Long-term Blood Transfusion Research Articles

Concepts of MRI quantification of iron in the liver: present and future of modern multiparametric methods: a review

INTRODUCTION: Accumulation of excess iron in the body or systemic iron overload occurs for various reasons, mainly as a result of inherited disorders of iron regulatory pathways, long-term and/or regular blood transfusions, uncontrolled breakdown of hemoglobin in hemolytic anemias, hematological malignancies. Mild iron overload can be associated with chronic liver disease and metabolic syndrome (dysmetabolic iron overload).Despite optimal control of chelation, iron is deposition in vital organs such as the liver, heart, endocrine glands and subsequently damaged. Liver Iron Concentration (LIC) is linearly related to total body iron stores and may contain about 70% of the iron in the body. The introduction of MRI into the examination algorithm for patients with storage diseases provides the opportunity for early diagnosis of iron overload and monitoring the effectiveness of therapy.OBJECTIVE: To summarize the current state and prospects for the clinical use of MR methods for quantitative assessment of iron content in the liver.MATERIALS AND METHODS: An analysis of the main publications of domestic and foreign literature on non-invasive assessment of the degree of liver iron overload over the past 10 years was carried out in the main medical databases: Medline/PubMed, RISC/Elibrary, CyberLeninka, Google Scholar.RESULTS: It was revealed that the main methods of MRI noninvasive assessment of the iron content in the liver are SIR and R2* – relaxometry. The latter defines modern approaches to both qualitative and quantitative assessment of iron overload, providing a linear correlation with LIC. Information about diffuse changes in the parenchyma is important, since the presence of fat deposits in the liver can lead to an increase in R2*, therefore, a simultaneous quantitative determination of iron and fat deposits in the liver is completely rational.CONCLUSION: Diagnosis of liver iron overload is necessary to control and adjust the optimal treatment to prevent side effects of chelation therapy. To this end, the use of MRI has an enormous role, since the simultaneous acquisition of quantitative data on R2* and PDFF allows a comprehensive assessment of fat content and the degree of iron overload, which is not available to other imaging methods. The introduction of multiparametric liver MRI protocols with adaptation to new software will allow us to reach a new level of diagnosis of liver diseases.MRI is the main tool for visualization, quantification and identification of the risks of liver iron overload. Modern multiparametric MRI of the liver has promising clinical significance for the quantitative assessment of iron deficiency and the degree of steatosis in the complex diagnosis of diffuse liver diseases.

Sveobuhvatna analiza genotipova a-i b-talasemije i hematološki fenotipovi

Background: Guizhou Province is an area with high incidence of thalassemia. However, there are few large-sample studies on the correlation between genotypes and phenotypes in Guizhou Province. In this study, the phenotypes and genotypes of 1174 patients with thalassemia in Guizhou Province were collected, and the relationship between different genotypes and phenotypes was analyzed, providing a more accurate basis for genetic counseling, prevention and control of thalassemia. Methods: A total of 1174 patients with thalassemia were collected in Guizhou Provincial People's Hospital from October 2020 to December 2021 by PCR-reverse dot blot (RDB) hybridization assay, and their red blood cell (RBC), hemoglobin (Hb), mean erythrocyte volume (MCV), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC), red blood cell distribution width (RDW), hemoglobin (HbA), hemoglobin A2 (HbA2), and fetal hemoglobin (HbF) data were collected. The relationship between different genotypes and phenotypes was analyzed. Results: Among 1174 cases of thalassemia or carriers, there were 617 cases of a-thalassemia, 512 cases of b-thalassemia, 45 cases of coinheritance of aand b-tha-lassemia. The severity of anemia between a-thalassemia was positively correlated with the decrease of non-functional copy number of a-globin gene. The degree of anemia in non-deletion a-thalassemia was greater than that in deletion a-thalassemia. In b-thalassemia, b0 gene mutation did not produce b-globin, and b+ mutation expressed some bglobin, but it was lower than normal level. b0/b0 had no bglobin production, and long-term blood transfusion was required to maintain life. Compared with a-thalassemia, the degree of anemia in b-thalassemia whose clinical type was same as a-thalassemia was more serious. The anemia degree of coinheritance of aand b-thalassemia was less than that of simple a-thalassemia or b-thalassemia. Conclusions: The clinical phenotype of thalassemia is influenced by molecular mechanism, and the two kinds of thalassemia can interact with each other. The clinical severity is positively correlated with the imbalance of a peptide chain and b peptide chain. A comprehensive understanding of the hematologic phenotype differences between different genotypes and subtypes of thalassemia can provide more accurate data for genetic counseling of thalassemia.

Effective synthesis of fluorescent carbon dots and their application in controllable detection of deferasirox

As an iron chelation therapy, deferasirox (DEF) is commonly used as the primary treatment drug to prevent intracellular iron overload in patients with thalassemia who require long-term and large blood transfusions. However, due to the toxic side effects of long-term use, building a convenient and sensitive DEF detection method remains an important task. This study developed a simple and effective fluorescence detection strategy for DEF based on the coordination effect of DEF and Cu2+ (DEF-Cu). The high quantum yield N-doped blue emission carbon dots (CDs) synthesized by a simple one-step hydrothermal method were applied as the fluorescent probe. The DEF-Cu exhibited a new absorption peak centered at 334 nm, overlapping with the absorption wavelength of CDs, resulting in an internal filtration effect (IFE) for quenching the fluorescence of CDs. The quenching degrees of CDs caused by DEF-Cu showed a good linear relationship in the range of 0.5–20 μg/mL, with a detection limit (LOD) as low as 0.12 μg/mL. The accurate detections of DEF in dispersible tablets and plasma were also achieved. This strategy not only enriched the understanding of the properties of target drugs but also provided valuable insights for designing CDs with specific luminescent properties and applying them to distinctive methods for drug analysis.

Global and regional cardiac magnetic resonance feature tracking left ventricular strain analysis in assessing early myocardial disease in β thalassemia major patients

BackgroundCardiac magnetic resonance imaging (CMR) is the modality of choice for quantification of myocardial iron overload in β-thalassemia major patients using the T2* sequence. CMR feature tracking (FT) is a recent magnetic resonance imaging tool that gives an idea about myocardial fibers deformation; thus, it can detect early impairment in myocardial function even before the reduction in ejection fraction.MethodsThis study aims to assess the ability of left ventricular CMR-FT in the early detection of systolic dysfunction in β thalassemia major patients and to correlate it with the degree of myocardial iron overload measured by CMR T2*. This prospective study enrolled 57 β thalassemia major patients who received long-term blood transfusion and 20 healthy controls. CMR was used to evaluate left ventricular volumes, ejection fraction, and the amount of myocardial T2*. A two-dimensional left ventricular FT analysis was performed. Both global and segmental left ventricular strain values were obtained.ResultsThe mean global circumferential strain (GCS) and global radial strain (GRS) values were significantly lower in patients compared to control (P = 0.002 and P = 0.006, respectively). No correlation was found between T2* values and ejection fraction; however, there was a significant correlation between T2* values and GCS and GRS (P = 0.012 and P = 0.025, respectively) in thalassemia patients. Regional strain revealed significantly lower values of GCS and GRS in basal regions compared to apical ones (P = 0.000).ConclusionsOur study revealed that CMR-FT can play a role in the early detection of systolic impairment in thalassemia patients.

Advance of research on the role of BCL11A in the occurrence and treatment of β-Thalassemia

β-Thalassemia is a single-gene disease caused by mutations in β-globin and has a distinct geographical characteristics. Current treatment for patients with moderate to severe thalassemia has mainly relied on long-term blood transfusion and/or hematopoietic stem cell transplantation. B cell lymphoma/leukemia 11A (BCL11A) as a transcriptional repressor plays a vital role in monitoring γ/β hemoglobin switching, maintaining the normal function of hematopoietic stem cells, and regulating erythrocyte differentiation and lymphocyte development. With the rapid progress in gene editing technology, the BCL11A as a therapeutic target for β-thalassemia has shown promising results. This article has systematically summarized the regulatory mechanism and therapeutic potential of the BCL11A, with an aim to provide new ideas for the treatment of β-thalassemia.

Comparison of oral iron chelators in the management of transfusion-dependent β-thalassemia major based on serum ferritin and liver enzymes.

Excess iron deriving from a chronic transfusion and dietary intake increases the risk for cardiac complications in β-thalassemia major patients. Deferiprone and deferasirox are commonly prescribed to thalassemic patients who are at risk of iron overload. This study aimed to compare the performance and toxicity of deferiprone and deferasirox in β-thalassemia major patients. A cross-sectional observation was performed on 102 patients with β-thalassemia major. Serum ferritin along with total, indirect, and direct bilirubin levels were measured. Levels of liver enzymes, transaminase (ALT), and aspartate transaminase (AST), were also determined. Ferritin correlations with serum ALT, AST, and total bilirubin were constructed based on Spearman's rank correlation. Statistical differences based on the serum parameters were analyzed between deferiprone and deferasirox groups. The differences of iron chelators' effects between those receiving short-term (≤7 years) and long-term (>7 years) blood transfusion were also analyzed. The averaged levels of bilirubin, ALT, AST, and ferritin were found to be high. Ferritin was positively correlated with ALT (r=0.508 and p<0.001) and AST ((r=0.569; p<0.001). There was no statistical difference in ferritin levels between the deferiprone and deferasirox groups ( p=0.776). However, higher total bilirubin and ALT were observed in the deferasirox group than in the deferiprone group ( p=0.001 and 0.022, respectively). Total ( p<0.001), indirect ( p<0.001), and direct bilirubin levels ( p=0.015) were significantly higher in patients with long-term transfusions than those receiving short-term transfusions. Higher ferritin was found with a statistical significance of p=0.008 in the long-term transfusions group. Ferritin is high in people with transfusion-dependent β-thalassemia major and positively correlated with ALT and AST. Deferasirox might pose a higher risk of developing hepatic injury as compared with deferiprone. Yet, no significant change of deferasirox efficacy (based on ferritin level) was found between those receiving short-term and long-term transfusions.

Prevalence of Anti-HLA Antibodies in Multiply Transfused Patients with Hematologic Malignancy

Background: Human leukocyte antigen (HLA) alloimmunization can be induced by exposure to non-self HLA molecules, such as foreign tissue during transplantation, pregnancy, and blood products. Antibodies against HLA lead to serious complications in patients receiving blood transfusions. Objective: The present study aimed to determine the prevalence and risk factors for HLA alloimmunization in multiple transfused patients with hematologic malignancies at Siriraj Hospital. Materials and Methods: The present research was a cross-sectional study. The samples comprised 100 cases of hematologic malignancy patients who had a history of at least three episodes of transfusion with cellular blood components. All patients were tested for anti-HLA class I and class II antibodies by Luminex assay. Results: The overall prevalence of HLA alloimmunization in multiple transfused patients with hematologic malignancies was 40%. Anti-HLA class I, class II, and both class I and class II antibodies were detected in 35%, 30%, and 25% of the patients, respectively. Factors related to the development of anti-HLA antibodies were previous pregnancy (OR 4.82, 95% CI 1.62 to 14.35, p=0.005), five or more transfusions (OR 7.82, 95% CI 2.22 to 27.55, p=0.001), and diagnoses with myelodysplastic syndromes (MDS) antibodies (OR 5.88, 95% CI 1.98 to 17.47, p=0.001). Conclusion: Patients with hematologic malignancies who required long-term blood transfusion support could be at high risk for the development of anti-HLA antibodies. Important risk factors are pregnancy, multiple transfusions, and MDS. Keywords: HLA alloimmunization, Anti-HLA antibodies, Blood transfusions, Hematologic malignancy

CRISPR/Cas-based gene editing in therapeutic strategies for beta-thalassemia.

Beta-thalassemia (β-thalassemia) is an autosomal recessive disorder caused by point mutations, insertions, and deletions in the HBB gene cluster, resulting in the underproduction of β-globin chains. The most severe type may demonstrate complications including massive hepatosplenomegaly, bone deformities, and severe growth retardation in children. Treatments for β-thalassemia include blood transfusion, splenectomy, and allogeneic hematopoietic stem cell transplantation (HSCT). However, long-term blood transfusions require regular iron removal therapy. For allogeneic HSCT, human lymphocyte antigen (HLA)-matched donors are rarely available, and acute graft-versus-host disease (GVHD) may occur after the transplantation. Thus, these conventional treatments are facing significant challenges. In recent years, with the advent and advancement of CRISPR (clustered regularly interspaced short palindromic repeats)/Cas9 (CRISPR-associated protein 9) gene editing technology, precise genome editing has achieved encouraging successes in basic and clinical studies for treating various genetic disorders, including β-thalassemia. Target gene-edited autogeneic HSCT helps patients avoid graft rejection and GVHD, making it a promising curative therapy for transfusion-dependent β-thalassemia (TDT).In this review, we introduce the development and mechanisms of CRISPR/Cas9. Recent advances on feasible strategies of CRISPR/Cas9 targeting three globin genes (HBB, HBG, and HBA) and targeting cell selections for β-thalassemia therapy are highlighted. Current CRISPR-based clinical trials in the treatment of β-thalassemia are summarized, which are focused on γ-globin reactivation and fetal hemoglobin reproduction in hematopoietic stem cells. Lastly, the applications of other promising CRISPR-based technologies, such as base editing and prime editing, in treating β-thalassemia and the limitations of the CRISPR/Cas system in therapeutic applications are discussed.

Detecting rare thalassemia in children with anemia using third-generation sequencing

ABSTRACTBackgroundIn China, conventional genetic testing methods can only detect common thalassemia variants. Accurate detection of rare thalassemia is crucial for clinical diagnosis, especially for children that need long-term blood transfusion. This study aims to explore the application value of third-generation sequencing (TGS) in the diagnosis of rare thalassemia in children with anemia.MethodsWe enrolled 20 children with anemia, excluding from iron deficiency anemia (IDA). TGS was employed to identify both known and novel thalassemia genotypes, while sanger sequencing was used to confirm the novel mutation detected.ResultsAmong the 20 samples, we identified 5 cases of rare thalassemia. These included β−4.9 (hg38,Chr11:5226187-5231089) at HBB gene, α−91(HBA2:c.*91delT), αCD30(HBA2:c.91-93delGAG), Chinese Gγ+(Aγδβ)0(NG_000007.3: g .48795-127698 del 78904) and delta – 77(T > C)(HBD:c.-127T>C). Notably, the –SEA/α−91α genotype associated with severe non-deletional hemoglobin H disease (HbH disease) has not been previously reported. Patients with genotypes β654/β−4.9 and –SEA/α−91α necessitate long-term blood transfusions, and those with the –SEA/αCD30α, Chinese Gγ+(Aγδβ)0 and delta thalassemia demonstrate mild anemia.ConclusionsTGS demonstrates promising potential as a diagnostic tool for suspected cases of rare thalassemia in children, especially those suspected to have transfusion-dependent thalassemia (TDT).

The Role of Non-genetic Therapies to Reduce the Incidence of Sickle Cell Crisis: A Systematic Review.

Sickle cell anemia is a hemoglobinopathy that causes complications such as Vaso-Occlusive Crisis (VOC), stroke, priapism, Acute Chest Syndromes (ACS), and bone infarcts due to blood vessel occlusion, resulting in hypoxia, ischemia, and inflammation. Preventing these incidents improves the quality of life and lowers mortality rates in Sickle Cell Disease (SCD) patients. This systematic review aims to describe the drugs, their mechanisms of action, dosages, changes in hemoglobin parameters, decrease in VOCs, delay the time for the next VOC, decrease in the length of hospital stay, and side effects associated with these drugs. This review adheres to the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) 2020 guidelines. For this review, we searched the PubMed, Google Scholar, and Cochrane databases and screened them for full free texts published in English and studied in humans in the last five years beginning in 2018. Randomized clinical trials (RCT), observational studies, meta-analyses, systemic reviews, and traditional reviews were all included in the search. According to the type of study, quality assessment tools are used, and eight papers are chosen. Full-text articles from these papers are studied, analyzed, and tabulated. We discussed seven interventions that are used to treat sickle cell disease. Voxelotor, crizanlizumab, L-glutamate, long-term blood transfusions, Zinc (Zn), Niprisan®, and Ciklavit* were found to reduce the number and severity of VOC. We discovered that VOCs containing L -glutamate reduced the length of hospitalization. Magnesium (Mg) did not affect the number and severity of VOCs. This review includes a few articles for the study. Future papers on this subject should include a large sample size and many papers. More clinical trials are required to evaluate the dosages and outcomes of using these drugs in combination to prevent VOCs.

Evidence for the Metabolic Activation of Deferasirox In Vitro and In Vivo.

Deferasirox (DFS) is used for the treatment of iron accumulation caused by the need for long-term blood transfusions, such as thalassemia or other rare anemia. Liver injury due to exposure to DFS has been documented, and the toxic mechanisms of DFS are unknown. The present study aimed to investigate the reactive metabolites of DFS in vitro and in vivo to help us understand the mechanisms of DFS hepatotoxicity. Two hydroxylated metabolites (5-OH and 5'-OH) were identified during incubation of DFS-supplemented rat liver microsomes. Such microsomal incubations fortified with glutathione (GSH) or N-acetylcysteine (NAC) as capture agents offered two GSH conjugates and two NAC conjugates. These GSH conjugates and NAC conjugates were also detected in bile and urine of rats given DFS. CYP1A2 and CYP3A4 were found to dominate the metabolic activation of DFS. Administration of DFS induced decreased cell survival in cultured primary hepatocytes. Pretreatment with ketoconazole and 1-aminobenzotrizole made hepatocytes less susceptible to the cytotoxicity of DFS.

Comparison of oral iron chelators in the management of transfusion-dependent β-thalassemia major based on serum ferritin and liver enzymes

Background: Excess iron deriving from a chronic transfusion and dietary intake increases the risk for cardiac complications in β-thalassemia major patients. Deferiprone and deferasirox are commonly prescribed to thalassemic patients who are at risk of iron overload. This study aimed to compare the performance and toxicity of deferiprone and deferasirox in β-thalassemia major patients. Methods: A cross-sectional observation was performed on 102 patients with β-thalassemia major. Serum ferritin along with total, indirect, and direct bilirubin levels were measured. Levels of liver enzymes, transaminase (ALT), and aspartate transaminase (AST), were also determined. Ferritin correlations with serum ALT, AST, and total bilirubin were constructed based on Spearman’s rank correlation. Statistical differences based on the serum parameters were analyzed between deferiprone and deferasirox groups. The differences of iron chelators’ effects between those receiving short-term (≤7 years) and long-term (&gt;7 years) blood transfusion were also analyzed. Results: The averaged levels of bilirubin, ALT, AST, and ferritin were found to be high. Ferritin was positively correlated with ALT (r=0.508 and p&lt;0.001) and AST ((r=0.569; p&lt;0.001). There was no statistical difference in ferritin levels between the deferiprone and deferasirox groups (p=0.776). However, higher total bilirubin and ALT were observed in the deferasirox group than in the deferiprone group (p=0.001 and 0.022, respectively). Total (p&lt;0.001), indirect (p&lt;0.001), and direct bilirubin levels (p=0.015) were significantly higher in patients with long-term transfusions than those receiving short-term transfusions. Higher ferritin was found with a statistical significance of p=0.008 in the long-term transfusions group. Conclusions: Ferritin is high in people with transfusion-dependent β-thalassemia major and positively correlated with ALT and AST. Deferasirox might pose a higher risk of developing hepatic injury as compared with deferiprone. Yet, no significant change of deferasirox efficacy (based on ferritin level) was found between those receiving short-term and long-term transfusions.

Brain iron content and cognitive function in patients with β-thalassemia.

Patients with β-thalassemia (β-TM) may have brain iron overload from long-term blood transfusions, ineffective erythropoiesis, and increased intestinal iron absorption, leading to cognitive impairment. Brain magnetic resonance imaging (MRI) methods such as the transverse relaxation rate, susceptibility-weighted imaging, and quantitative susceptibility mapping can provide quantitative, in vivo measurements of brain iron. This review assessed these MRI methods for brain iron quantification and the measurements for cognitive function in patients with β-TM. We aimed to identify the neural correlates of cognitive impairment, which should help to evaluate therapies for improving cognition and quality of life in patients with β-TM.

KNOWLEDGE, ATTITUDE, AND PRACTICE TOWARDS VOLUNTARY BLOOD DONATION AND ASSOCIATE FACTORS AMONG KHULNA UNIVERSITY STUDENTS

Voluntary blood donation (VBD) is the foundation of blood safety and safe transfusion methods. It is vital to boost volunteer donor recruitment and retention to ensure a long-term safe blood transfusion practice, especially among university students. The goal was to evaluate Khulna University students' blood donation knowledge, attitude, and practice (KAP) as well as associated factors. A cross-sectional study was conducted at Khulna University in April 2022. Using simple random sampling (SRS), 400 face-to-face interviews were taken, of which 394 records were used for further analysis. A Chi-square test was used to check the association between KAP toward VBD, and binary logistic regression was applied to identify the association between explanatory and outcome variables. The logistic regression reveals that students with good knowledge about VBD are associated with permanent residence (OR: 1.651; 95% CI: 1.028, 2.650) and education (OR: 1.746; 95% CI: 1.012, 3.014). Favorable attitude toward VBD is associated with gender (OR: 1.818; 95% CI: 1.073, 3.079), division (OR: 3.058; 95% CI:1.241, 7.535) and social media time (OR: 0.068; 95% CI:0.001, 0.876). The practice of VBD is associated with gender (OR: 5.375; 95% CI:3.115, 9.273) and current residence (OR: 0.0397; 95% CI:0.181, 0.869). Efforts should be undertaken to use knowledge and a favorable attitude toward students at the Khulna university to accomplish the aim of 100% VBD in the future.

Stored whole blood transfusion initiates serum amyloid A activation monitored by real-time dynamic imaging.

Transfusion of stored whole blood (SWB) to resuscitate severe traumatic haemorrhage patients in military operations and civilian emergency centres is being increasingly used in routine practice. It has been well established that transfusion of red blood cells (RBCs) after prolonged storage has harmful effects, mainly mediated by inflammation. Whether the side effects of inflammation are brought about by SWB transfusion remains unclear. A hepatocyte SAA (serum amyloid A) specific reporter mouse that facilitated non-invasive imaging of hepatocyte SAA expression was used to evaluate acute inflammation and acute-phase reaction after the transfusion of SWB or components separated from end-storage whole blood. The whole blood of C57BL/6 donor mouse was used to model an allogeneic transfusion to BALB/c recipient mouse. End-storage whole blood (14 days of storage) transfusion induced the most significant SAA expression, while 10-day storage resulted in a much weaker signal compared to their fresh and 5-day storage counterparts. RBCs rather than white blood cells and plasma-containing platelets are thought to be responsible for the systemic inflammatory and SAA activation during end-storage whole blood transfusion. Circulatory and hepatic pro-inflammatory cytokines secreted by M1-polarised macrophage initiated the SAA expression in hepatocytes through nuclear transcription factor NF-κB. Storage lesions will also occur during the storage of whole blood, which is related to the change in RBCs with prolonged storage. The side effect induced by systemic inflammation and acute-phase reaction should be considered before resuscitation with long-term storage whole blood transfusion.

Prevalence of Hepatitis C Infection and its Genotypes in Suspected Hemodialysis Patients, Southwest of Iran

Background: Hemodialysis patients are more prone to Hepatitis C Virus (HCV) infection due to the need for long-term hemodialysis and blood transfusions. Objectives: The present study aimed to determine the HCV infection burden, viral load, and genotype pattern in hemodialysis patients referred to a research center from 2011 to 2018. Methods: Among 131 hemodialysis patients with suspected HCV infection, referred to Prof. Alborzi Clinical Microbiology Research Center, Shiraz, Iran, from 2011 to 2018, the HCV rate was assessed with the enzyme-linked immunosorbent assay and the HCV RNA load and genotypes by one-step TaqMan real-time PCR. Results: The prevalence of HCV-Ab positivity was 29% among hemodialysis patients, of whom 21 (57%) were HCV RNA-positive. In the rest of the hemodialysis patients who were HCV-Ab-negative, the HCV RNA was detected in five (12%) patients. Genotype 3 (Gt-3) was the most prevalent one detected in 50% of the patients whose genotypes were determined. Also, the HCV viral load in HCV-seropositive patients was generally higher than that in HCV-seronegative ones. Conclusions: This study showed that high HCV infection and different genotype patterns among hemodialysis patients compared to the general population are the main predictors of HCV infection, which indicates healthcare facility transmission because of inappropriate infection management practices.

Correlation Between Serum Ferritin and Testosterone Level in Adolescent Male with Transfusion Dependent Thalassemia

Transfusion-dependent thalassemia (TDT) is a type of beta-thalassemia that needs regular and long-term blood transfusions. Complications can occur due to the deposition of iron in TDT patients, including endocrine complications causing deficiency of testosterone that plays a role in the secondary sexual development in males. The objective of this study was to understand the correlation between ferritin and testosterone level in male adolescences with transfusion-dependent thalassemia. This cross-sectional observational correlative study was conducted from April to August 2019 on 74 males aged 12-18 years old who were presented to the Thalassemia Outpatient clinic, Dr. Hasan Sadikin General Hospital, Bandung. Blood was collected using phlebotomy for ferritin and total testosterone serum examination. Data were then analyzed using SPSS version 17.0. Low testosterone level (&lt;3.0 ng/mL) was found in 63.5% of subjects. Results of the Spearmen correlation test demonstrated a negative correlation with r: -0,699 and p-value &lt;0.001, showing a negative, strong, and significant correlation among those variables. The higher ferritin level in TDT patients indicates a high level of the free iron level in the body that can destroy the endocrine organs and cause deprivation of testosterone secretion, leading to hypogonadism in transfusion dependent thalassemia patients.

A Case Report: Infertility Treatment of a Female with Beta-thalassemia Major

Beta-thalassemia is caused by a genetically mediated deletion of beta-globin chain of hemoglobin. It is an autosomal recessive disease, which causes a severe medical condition that requires longterm blood transfusions. An impaired hypothalamic-pituitary-ovarian axis mainly causes infertility in such patients. This case report presents a 26-year-old female, a known case of beta-thalassemia major, that received monthly blood transfusions before conceiving. The patient sought consultation for the treatment of primary infertility at Bahrain Defence Force Royal Medical Services (BDF-RMS) Hospital. The patient underwent two trials of intrauterine insemination (IUI). The goal was to build up endometrial thickness by gonadotrophins administration for embryo implantation. To conclude, IUI combined with gonadotrophins for ovarian stimulation has shown success. Keywords: Artificial Insemination, Beta-Thalassemia, Hypogonadism, Infertility, Pregnancy

Deferasirox Adherence and Persistence Among Texas Medicaid Patients Taking Dispersible Tablets and Film-Coated Tablets

Background: Chronic iron overload is a significant complication associated with long-term blood transfusions required to treat patients with sickle cell disease, thalassemia, myelodysplastic syndromes, and other blood disorders. Without iron chelation therapy (ICT), which binds to and removes excess plasma iron, patients would experience iron accumulation in the body, leading to liver, heart, or other organ failure. Despite the seriousness of these complications, low adherence to ICT has been reported. Deferasirox (DFX) is a once-daily oral ICT with documented better adherence compared to parenteral deferoxamine. Before March 2015, DFX was available only as a dispersible tablet (DT) that must be mixed with liquid; however, in March 2015 the FDA approved a film-coated tablet (FCT) version of DFX. Improved adherence with DFX-FCT has been reported, but studies conducted in Medicaid populations are limited. This study investigated medication adherence and persistence between Texas Medicaid patients taking DFX-FCT and DFX-DT, and among patients who switched from DFX-DT to DFX-FCT.Objectives: (1) To compare medication adherence and persistence between Texas Medicaid patients taking DFX-DT and DFX-FCT; and (2) to evaluate adherence and persistence in patients who switched from DFX-DT to DFX-FCT.Methods: A retrospective analysis was conducted using 2014-2016 Texas Medicaid prescription claims data. For patients taking either DFX-DT or DFX-FCT, the index date was the date of the first DFX-DT or DFX-FCT claim between 4/1/2015 and 12/31/2015, and patients were followed for 12 months. For patients who switched from DFX-DT to DFX-FCT, the switch date was the date of the first DFX-FCT claim between 4/1/2015 and 12/31/2015. The study period was 12 months before and 12 months after the switch date. Included patients were 2-63 years of age at index/switch, and were continuously enrolled in Texas Medicaid.Adherence was measured using the medication possession ratio (MPR) and proportion of days covered (PDC). Persistence was defined as continued access to medication without a gap of >60 days. Mann-Whitney U/Wilcoxon Signed Rank and Chi-square/McNemar tests were used for continuous and categorical variables, respectively.Results: A total of 57 and 165 Texas Medicaid patients who met the study criteria were taking DFX-DT and DFX-FCT, respectively. MPR was not significantly different between patient groups; however, PDC was significantly greater for DFX-FCT patients (median = 0.66; mean +/- SD = 0.61 +/- 0.25) compared to DFX-DT patients (median = 0.49; mean +/- SD = 0.49 +/- 0.25; p=0.003). Nearly 30% of DFX-FCT patients were adherent (PDC >= 0.8), while 15.8% of DFX-DT patients were adherent (p=0.039). DFX-FCT patients had greater persistence over DFX-DT patients (p=0.021). Accordingly, a significantly greater proportion of DFX-FCT patients were persistent with their ICT compared to DFX-DT patients (47.3% vs. 28.1%; p=0.011).For 121 eligible patients who switched from DFX-DT to DFX-FCT, MPR was not significantly different between pre- and post-switch periods. However, median (mean +/- SD) PDC increased from 0.58 (0.55 +/- 0.24) when patients were taking DFX-DT to 0.66 (0.66 +/- 0.23) when they switched to DFX-FCT (p<0.001), and persistence significantly increased from 227.6 days to 263.3 days (p=0.008). When patients were taking DFX-DT during the pre-switch period, 24.0% and 35.5% were considered adherent and persistent, respectively; these proportions increased to 34.7% and 54.5%, respectively, when patients switched to DFX-FCT.Conclusions: In the Texas Medicaid population taking DFX, medication adherence and persistence is better with DFX-FCT compared to DFX-DT. To optimize patient health outcomes and use of resources, health care providers and decision-makers should be aware of adherence and persistence rates associated with ICT, and actively monitor and encourage ICT adherence among patients. DisclosuresRichards:Novartis: Research Funding. Lawson:Novartis: Research Funding. Said:Novartis: Employment. Sasane:Novartis: Employment.

Evaluation of glycemic abnormalities in children and adolescents with \u03b2-thalassemia major

BackgroundThe quality of life of B-thalassemia major (β-TM) patients has improved with the use of frequent blood transfusions. However, this leads to chronic iron overload with its sequelae, as prediabetes and diabetes mellitus. This study aimed to assess insulin resistance and glucose abnormalities in a sample of B-thalassemia major patients in Benha, Egypt.ResultsThis case-control study included 40 B-thalassemia major patients on regular blood transfusion and iron chelation. Their ages ranged from 8 to 16 years, and 30 normal age and sex-matched controls. Thorough clinical examination was performed including weight (kg), height (m), body mass index (BMI) (kg/m2), and liver and spleen size. Laboratory investigations were done in the form of complete blood count, liver enzymes, serum ferritin, fasting plasma insulin, and fasting, and 2 h postprandial plasma glucose. Insulin resistance (IR) was calculated using the Homeostasis Model Assessment of insulin resistance (HOMA-IR) index. Insulin resistance was found in 27.5% of thalassemic patients; 18.2% of them had diabetes, 72.7% were prediabetics (with impaired fasting glycemia), and 9.1% had normal fasting and 2 h postprandial plasma glucose level. Insulin resistance increased significantly with increased blood transfusion duration, serum ferritin, liver enzymes, fasting plasma insulin, fasting plasma glucose, and 2 h postprandial plasma glucose (ROC). The curve analysis showed that the duration of blood transfusion, serum ferritin, fasting plasma insulin, fasting, and 2 h postprandial plasma glucose could significantly predict insulin resistance at a certain cut-off point.ConclusionOur data show that HOMA-IR can be used to detect insulin resistance in β-TM patients on long-term blood transfusions, especially patients with high serum ferritin and impaired liver enzymes.