Repeated Blood Transfusions Research Articles

Prevalence of Hepatitis B and C in Patients of Thalassemia in Sargodha, Pakistan

Background: Thalassemia is one of the commonest genetic hematological disorders and a health issue of global concern. Because of repeated blood transfusions, ratio of hepatitis B and C positivity is escalating in these patients day by day who have further complicated the situation in the form of poor treatment outcomes and costs to individuals Aim: To measure the prevalence of hepatitis B and C among patients of thalassemia major in Sargodha, Pakistan. Study design: Cross-sectional study Place and duration of study: Rai Hospital & Hilal-e-Ahmar Hospital, Sargodha from 01-01-20221 to 31-12- 2021. Methodology: Three hundred and sixty thalassemia major patients, both beta and alpha, confirmed on hemoglobin electrophoresis admitted in the hospital were enrolled. Results: The mean age of the participants was 10.24±2.5 years, and 50% were male and 50% females. About 34% of the patients had hepatitis in which 30% had hepatitis C and 1.1% hepatitis B. 2.2% had both. Conclusion: Hepatitis b and C are highly prevalent among patients of thalassemia major. This also calls physicians, hematologists, pediatricians and policy makers to focus on counseling and support of thalassemia patients by providing them safe blood. Keywords: Prevalence, Hepatitis B and C, Thalassemia major, Blood transfusion

Myeloid Specific HO-1-SIRT1-p53 Nexus Protects Against Iron Induced Chronic Liver Injury in Sickle Cell Disease

Sickle cell disease (SCD) is an autosomal-recessive-genetic disorder that affects ~100,000 Americans and millions of people worldwide. People with SCD experience multiple complications, including acute pain episodes, stroke, and organ damage, with a median life expectancy of 42-47 years in the United States. Red blood cell transfusions are an important therapeutic intervention in SCD, however, chronically transfused SCD patients develop severe iron overload in the liver, heart, spleen, and endocrine organs with increased expression of inflammatory markers. In addition, there is evidence of abnormal iron metabolism in SCD with prior studies showing a low urinary hepcidin level in children with SCD and highly variable levels in adults. Thus, hepatic iron homeostasis in SCD both at baseline and upon repeated blood transfusion remains incompletely understood. In this study we evaluated iron homeostasis in Townes sickle cell mice at baseline and upon iron overload by iron dextran administration. We also evaluated the potential contribution of hepatic macrophages in hepatic iron homeostasis. Townes mice exhibited significant iron accumulation in the liver at baseline. We found significant reduction of hepcidin and increase in ferroportin and ferritin levels in the liver of sickle mice at baseline. However, upon hepatic iron overload (which was generated by intraperitoneal injections of iron dextran (1 g/kg) once a week for upto 10 weeks) the hepcidin ferroportin homeostasis was impaired and we found reduction of ferroportin and ferritin and increase in hepcidin in the sickle mouse liver. Immunohistochemically we could see a significant enrichment of iron loaded macrophages in the liver of SCD mice at baseline. Clodronate liposome mediated depletion of hepatic kupffer cells caused significant liver injury, hepatocyte death, systemic and hepatic iron accumulation and mortality in the mouse liver at baseline suggesting a protective role of hepatic kupffer cells in iron homeostasis. Mechanistic analysis further revealed protective mechanism through myeloid specific heme oxygenase 1 (HO-1)-sirtuin -1 (SIRT1)-p53 signaling that can potentially alleviate iron induced chronic liver injury in the SCD mice. At baseline, HO1 generated by kupffer cells stimulated SIRT1 activation in SCD mouse hepatocytes. Furthermore, HO-1 and SIRT1 prevented iron-induced senescence and hepatocyte cell death via regulating P53 signaling. Clodronate liposome-mediated kupffer cell loss drastically lowered HO-1 expression, which in turn reduced SIRT1 in SCD liver and accelerated senescence and cell death. In line with this finding, we also detected elevated levels of SIRT-1 in SCD patients’ blood serum. Work is currently underway to understand how modulation of HO-1-SIRT1-p53 signaling pathway can be used as a therapeutic option to combat iron induced chronic liver injury.

Prevalence and Specificities of Immune Red Cell Antibodies in Adult Patients with Sickle Cell Anaemia and Blood Donors in Uyo, South-South Nigeria: A Case-Control Study

Background: Sickle cell anaemia (SCA) is a major public health issue in Sub-Saharan Africa, including Nigeria. Transfusion of red blood cells is an essential therapeutic modality in SCA. Repeated RBC transfusions can cause alloimmunization resulting in haemolytic transfusion reactions, transfusion refractoriness among other complications. Aims and Objectives: The study aimed to determine the prevalence and specificities of immune erythrocyte alloantibodies among adult patients with SCA compared with healthy HbAA blood donors in Uyo, South-South Nigeria. Materials and Methods: All participants were interviewed using a structured questionnaire to obtain information on bio- data, blood transfusion history and other relevant SCA history. Antibody screening and identification were carried out using tube agglutination method with commercially made panel of cells. Results: A total of 160 subjects were studied. They were made up of 80 SCA patients and 80 healthy HbAA blood donors. Prevalence of red cell alloimmunization among multi-transfused patients with SCA was observed to be 11.3%. Alloantibodies identified were mainly against Rh antigens contributing 66.7% (anti-E 22.2%, anti-C 22.2%, anti-D 11.1% and anti-e 11.1%). Antibodies directed against Kell and Lutheran blood group antigens together constituted 33.3%. No antibody was detected in the controls. Advancing age (30 years and above) and ABO blood group were statistically associated with alloimmunization (P values of 0.043 and 0.013, respectively). Conclusion: Repeated blood transfusion is associated with the development of alloantibodies. Immunohaematologic tests in transfusion care of SCA patients should be improved to include extended red cell phenotyping and routine alloantibody screening and identification.

Rare Case of Epitheloid Angiosarcoma Posing a Diagnostic Challenge in Duodenal Biopsy

Abstract Introduction/Objective Angiosarcoma (AS) is an aggressive tumor usually arising in the skin and soft tissue. We report a unique case of AS presenting as multiple nodules in duodenum with epithelioid histomorphology without prior diagnosis. Methods/Case Report An 80-year-old man presented with dyspnea on exertion, fatigue and severe anemia. Initial work up showed bilateral pleural effusions; a wedge biopsy of the left lung was done, but results were inconclusive. The patient required repeated blood transfusions over the next three months due to persistent anemia, and gastroenterology was consulted to further investigate the cause of anemia. Occult blood was found on rectal examination. Endoscopy revealed multiple mucosal nodules and polyps in the duodenum. Biopsy showed sheets of markedly atypical, lamina propria infiltrating large epithelioid cells with vesicular nuclei, prominent nucleoli, and eosinophilic cytoplasm undermining an adenoma. The atypical cells showed strong positivity for vimentin, CD31 and ERG, patchy positivity for MNF 116; and negative for HHV-8, S-100, CK20, and various other markers. Ki-67 index was approximately 30%. The diagnosis of duodenal angiosarcoma was made and referred for expert consultation, who concurred with the diagnosis. The patient’s previous lung wedge biopsy was reviewed, and determined to represent small foci of metastatic epithelioid angiosarcoma. The patient received radiotherapy but remained dependent on frequent transfusions, and died 7 weeks after the duodenal biopsy. Results (if a Case Study enter NA) NA. Conclusion Angiosarcoma occurring in the GI tract is rare and has a poor prognosis. In our case, the patient presented with an occult GI bleed and was found to have metastatic disease on presentation. AS presenting with epithelioid morphology in the GI tract can cause significant diagnostic challenges; therefore, pathologist should be aware and may benefit from including vascular immunohistochemical markers in work up to rule out this clinically aggressive vascular malignancy.

Hematological Profile of Iron Overload in Rats Administered with Fruit Extract of Mahkota Dewa (Phaleria macrocarpa)

Background: Repeated blood transfusions lead to an accumulation of iron that exceeds the body's iron storage capacity. Free iron is able to catalyze the formation of hydroxyl radicals that cause oxidative damage and cell death. The use of iron chelating medicines for iron chelation therapy is limited by side effects. Mangiferin is a natural bioactive compound with iron chelating and antioxidant activity. Mahkota dewa is a plant native to Indonesia that contains mangiferin. Objectives: The aim of this study was to evaluate the effect of mahkota dewa fruit extract administration on hematological profile of iron overload rats. Material and Methods: Thirty rats were divided into 6 groups: normal rats (N), iron overload rats (IO), iron overload rats rats given deferiprone (D), mangiferin (M), Mahkota dewa fruit extract at a dose of 100 mg/kg BW (PM1), or 200 mg/kg BW (PM2). Rats were given injection of iron sucrose 15 mg every 3-4 days for 8 weeks. At week 8, rats were sacrificed. Hematological analysis was performed in this study. Results: Iron overload condition caused by iron sucrose injection did not cause statistically significant changes in the haematological profile. Likewise, the administration mahkota dewa fruit extract at a dose of 100 or 200 mg/kg BW did not cause changes in the hematological profile. Conclusions: The administration of mahkota dewa fruit extract did not alter hematological profile of iron oveload rats.

The properties and health hazards from early nuclear weapon fallout: The Castle Bravo incident revisited

Early fallout is defined as the fallback to the earth’s surface of radioactive particles shortly after a nuclear detonation (often arbitrarily defined within 24 h). At the difference of wide spreading global fallout, early fallout mainly consists of larger particles that are often visible. The initial mixture is rich in short- and very short-lived radionuclides associated with a very high initial activity that decreases rapidly (in 7 h, the dose rate is reduced by 90%). The main danger of early fallout results from external irradiation by highly penetrating gamma-radiation that may cause acute radiation sickness. Only in the case of the thyroid, internal irradiation by the incorporation of radioiodine may prevail. The bombings of Hiroshima and Nagasaki are examples of airbursts with many fatalities by prompt effects (blast, burns, and initial ionizing radiations), but they produced little fallout. The nuclear test code-named Castle Bravo on the Marshall Islands (1954) did not have casualties by its blast, thermal or initial radiation effects, but the inhabitants of the nearby islands and the crew of a Japanese fisherboat (Lucky Dragon) were affected by large amounts of fallout. For the inhabitants of the Rongelap Atoll, the average dose from external irradiation was assessed at 1.6 Gy. From a clinical point of view, based on hematological data using the METREPOL classification system, the acute radiation syndrome can be categorized as mild (H1). Blood transfusions were not required, and antibiotics were not administered for prophylaxis or therapy of infections related to irradiation. The equivalent dose received by the thyroid resulted mainly from internal irradiation with 7.6 Gy. The major late effects were thyroid abnormalities, including thyroid failure, nodules, and malignant tumors. The 23 Japanese crewmen seem to have been irradiated by higher doses (2.9 Gy). Compared to the hematological data of the Rongelap victims, the evolution pattern over time is quite similar. Still, the absolute values of the cell counts are lower, and on average, the acute radiation syndrome can be categorized as rather moderate (H2). Considering the individual cases, data show a large interindividual variability, and the clinical severity category ranges from “no alterations” (H0) to severe (H3). Victims were treated with repeated blood transfusions and antibiotics. Several of them developed jaundice, and one of them died six months after the incident showing symptoms compatible with subacute liver failure. A radiochemical organ analysis revealed that only the bones were clearly contaminated with fission products. In the 1990s, many surviving crewmen were diagnosed with hepatitis C, incurred probably from blood transfusions that were often contaminated at the time, and died from hepatocellular carcinomas. Thyroid dysfunctions were not reported. The Castle Bravo case permits to study the health hazards resulting from early fallout independently from the prompt effects of a nuclear detonation. The prevailing external irradiation was confirmed, except for the thyroid with a higher dose resulting from radioiodine incorporation mainly caused by ingestion. As shown for the Japanese fishermen, the risks incurred by medical treatments must be carefully weighed against the benefits of the therapeutic intervention. The cause of death of the only short-term fatality is not fully elucidated, but is consistent with liver failure due to transfusion hepatitis rather than radiation effects.

PULMONARY FUNCTION TESTS IN CHILDREN WITH BETA THALASSEMIA AND ITS CORRELATION WITH IRON OVERLOAD

Iron overload is the principal determinant of major complications in conditions requiring repeated blood transfusions, like Beta Thalassemia Major and Sickle Cell Anemia. Although pulmonary dysfunction is not the most signicant clinical manifestation of thalassemias, or indeed does not produce any symptoms, a certain reduction of pulmonary volumes has been reported to occur in most subjects with beta thalassemia receiving regular blood transfusions. This study was done to assess the pulmonary function of such patients by Spirometry and the type of pulmonary dysfunction and to study its co-relation with iron overload. A total of 54 patients with Beta Thalassemia major on regular blood transfusions, of ages 6 years and above, were made to undergo Pulmonary Function Tests, of which 21 (38.89%) were females and 33 (61.11%) were males. Serum Ferritin values were recorded in all patients as a measure of iron overload. Pulmonary dysfunction was observed in 42 (77.78%) patients.`A predominantly restrictive pattern was found in 38 (90.48%) patients. An obstructive pattern was found in 4 (9.52%) patients. Patients with an FEV1/FVC ratio of less than 70% of the predicted value were labeled as having obstructive pulmonary dysfunction. Patients with FVC values of less than 80% of the predicted value and a FEV1/FVC ratio of more than 80 percent of th6e predicted value were labeled as having restrictive pulmonary dysfunction . Among patients with restrictive dysfunction, those having FVC values between 70-79%, 50-69% and 35 to 49% were graded as having mild, moderate and severe restrictive dysfunction respectively. Among subjects with obstructive dysfunction, those having FEV1/FVC ratio values between 70-79%, 50-69% and 35-49% were graded as having mild, moderate and severe obstructive dysfunction respectively. The number of patients with mild, moderate and severe pulmonary dysfunction were 13 (30.95%), 25 (59.52%) and 4 (9.52%) respectively. The mean ferritin value was calculated for each category of severity to see if any kind of correlation exists between pulmonary dysfunction and iron overload. Pulmonary dysfunction was found in a signicant majority of the patients, however no signicant correlation was found between severity of pulmonary dysfunction and iron overload.

Efficiency and Safety of Desferioxamine Chelation Therapy in Paediatric Patients with Transfusion-Dependent Anaemia: Experience of two Centres from Sudan

Background: Repeated blood transfusion is the main therapeutic option for transfusion-dependent anaemias with consequent iron overload and organ damage .Therefore iron chelating agents are important protective measures for these patients. The aim of this study was to investigate the efficiency and safety of Desferroxamine in paediatrics population subjected to iron overload as a consequence of repeated transfusion in a group of Sudanese children Subjects & Methods: This was a descriptive cross-sectional hospital based study. Conducted in two main paediatric reference hospitals in, Sudan. Within the period between November 2017 and April 2018 (6 months duration). The two centres were JaafarI bn- Oaf hospital and Albulk hospital. The study population included all patients of transfusion dependent anaemia who received desferrioxamine within the study period. Hundred patients were enrolled in the study. The study variables were demographic data, number of blood transfusions , serum ferritin pre and post blood transfusion and treatment of desferrioxamin Results: Sixty percent (60%) of the studied cases were males and 40% were females ,46% were thalassemic, 46% were sicklers, 5% aplastic anemia and 3% with red cell aplasia .The mean serum ferritin level before starting desferoxamine was 2.14 and after dessferoxamine was 2.48, P –value was highly significant. The most common side effect encountered was skin rash (36%) Conclusion: This study revealed some features of safety and efficiency of desferoxamine therapy in Sudanese paediatrics population affected by transfusion-dependent anemia. More studies are needed to describe this important health problem

Burden estimation of hepatitis B & C in thalassemia patients in MGM Medical College and Hospital, Jamshedpur

Introduction: Thalassemia encompasses a group of genetic blood disorders, in which there is altered or inadequate haemoglobin synthesis and requires a repeated blood transfusion. Due to repeated blood transfusion, these patients are vulnerable to HCV, HBV, and HIV like blood transfusion transmitted diseases. Aims and Objective: To determine the prevalence of HCV and HBV infections in multitransfused thalassemia patients in a tertiary care hospital. Material And Methods: Cross sectional and observational studywas done on a total of 110 beta thalassemia patients aged between 2-25years &were categorised into four groups (2-7 years, group 1; 8-13 years, group 2; 14-19 years, group 3 and 20-25 years, group 4).For testing, 5 ml Blood sample was collected, Serum separatedand subjected to testing for HBsAg, and antibody to Hepatitis C, by ELISA method. Screening was done by immunochromatography test (point of care test). Results: A total of 110 patients of beta thalassemia major were included in our study. Out of this, 68(62%) were males and 42(38%) were females.

Do Endocrinopathies Differ in Most Prevalent Hemoglobinopathy of Middle East: Beta-thalassemia?

Repeated blood transfusions in thalassemia patients is followed by endocrinopathies as diabetes, hypothyroidism, hypogonadism, hypoparathyroidism, and disorders in calcium and vitamin D homeostasis. The aimof this study was to evaluate the association of beta-thalassemia patientsendocrinopathies and osteoporosis. Serum level of some factors related tothe function of gonads, thyroid, adrenal, and pancreas along with serumlevels of calcium, phosphate, albumin, vitamin D, and iron were measured.Bone marrow density was tested via dual-energy x-ray absorptiometry(DXA densitometry). In this study, 56 patients with major thalassemia wereinvestigated. Paraclinical analysis indicated osteopenia in 17 (30.4%) andosteoporosis in 39 patients (69.6%) in addition to other types of endocrinedisorders, such as hypogonadism in 29 (51.8%), hypothyroidism in 13(23.2%), hypoparathyroidism in 1 (1.8%), hypocortisolism in 2 (3.6%), anddiabetes in 9 (16.1%) patients. Endocrinopathies had no significant relationship with osteoporosis and osteopenia in men. However, hypogonadismhad a significant relationship with osteoporosis and osteopenia in womenwith thalassemia. Estradiol level was lower in women with osteoporosisin comparison with women with osteopenia. Ferritin levels had neitherassociation with osteoporosis nor with LH levels (P>0.05). Secondary hypogonadism disorders are the main causes of osteoporosis and osteopeniain female beta-thalassemia patients.

Blood transfusion in haematology: A qualitative exploration of patients' and healthcare professionals' perceptions.

Repeated blood transfusions are indicated for the management of patients with cancer or blood disorders. Patients' perceptions about transfusions may be associated with decision-making and coping, which has been under-explored in the haematology context. This study therefore aimed to explore haematology transfusion patients' and HCPs' perceptions of blood transfusion, drawing on theory and previously identified themes of transfusion perceptions. Semi-structured interview study with 14 adult blood transfusion patients and 14 HCPs (consultants, registrars, nurses) at two UK haematology units. Patient- and HCP-tailored topic guides were developed based on themes of blood transfusion perceptions identified in a systematic review: 'Health benefits', 'Safety/risk', 'Negative emotions', 'Alternatives' 'Decision making' and 'Necessity'. Transcripts were analysed using deductive and thematic analysis. Patient and HCP themes were compared using triangulation methods. Conceptual models (one for patients, one for HCPs) specific to haematology portraying the association between themes were developed. Findings for patients and HCPs converged with transfusion reported as beneficial for patients, who were largely involved in the decision-making. Both groups also reported concerns about transfusion, including iron-overload, allergic reactions and challenges to deliver transfusions in time-pressurized services. Themes in the conceptual models included patient 'Burden' of receiving repeated transfusions and 'Supportive relationships', reflective of patients' positive interactions with other patients and HCPs in the haematology unit. Despite the challenges for patients receiving repeated transfusions, convergent perceptions suggest a shared understanding of patients' transfusion experiences. Identified challenges could inform ways to improve transfusion services and patients' experiences.

Surrogate measures of insulin secretion and sensitivity (IS) in young children with beta thalassemia major on repeated blood transfusion and iron chelation therapy.

Surrogate measures of insulin secretion and sensitivity (IS) in young children with beta thalassemia major on repeated blood transfusion and iron chelation therapy.

Role of Iron in Aging Related Diseases.

Iron progressively accumulates with age and can be further exacerbated by dietary iron intake, genetic factors, and repeated blood transfusions. While iron plays a vital role in various physiological processes within the human body, its accumulation contributes to cellular aging in several species. In its free form, iron can initiate the formation of free radicals at a cellular level and contribute to systemic disorders. This is most evident in high iron conditions such as hereditary hemochromatosis, when accumulation of iron contributes to the development of arthritis, cirrhosis, or cardiomyopathy. A growing body of research has further identified iron’s contributory effects in neurodegenerative diseases, ocular disorders, cancer, diabetes, endocrine dysfunction, and cardiovascular diseases. Reducing iron levels by repeated phlebotomy, iron chelation, and dietary restriction are the common therapeutic considerations to prevent iron toxicity. Chelators such as deferoxamine, deferiprone, and deferasirox have become the standard of care in managing iron overload conditions with other potential applications in cancer and cardiotoxicity. In certain animal models, drugs with iron chelating ability have been found to promote health and even extend lifespan. As we further explore the role of iron in the aging process, iron chelators will likely play an increasingly important role in our health.

Cutaneous hyperpigmentation as a diagnostic marker of vitamin B12 deficiency: a case report

<p>Cutaneous hyperpigmentation and glossitis are recognized but often overlooked early signs of vitamin B12 deficiency (VB12D). Pernicious anaemia is the most common cause of VB12D. Many clinicians miss the diagnosis of this potentially fatal but treatable condition in the absence of the more often reported life-threatening neuropsychiatric and haematologic features, notwithstanding the concomitant presence of characteristic cutaneous signs. These apperceptions of conspicuous and early dermatologic signs lead to diagnostic delay, which can result in dire consequences for the patient. We report the case of a 24-year-old young woman who for two years had repeated blood transfusions, iron supplementation and haematinics on account of anaemia of undetermined aetiology of a yet to be determined aetiology, despite the simultaneous presence of a constellation of glaring dermatologic clues to vitamin B12 deficiency. Following diagnosis and the institution of the appropriate therapy, the patient made remarkable improvement with a reversal of pigmentation and correction of the anaemia within a month. She continues to see the haematologists for follow-up.</p>

Talasemi Major Hastalarında Tp-E Intervali Ve Tp-E/Qt, Tp-E/Qtc Oranlarının Değerlendirilmesi

Aim: Thalassemia major (TM) is a genetic hemoglobinopathy that causes chronic hemolytic anemia. Repeated blood transfusions are needed for treatment. Iron accumulation is used to predict the risk of ventricular arrhythmia. We designed this study to compare the Tp-e interval, Tp-e/QT ratio and Tp-e/QTc ratio, which are the novel and reliable predictors that show ventricular repolarization, between the TM patients and healthy control group.Method: We included 97 TM patients who presented to our outpatient clinic for routine cardiac check-up from March 2019 to June 2020 and 90 healthy volunteers. In addition to the demographic and echocardiographic findings, patients’ electrocardiograms (ECG) were retrospectively analyzed. Their serum ferritin, C reactive protein (CRP) levels and neutrophil to lymphocyte ratios were recorded and compared.Result: The Tp-e interval was 80 msn (60.0-80.0) in the group of thalassemia major patients whereas it was 60 msn (50.0-70.0) (p<0.001) in the control group. The Tp-e/QT ratio was 0.200 (0.160-0.225) in the TM group while it was 0.175(0.150-0.210) in the control group (p=0.014). The Tp-e/QTc ratio was 0.180 (0.130-0.190) in the TM group while it was 0.150 (0.130-0.180) in the control group (p=0.035). No correlation was found between their serum ferritin levels and ECG parameters.Conclusion: Prolonged Tp-e interval, Tp-e/QT ve Tp-e/QTc ratios on the ECG in TM patients are associated with impaired ventricular repolarization due to excessive cardiac iron deposition and ventricular arrhythmias. These simple but reliable parameters can be used to predict the risk of arrhythmia.

Comparative efficacy, safety, and cost of iron chelation monotherapy vs. combination therapy in pediatric beta-thalassemia major: a single-center retrospective study

Background Iron chelation therapy is used to maintain iron balance in β-thalassemia major patients who undergo repeated blood transfusions.
 Objective To compare the efficacy, safety, and cost of iron chelation combination regimens [deferiprone (DFP) + deferoxamine (DFO) or DFP + deferasirox (DFX])] vs. high-dose DFP monotherapy (≥ 90 mg/kg/day) in pediatric β-thalassemia major patients.
 Methods This cross-sectional, retrospective study was done at Cipto Mangunkusumo Hospital, Jakarta, Indonesia. Retrospective data was obtained from electronic medical records of pediatric b-thalassemia major patients with serum ferritin of ≥ 2,500 ng/mL and/or transferrin saturation of ≥ 60%, who received either combination or monotherapy iron chelation agents. Outcome effectiveness was determined by the reduction of serum ferritin level of at least 80%. Safety was analyzed descriptively. A pharmacoeconomic analysis was performed based on clinical outcomes consisting of effectiveness and direct medical costs.
 Results At the end of the study, serum ferritin was reduced in 34.7% of the combination therapy group and 27.5% of the monotherapy group, however there was no significant difference between the two treatments (P=0.391). Nine (19.5%) patients on combination therapy and 17 (21.2%) patients on monotherapy had adverse drug reaction (ADR), with the most frequently reported ADR was elevated transaminase enzyme levels. Cost minimization analysis revealed that monotherapy for 6 months was IDR 13,556,592.64 less expensive than combination therapy (IDR 44,498,732.07); whereas monotherapy for 12 months was IDR 20,162,836.10 less expensive than combination therapy (IDR 78,877,661.12).
 Conclusion Combination regimens are as effective as monotherapy regimens in reducing serum ferritin in pediatric β-thalassemia major patients. There is no differences of ADR between combination or monotherapy. The average cost per patient is less expensive with monotherapy compared to combination therapy.

Potential Use of Patient-Specific Induced Pluripotent Stem Cell for Liver Fibrosis Thalassemia Treatment Management

Thalassemia is the most common inherited single gene blood disease worldwide and present a significant health problem in the world. Approximately, 1.5% of the global populations (An estimated 80–90 million people) are carriers of β-thalassemia. Around 5% of Indonesia population is thought to carry the thalassemia gene. The globin imbalance in β-thalassemia major causes hemolysis and ineffective erythropoiesis which results in anemia leading to increases of iron absorption. Furthermore, repeated blood transfusion and long-term increased iron absorption will lead to excessive accumulation of iron in vital organs, especially in the liver, causes liver fibrosis then leading to liver disease. Iron overload can be controlled by iron chelating drugs with the risk of side effects; therefore, a breakthrough is needed. Stem cell technology has a potential to provide novel insight in thalassemia major, through induced pluripotent stem cells (iPSCs) who has the ability to differentiate into hepatic stellate cells (HSCs)-like cells. iPSCs derived HSC-like cells (iPSC-HSCs) present the phenotypic and functional characteristics of HSCs. The utilization of iPSCs is a new option in personalized thalassemia management.

IRON OVERLOAD CARDIOMYOPATHY IN THALASSEMIA MAJOR :A CASE REPORT

BACKGROUND: Cardiomyopathy is a major cause of morbidity and mortality in patients with thalassemia .Repeated blood transfusions leads to iron overload culminating in heart failure & death CASE PRESENTATION:A 16 year old boy known case of β-thalassemia major on multiple blood transfusions and iron chelation therapy presented to emergency with features of congestive cardiac failure, predominantly of right heart failure with pedal edema and ascites .on evaluation Transthoracic echocardiography showed dilated cardiomyopathy and raised cardiac enzymes .patient was started on guideline directed management for heart failure along with iron chelation therapy CONCLUSION: This is a case of β- thalassemia major with severe iron overload leading to dilated cardiomyopathy presenting with congestive cardiac failure.

Iron overload cardiomyopathy: Using the latest evidence to inform future applications.

Iron overload can be the result of either dysregulated iron metabolism in the case of hereditary hemochromatosis or repeated blood transfusions in the case of secondary hemochromatosis (e.g. in β-thalassemia and sickle cell anemia patients). Under iron overload conditions, transferrin (Tf) saturation leads to an increase in non-Tf bound iron which can result in the generation of reactive oxygen species (ROS). These excess ROS can damage cellular components, resulting in the dysfunction of vital organs including iron overload cardiomyopathy (IOC). Multiple studies have demonstrated that L-type and T-type calcium channels are the main routes for iron uptake in the heart, and that calcium channel blockers, given either individually or in combination with standard iron chelators, confer cardioprotective effects under iron overload conditions. Treatment with antioxidants may also provide therapeutic benefits. Interestingly, recent studies have suggested that mitochondrial dynamics and regulated cell death (RCD) pathways are potential targets for pharmacological interventions against iron-induced cardiomyocyte injury. In this review, the potential therapeutic roles of iron chelators, antioxidants, iron uptake/metabolism modulators, mitochondrial dynamics modulators, and inhibitors of RCD pathways in IOC are summarized and discussed.

Relationship between Oxidative Stress and the Blood Iron Concentration and Antioxidant Status in Major ß-thalassemia in Iraq.

Reduction or total lack of beta-globin chains caused by a congenital disease called ß-thalassemia major is one of the lives threatening diseases. Patients who suffer from ß-thalassemia need a repeated blood transfusion for survival. The repeated blood transfusion in ß-thalassemia patients may cause oxidative stress and tissue injury due to iron overload, altered antioxidant enzymes, and other essential trace element levels. The current study aimed to investigate the correlation of oxidative stress with serum trace element levels and antioxidant enzyme status in ß-thalassemia major patients. A total of 130 serum samples were obtained from ß-thalassemia major patients (n=100; 50 males and 50 females) and healthy individuals (n=30; 15 males and 15 females). Hematological parameters were measured on both groups by a comprehensive blood test that included the amount of hemoglobin Hb, packed cells volume, number of red blood cells, mean corpuscular volume ratio, mean corpuscular hemoglobin ratio, mean corpuscular hemoglobin concentration, red cell distribution width, white blood cells, and platelets counts. All of these blood parameters showed a clear decrease in thalassemia patients, except for red blood cells and platelets counts, which demonstrated a significant increase. The highest significant mean for iron in males and females were 233.768 and 219.150 µgm\dL in patients, respectively, while the mean level of iron significantly reduced in the control group (113.40 and 103.33 µgm\dL in males and females, respectively). The results indicated a significant decrease in uric acid in males and females in the patient group (41.042 and 40.582 mg\L in males and females, respectively), compared to the control group (53.866 and 43.60 mg\L in males and females, respectively). Allantoin concentration was detected by high-performance liquid chromatography technique, the results of which showed that the highest values in patients were 62.822 and 25.480 mg\L in males and females, respectively, compared to the control group 2.342 and 1.481 mg\L in males and females, respectively. Superoxide dismutase concentration decreased in patients (129.635 and 111.848 U\mL in males and females, respectively), compared to the control group (208.623 and 190.413 U\ml in males and females, respectively).