalassemia major (B-TM) patients, without any retinal abnormalities. MethodsThis cross-sectional study included 32 B-TM, 34 SCD patients, and 44 healthy controls. One of the eyes of all participants was evaluated for SD-OCT and choroidal thickness, retinal nerve fiber layer (RNFL) thickness, central macular thickness (CMT), ganglion cell complex (GCC). ResultsAge, gender, and intraocular pressure (IOP) were not statistically different between the three groups. Hemoglobin (Hgb), hematocrite (Htc), and ferritin levels were not statistically different between the SCD and B-TM groups. Choroidal thickness at the subfoveal region was statistically higher in the control group (353.79 ± 71.93) than in the B-TM (317.41 ± 53.44) and SCD (283.21 ± 63.27) groups. In addition, it was statistically higher in the B-TM group than the SCD group (P = 0.05). CMT did not differ among the three groups, average RNFL was only significantly thinner in SCD than in controls, and GCC thickness was significantly thinner in SCD than in controls and B-TM. ConclusionIn both diseases, we can show early structural changes even if proliferative or non-proliferative retinopathy or other ocular manifestations were not developed yet.

DUKUNGAN KELUARGA DALAM MERAWAT ANAK DENGAN THALASSEMIA BETA MAYOR

ABSTRAK&#x0D; Pendahuluan: Thalassemia merupakan penyakit anemia hemolitik yang diturunkan secara genetik. Indonesia termasuk salah satu Negara yang memiliki penduduk pembawa gena thalassemia dengan prevalensi sebesar 3-8%. Anak thalassemia beta mayor harus menjalani pengobatan dalam jangka waktu yang panjang sehingga memberikan dampak bagi anak dan keluarga. Penelitian ini bertujuan untuk mendapatkan gambaran tentang pengalaman keluarga dalam merawat anak dengan thalassemia beta mayor.&#x0D; Metode: Penelitian ini menggunakan pendekatan fenomenologi dan data dikumpulkan melalui wawancara mendalam terhadap 8 partisipan yang merupakan ibu sebagai caregiver utama dalam merawat anak dengan thalassemia beta mayor. Analisis data menggunakan metode Colaizzi.&#x0D; Hasil: Ditemukan 7 tema terkait pengalaman keluarga dalam merawat anak dengaan thalassemia, yaitu kemampuan keluarga merawat anak; respon negatif keluarga; tantangan dalam merawat anak; hambatan selama merawat anak; sumber dukungan bagi keluarga; upaya keluarga dalam menghadapi stresor; dan faktor-faktor yang mempengaruhi strategi koping.&#x0D; Kesimpulan: Sumber dukungan bagi keluarga selama merawat anak dengan thalassemia beta mayor didapatkan, baik dukungan dari internal dan eksternal dalam bentuk dukungan instrumental, emosional, informasi serta finansial.&#x0D; Kata Kunci: Dukungan Keluarga, Anak, Thalassemia

The Relationship between Serum Level of Ferritin and Cardiac Troponin T (cTnT) in Children with Major Beta-Thalassemia

Beta-thalassemia is one of the most common inherited blood disorder result from a defect in production of beta globin chain due to mutations in the HBB gene on chromosome 11, range from minor to sever transfusion dependent major beta-thalassemia. Major beta-thalassemia regarded as one of the major health problems in endemic regions as the Mediterranean basin, part of North and West Africa and South East Asia. Frequent blood transfusions cause progressive iron overload and hemochromatosis in the body which is the major complication of treatment lead to accumulation of iron in many organs and meanly in heart. The aim of the study is to determine the relation between serum ferritin and serum cTnT in children with major beta-thalassemia. A cross sectional study was carried out in Kirkuk City from 16th of January 2018 to 15th of March 2018. A total of 60 children with major Beta thalassemia admitted to thalassemia center in Azadi Teaching Hospital, and 30 non major Beta thalassemia children (control group) their age ranged between 2-10 years old, were investigated for s. cTnT and s. ferritin. There was a highly significant increase in s. ferritin level in children with major beta-thalassemia as compare with control of same age and gender. Also, There was a difference between the level of serum cTnT level in children with major beta thalassemia more than control, but not significant of same age and gender.

Study of the effect of different iron-chelating agents on early renal glomerular and tubular function markers in children with beta-thalassemia

Background Advances in the management of patients of beta-thalassemia major (BTM) and the advent of effective chelators have led to the discovery of many renal complications. Mechanisms of renal impairment in BTM are still not fully investigated. Chronic anemia and hypoxia, iron overload and its complications, and direct nephrotoxic effects of some chelators are the commonly used explanations. Objectives In this cross-sectional study, the aim was to investigate the prevalence of renal impairment in patients with BTM using some of both conventional and early markers of glomerular and tubular renal function and to investigate the relation between them and iron overload (s. ferritin) and the use of a specific chelator. Patients and methods The study included 60 transfusion-dependent patients with BTM without overt renal disease or risk factors, for example, diabetes mellitus, and 30 age-matched and sex-matched healthy children as a control group (group C). Patients were divided into two equal groups according to type of chelator: group A children receiving standard deferoxamine (DFO) and/or deferiprone and group B children receiving deferasirox (new treatment). Serum levels of ferritin, creatinine, and blood urea nitrogen; albumin/creatinine ratio (ACR) in urine; estimated glomerular filtration rate using Schwartz formula; urinary beta 2 microglobulin (UB2MG); and urinary calcium/creatinine ratio were measured in all patients and healthy control children. Results Serum creatinine was within the normal range in most of the patients, and no significant differences were found between the two thalassemic groups and the control group (P=0.473). ACR in urine and UB2MG were significantly higher in the two thalassemic groups, and the deferasirox group showed significantly higher levels than both DFO and/or deferiprone group and control group (P1=0.05 and P2=0.005, respectively, for ACR and P1=0.025 and P2=0.000, respectively, for UB2MG). UB2MG was abnormally high in 67 and 76% of the DFO and/or deferiprone group and deferasirox group, respectively, followed by microalbuminuria (16 and 30%, respectively). Glomerular hyperfiltration was prevalent, but there were no significant differences in the median of the three groups (P=0.766). Hypercalciuria was also prevalent in the two thalassemic groups with abnormally elevated urinary calcium/creatinine ratio in 30% of both groups but without significant differences in the median of the three groups (P=0.123). Serum ferritin was significantly positively correlated with ACR (P=0.002) and with UB2MG (P=0.000). Conclusions ACR can be used as an early marker of glomerular function. Deferasirox use is probably safe in the usual doses in low-risk patients, keeping into consideration that high doses of deferasirox cause disruption of the renal function.

A comparative study of temperamental, behavioral, and cognitive changes in thalassemia major, thalassemia minor, and normal population.

Background:Temperament in children and adolescents acts as a trait marker which can predict behavioral abnormalities. There was no systemic study in India which has compared the temperamental, behavioral and cognitive changes associated with this hemoglobinopathy among thalassemia major (TM) group.Materials and Methods:The specific objectives of this study were to find the clinicodemographic profile of individuals and parents, the behavioral, temperamental profile of children of beta TM and correlation of temperamental profile with number of blood transfusions, cognitive profile of children having beta TM, minor and age-matched control children and adolescents.Results:Child and adolescents having TM have more temperamental and behavioral problems (P < 0.001) and have more psychopathology in comparison to Tm group. Descriptive statistics of the groups and group comparison (ANOVA) shows statistically significant difference in Temperament Measurement Schedule (TMS) total, CPMS total, TMT A, TMT B, and Children's Depression Rating Scale (CDRS) scales (P = 0.000). Descriptive statistics and group comparison (Chi-square test) show significance in number of blood transfusions not with other parameters (P < 0.001). Comparison between TM (Case) and Tm (Control) (t-test) shows significance with only TMS total and CPMS scales, not in other scales. The correlation matrix showed significant correlation in-between all the parameters (blood transfusion, TMS, CPMS, TMT A, TMT B, and CDRS).Discussion:Those who have been diagnosed as TM have more behavioral and cognitive problems than their comparators. Youngsters receiving more blood transfusions due to their ailments scored higher in childhood depression rating scale.Conclusion:The temperamental, behavioural and cognitive profile are key determinants of both internalizing and externalizing symptoms and management plan can be guided accordingly as reflected in this study.

Menace of Hepatitis C virus among multitransfused thalassemia patients in Balasore district of Odisha state in India.

Context:Hepatitis C virus (HCV) is a potential cause of morbidity and mortality worldwide. It is most commonly transmitted through injecting drug use; the reuse or inadequate sterilization of medical equipment and the transfusion of unscreened blood products. Management of thalassemia requires long-term blood transfusion. Though it improves the overall survival, it carries a definite risk of infection which is expected to be higher in resource limited settings.Aims:To find the percentage of transfusion-transmitted infections (TTIs) in multitransfused patients of thalassemia in Eastern India.Settings and Design:The study was conducted to assess blood safety in rural population in India by measuring the percentage of TTIs including HCV in multitransfused thalassemia patients.Methods and Materials:One hundred and twenty three patients with major beta-thalassemia were enrolled in this study. The blood samples were tested using ELISA technique for all TTIs. HIV fourth generation kits, HbsAg, HCV third generation kits, malaria and syphilis, parbovirus IgM and parbovirus IgG kits, HEV Antigen and IgM antibody were used.Statistical Analysis Used:Proportions and means were calculated for categorical and continuous variables, respectively. Chi-square test was applied and P value of <0.05 was taken as significant.Results:The mean age of patients was 9.5 years ± 5.2 years. Among various TTIs, Hepatitis C and HIV was prevalent among 59.3% and 4.1% of the study participants, respectively.Conclusions:The causes of high prevalence of HCV may be due to donors being usually asymptomatic in early stages, despite being screened for HCV possibly due to missing early window period infections. The screening methodology of TTIs particularly HCV at the district and village level and consequent increased prevalence of HCV in multitransfused rustic population of India shows the extent of blood safety.