UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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.

BACKGROUND: When deferasirox is used in iron chelation therapy, maculopapular rash occurs in 10% of patients, but there is no accepted and implemented protocol for the management of these drug reactions in adults.
METHODS: A 23-year-old woman diagnosed with thalassemia major is presented. She had taken 1,500 mg oral deferasirox for 1 week. Five hours after the last dose, a pruritic maculopapular rash developed on the body, face, and hands. The rash spread to the whole body within 3 days. The absolute necessity for the patient to take the drug was clarified by the hematology department. The patient\'s history was evaluated. A delayed-type hypersensitivity reaction due to deferasirox was considered.
RESULTS: The slow desensitization protocol described in the literature and applied on a case-by-case basis in pediatric patients was modified to shorten the duration by determining appropriate doses for the current preparation. The desensitization process was started with 1/100,000 of the total dose and the therapeutic dose was reached with a 2- to 2.5-fold increase in dose. No pre-medication was applied. During the procedure, at a low dose of 0.1 mg, local flushing and erythema was observed around the auricle on the face. The reaction did not progress.
CONCLUSIONS: Slow desensitization protocol for oral deferasirox was successfully applied in an adult patient.

Deferasirox (DFS) is an oral iron chelator that is employed in retinal ailments as a neuroprotectant against retinal injury and thus has utility in treating disorders such as excitoneurotoxicity and age-related macular degeneration (AMD). However, the conventional oral route of administration can present several disadvantages, e.g., the need for more frequent dosing and the first-pass effect. Microneedles (MNs) are minimally invasive systems that can be employed for intrascleral drug delivery without pain and can advantageously replace intravitreal injections therapy (IVT) as well as conventional oral routes of delivery for DFS. In this study, DFS was formulated into a nanosuspension (NS) through wet media milling employing PVA as a stabilizer, which was successfully loaded into polymeric dissolving MNs. DFS exhibited a 4-fold increase in solubility in DFS-NS compared to that of pure DFS. Moreover, the DFS-NSs exhibited excellent short-term stability and enhanced thermal stability, as confirmed through thermogravimetric analysis (TGA) studies. The mechanical characterization of the DFS-NS loaded ocular microneedles (DFS-NS-OcMNs), revealed that the system was sufficiently strong for effective scleral penetration. Optical coherence tomography (OCT) images confirmed the insertion of 81.23 ± 7.35 % of the total height of the MN arrays into full-thickness porcine sclera. Scleral deposition studies revealed 64 % drug deposition after just 5 min of insertion from DFS-NS-loaded ocular microneedles (OcMNs), which was almost 5 times greater than the deposition from pure DFS-OcMNs. Furthermore, both DFS and DFS-NS-OcMN exhibited remarkable cell viability when evaluated on human retinal pigment (ARPE) cells, suggesting their safety and appropriateness for use in the human eye. Therefore, loading DFS-NS into novel MN devices is a promising technique for effectively delivering DFS to the posterior segment of the eye in a minimally invasive manner.

UNASSIGNED: Iron chelators; deferasirox, deferiprone, and deferoxamine; used to treat iron toxicities due to excessive ingestions or blood transfusions, may cause serious adverse reactions.
UNASSIGNED: This study investigates pharmacovigilance data to uncover unknown safety information. Disproportionality analysis was conducted using VigiBase, the WHO global database of individual case safety reports, to known safety profile of products and the FDA Adverse Event Reporting System, reviewing over 117.000 iron chelator cases between 2010 and 2020.
UNASSIGNED: Commonly reported adverse events for iron chelators are general disorders and administration site conditions and GI-related disorders. Reporting Odds Ratio was calculated for iron chelator associations to headache (common), blurred vision (rare) and sepsis (serious). Strong association between deferoxamine and blurred vision (ROR: 2.47 in VigiBase and 3.04 in FAERS), deferiprone and sepsis (ROR; 5.95 in VigiBase and 1.24 in FAERS) were identified. However, results showed some inconsistent associations, such as headache and deferiprone, blurred vision and deferasirox association as per FAERS data; sepsis and deferasirox and deferoxamine association as per VigiBase data. Forty-five new potential signals with different associative values were suggested.
UNASSIGNED: The study identified strong associations between specific iron chelators and adverse events, though some inconsistencies were observed in the data. These findings, including the 45 new potential signals, suggest areas for further review and validation with additional data.

OBJECTIVE: This study aimed to evaluate the knowledge, attitude, and practice toward iron chelating agents (ICAs) in Iranian thalassemia major patients.
METHODS: A total of 101 patients with thalassemia major were involved in this cross-sectional survey. A deep medication review was done, and participants\' knowledge, attitude, and practice were evaluated by a validated instrument based on a 20-scoring system.
RESULTS: Statistical analyses showed 52 patients (51.5%) had a poor knowledge level (scores < 10) about their medications, 37 (36.6%) had a moderate level (scores 10-15), and 12 (11.9%) had a satisfactory level (scores > 15). Seventy-seven (76.2%) patients have positive beliefs regarding the dependence of their current health status on taking iron chelators, and 63 (62.4%) believed that they would become very ill without taking medication. The results also showed that the mean practice score in patients who received deferoxamine was 5.81 ± 3.50; in the patients who received deferiprone and those who received deferasirox, the mean scores were 7.36 ± 5.15 and 14.94 ± 4.14. Also, the knowledge and practice level had a direct linear correlation based on the regression analyses (P < 0.001).
CONCLUSIONS: In conclusion, results of the present research suggests that the patients\' knowledge about the administration, adverse events, and necessity of ICAs was not satisfactory. Improving the knowledge of thalassemia patients toward their medicines through educational interventions is highly recommended to improve their practice level.

BACKGROUND: Hemoglobin disorders such as thalassemia major have created an economic burden on the health care system. Iron chelation therapy (ICT) is the most expensive cost component in patients with thalassemia. ICT was administered to reduce the toxic effects of iron overload. This study aims to compare the costs of iron chelators as monotherapy in patients with thalassemia major in Indonesia, specifically in Cipto Faculty of Medicine, Universit.
METHODS: This is a retrospective analytical observational study. Data were collected from the thalassemia registry from 2016 to 2019. Patients\' age, gender, type of thalassemia, and type of iron chelation were recorded. Complications and total annual costs were evaluated. All thalassemia patients aged ≥2 years who were only receiving monotherapy ICT and had no history of therapy switching were eligible. We excluded subjects who moved out to other facilities or lost to follow-up.
RESULTS: From a total of 256 subjects, 249 subjects were included. The median age is 28 years old. Both sexes were represented equally. As many as 96.8% of subjects have thalassemia beta. Deferiprone was the most common iron chelator used (86.7%). Complications were observed in the subjects based on 4-year data collection; most of them were cardiomyopathy, diabetes mellitus, delayed puberty, and malnutrition ( P =0.422; P =0.867; P =0.004; and P =0.125, respectively). Deferiprone had a lower mean annual cost of USD 3581 than deferasirox, which had a cost of USD 6004.
CONCLUSIONS: Cardiomyopathy, diabetes mellitus, delayed puberty, and malnutrition were the most common complications found in the study. This study showed that deferiprone should be taken as consideration as a drug of choice to treat iron overload in thalassemia provided by Indonesian national health insurance which is less costly despite the probability of complications found after the treatment was given. Further investigations are required to evaluate contributing factors of complications in thalassemia.

We conducted a retrospective cohort study on 663 transfusion-dependent β-thalassemia patients receiving the same iron chelation monotherapy with deferoxamine, deferiprone, or deferasirox for up to 10 years (median age 31.8 years, 49.9 % females). Patients on all three iron chelators had a steady and significant decline in serum ferritin over the 10 years (median deferoxamine: -170.7 ng/mL, P = 0.049, deferiprone: -236.7 ng/mL, P = 0.001; deferasirox: -323.7 ng/mL, P < 0.001) yet had no significant change in liver iron concentration or cardiac T2*; while noting that patients generally had low hepatic and cardiac iron levels at study start. Median absolute, relative, and normalized changes were generally comparable between the three iron chelators. Patients receiving deferasirox had the highest morbidity and mortality-free survival probability among the three chelators, although the difference was only statistically significant when compared with deferoxamine (P = 0.037). On multivariate Cox regression analysis, there was no significant association between iron chelator type and the composite outcome of morbidity or mortality. In a real-world setting, there is comparable long-term iron chelation effectiveness between the three available iron chelators for patients with mild-to-moderate iron overload.

Accumulation of iron in vital organs is increasingly challenging in clinical settings during the lifespan of thalassemia patients. Iron overload hurdle these organs to redox imbalances. Commonly used iron-chelating agents in (deferasirox and, deferoxamine) could have a positive antioxidant role. Therefore, the aim of this study was designed to compare the effects of deferasirox and, deferoxamine, iron-chelating agents in oxidative stress in patients with β-thalassemic major. In this case series comparative study, 60 known cases of β-thalassemic patients receiving chelating agents therapy were divided into two groups of thirty, group one consisted of 30 patients 16 male and14 female, who received oral agent deferasirox tablets at dose 20-40mg/kg. Group two consisted of 30 patients, 16 male and 14 female, on intravenous therapy with Deferoxamine at a dose of 20-50mg/kg, Another thirty healthy individuals matched with age and gender, were kept as a control group. Total antioxidant capacity (TAOC) and Malondialdehyde (MDA) were measured in all studied groups. The three groups were similar in terms of age, and gender, A statistically non-significant difference in age (p>0.05) existed between the control and patient groups (10.9±2.93; 11.2±4.1*;11.6±3.6*) respectively. The number of patients in to control group and male-to-female numbers were matched since the ratios were similar. A statistically non-significant difference in BMI (p>0.05) existed between the control and patient groups (17±2, 17.2±2, 18±2.4*) respectively. TAOC is lower in-patient groups, when compared with the control group (27.8 ± 10.7; 32.5 ± 10.2; and 79.5 ± 7 u/ml) respectively, while the MDA value is higher when compared with the control group (7.2±4.6 and, 6.6±4.42; and 0.57±0.26; nmol/ml) respectively. The TAOC in patients group on Deferoxamine, is higher, while MDA is lower than in patients on Defrasirox. The TAOC in patients was reduced and Oxidative stress was enhanced in patients with thalassemia. Deferoxamine is more effective in modulating redox status.

Recent studies showed that patients with iron overload had increased risk of insulin resistance or diabetes. Ferroptosis is a new type of cell death mainly caused by iron-dependent oxidative damage. In the present study, we investigated potential mechanisms of iron overload induced hepatic ferroptosis and insulin resistance through in vivo and in vitro experiments. In vivo, the mice models of iron overload were established by intraperitoneal injection of iron dextran. The changes of body weight, serum ferritin and blood glucose were measured. Hematoxylin-eosin (HE) and Perl\'s stainings were used to observe the pathological changes and iron deposition in the liver of mice. In vitro, HepG2 cells were treated with ferric ammonium citrate (FAC, 9 mmol/L, 24 h) to establish the cell models of iron overload. The labile iron pool, cell viability, glucose consumption and glycogen contents were measured. The ultrastructure of mitochondria was observed by transmission electron microscope (TEM). The malondialdehyde (MDA) and glutathione (GSH) kits were used to detect lipid peroxidation in liver tissues of mice and HepG2 cells. RT-PCR and Western blot were used to detect the mRNA and protein expression levels of ferroptosis factors and JAK2/STAT3 signaling pathway. In this study, we used the iron chelator deferasirox in mice and HepG2 cells. Iron overload caused weight loss, elevated serum ferritin, fasting blood glucose, fasting insulin, HOMA-IR, impaired glucose tolerance, and decreased insulin sensitivity in mice. HE staining and Perls staining showed clumps of iron deposition in the liver of iron overload mice. Iron overload could reduce the glucose consumption, increase MDA contents of HepG2 cells, while reduce glycogen and GSH contents in liver tissues of mice and HepG2 cells. TEM showed deletion of mitochondrial ridge and rupture of outer membrane in HepG2 cells with iron overload. Iron chelator deferasirox could significantly improve the above indicators, which might be related to the activation of JAK2/STAT3/SLC7A11 signaling pathway and hepatic ferroptosis. Iron overload could induce hepatic ferroptosis and insulin resistance by inhibiting the JAK2/STAT3/SLC7A11 signaling pathway, and the iron chelator deferasirox might improve hepatic insulin resistance induced by iron overload.

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