Deferoxamine Infusion Research Articles

Abstract WP122: Effect Of Prior Exposure To Statin Therapy On Clinical And Radiological Features Of Intracerebral Hemorrhage: A Post-hoc Analysis Of The I-def Trial

Background: Conflicting data exist regarding the relationship between prior statin use and perihematomal edema (PHE) in patients with intracerebral hemorrhage (ICH). We performed a post-hoc analysis of the ICH Deferoxamine (i-DEF) trial to examine whether there is an association between statin use prior to the onset of ICH and baseline PHE volume and its growth on 72-96 hour follow-up scans. Methods: Statin use prior to the study enrollment was assessed, and CT scans were performed at presentation and after 24 hours after the completion of a 3-day infusion of either saline or deferoxamine (DFO). ICH volumes and various PHE parameters were measured semi-quantititavely using Analyze imaging software. Multivariable logistic regression model was created, adjusting for the variables that were significantly different on univariable analyses, to assess for any associations between prior statin use and measures of ICH and PHE. Bonferroni correction was applied for multiple testing. Results: Seventy-four (25.4%) of 291 participants in i-DEF used statin prior to ICH onset. On univariable analyses, those with prior statin use had higher prevalences of hypertension, diabetes, and prior ischemic stroke, as well as concomitant antihypertensive and antiplatelet uses. Patients with prior statin use had smaller baseline ICH volume, absolute PHE (aPHE) volume, and edema extension distance (EED). Greater hematoma volume growth, baseline relative PHE (rPHE) volume, and reduction in rPHE volume from baseline to follow-up scans were also seen in those with prior statin use. On multivariable analysis, none of the measures of ICH and PHE was significantly associated with prior statin use, after adjusting for multiple testing. Conclusion: In this post-hoc analysis of a randomized controlled trial with standardized imaging and functional assessments, we did not find significant associations between pre-ICH statin use and measures of ICH or PHE volumes and their growth.

S120: RANDOMIZED CONTROLLED TRIAL OF THE EFFICACY AND SAFETY OF DEFERIPRONE: SUBGROUP ANALYSIS OF PEDIATRIC PATIENTS IN IRON-OVERLOADED PATIENTS WITH SICKLE CELL DISEASE AND OTHER ANEMIAS

Background: Children with sickle cell disease (SCD) managed with blood transfusions often require iron chelation therapy to prevent iron overload.1 Deferoxamine (DFO) is an iron chelator approved for pediatrics that is often infused; however, adherence is a key challenge due to the burdensome route of administration.2 Deferiprone (DFP), an oral iron chelator, is a first-line treatment for transfusional iron overload in children and adults with SCD and other anemias.3 DFP is noninferior to DFO in SCD with iron overload (evaluated by liver iron concentration [LIC]) and has an acceptable safety profile.4 This subgroup analysis of FIRST (NCT02041299) assessed whether efficacy and safety of DFP were comparable to DFO in children with SCD. Methods: In this phase 4 open-label study, patients were randomized 2:1 to DFP or DFO for 12 months. The subgroup analysis included children (2–16 years of age) with SCD or another rare anemia treated for transfusional iron overload. Children received either oral DFP three times a day or subcutaneous DFO infusion 5–7 days a week. Iron load was monitored and dosage adjustments were allowed. The primary endpoint was change in LIC from baseline to month 12. Data were analyzed for all patients with a baseline and a follow-up LIC assessment (efficacy population). Safety assessments were done for all patients who received at least 1 dose of study drug (safety population). All patients provided informed consent or assent. Results: Of 228 patients in the safety population, 128 (DFP, n=86; DFO, n=42) were children. Most children (DFP, 75.6%; DFO, 80.9%) had a primary diagnosis of SCD (HbS). Mean ages (SD) in the DFP and DFO groups were 9.9 (3.7) and 10.9 (3.0) years (P=0.09), respectively. There were no significant differences between the DFP and DFO groups in sex (males, 59.3% vs 57.1%; P=0.85), ethnicity (P=0.68), or race (P=0.34). 5 children withdrew due to AEs (all DFP) and 19 withdrew for other reasons (DFP, n=14; DFO, n=5). There was not a significant difference in number of withdraws between groups (P=0.23). Children treated with DFP or DFO showed no significant differences in overall incidence of AEs (P=0.77; including neutropenias [P=0.30]), severe AEs (P=0.10), serious AEs (P=0.16), or withdrawals due to AEs (P=0.17). A difference in overall incidence of nonserious AEs considered at least possibly related to DFP (59.3% vs 33.3%; P=0.01) was found. For AEs ≥5%: see Table 1. The only AE with a significantly higher rate with DFP vs DFO was elevated liver enzymes (P=0.03)—a known transient reaction to DFP typically resolving with continued DFP. There were no AEs observed with DFP that had not been previously reported. One child developed agranulocytosis during parvovirus infection, which resolved the following day; and children <6 years of age receiving DFP had a comparable safety profile to older children (6–16 years of age) receiving DFP. In the efficacy population, after 12 months, there was no significant difference in mean (SD) LIC change from baseline with DFP vs DFO (-3.39±4.24 mg/g vs -2.99±3.16 mg/g, respectively; P=0.57). Conclusions: This subgroup analysis of children receiving chronic transfusions for SCD or other anemias corroborates previous findings that DFP is comparable to DFO in reducing LIC. No new safety concerns were observed. These findings may benefit children and healthcare providers when considering effective iron chelation therapy that may also address treatment-adherence concerns.

Non-suicidal intentional ingestion of iron tablets and severe intoxication: the result of adolescent boy’s impulsive risky behaviour in the school

Acute iron poisoning is a potentially fatal intoxication in children. As the Iron preparations are commonly administered to pregnant women, lactating mothers, toddlers, it is easily available at home. So younger children are prone to consume it accidently. Although iron is a therapeutic drug in recommended dosages, excessive iron in the free state can produce toxicity by affecting multiple cellular processes by catalysing redox reactions with lipid peroxidation and free radical formation. The severity of intoxication depends on the amount of elemental iron ingested. Serious toxicity is usually associated with a dose of &gt;40 mg/kg of elemental iron. Levels more than 100 mg/kg are almost always fatal. We report a case where a 12-year male child intentionally taken 60 tablets of iron (ferrous fumarate) at his school as a part of competition or bet to other schoolmate and presented with acute iron poisoning with hepatic encephalopathy to us. Important initial laboratory parameters were AST-4,879 U/L, Prothrombin time-60 sec and Iron level-213 microgram/dl. With timely specific management i.e., deferoxamine infusion along with all required intensive care supportive management in PICU the patient was discharged successfully. We chose to report this case to highlight the risky behaviour of adolescence who usually grows physically and emotionally earlier but their prefrontal lobes are yet immature to take proper and correct decision. Thus, impulse activity may prove fatal for them.

Successful treatment with continuous infusion of deferoxamine for an aplastic anemia patient suffering from transfusion dependence

Successful treatment with continuous infusion of deferoxamine for an aplastic anemia patient suffering from transfusion dependence

Lung injury induced by short-term mechanical ventilation with hyperoxia and its mitigation by deferoxamine in rats

BackgroundLong-term mechanical ventilation with hyperoxia can induce lung injury. General anesthesia is associated with a very high incidence of hyperoxaemia, despite it usually lasts for a relatively short period of time. It remains unclear whether short-term mechanical ventilation with hyperoxia has an adverse impact on or cause injury to the lungs. The present study aimed to assess whether short-term mechanical ventilation with hyperoxia may cause lung injury in rats and whether deferoxamine (DFO), a ferrous ion chelator, could mitigate such injury to the lungs and explore the possible mechanism.MethodsTwenty-four SD rats were randomly divided into 3 groups (n = 8/group): mechanical ventilated with normoxia group (MV group, FiO2 = 21%), with hyperoxia group (HMV group, FiO2 = 90%), or with hyperoxia + DFO group (HMV + DFO group, FiO2 = 90%). Mechanical ventilation under different oxygen concentrations was given for 4 h, and ECG was monitored. The HMV + DFO group received continuous intravenous infusion of DFO at 50 mg•kg− 1•h− 1, while the MV and HMV groups received an equal volume of normal saline. Carotid artery cannulation was carried out to monitor the blood gas parameters under mechanical ventilation for 2 and 4 h, respectively, and the PaO2/FiO2 ratio was calculated. After 4 h ventilation, the right anterior lobe of the lung and bronchoalveolar lavage fluid from the right lung was sampled for pathological and biochemical assays.ResultsPaO2 in the HMV and HMV + DFO groups were significantly higher, but the PaO2/FiO2 ratio were significantly lower than those of the MV group (all p < 0.01), while PaO2 and PaO2/FiO2 ratio between HMV + DFO and HMV groups did not differ significantly. The lung pathological scores and the wet-to-dry weight ratio (W/D) in the HMV and HMV + DFO groups were significantly higher than those of the MV group, but the lung pathological score and the W/D ratio were reduced by DFO (p < 0.05, HMV + DFO vs. HMV). Biochemically, HMV resulted in significant reductions in Surfactant protein C (SP-C), Surfactant protein D (SP-D), and Glutathion reductase (GR) levels and elevation of xanthine oxidase (XOD) in both the Bronchoalveolar lavage fluid and the lung tissue homogenate, and all these changes were prevented or significantly reverted by DFO.ConclusionsMechanical ventilation with hyperoxia for 4 h induced oxidative injury of the lungs, accompanied by a dramatic reduction in the concentrations of SP-C and SP-D. DFO could mitigate such injury by lowering XOD activity and elevating GR activity.

Combined chelation with high-dose deferiprone and deferoxamine to improve survival and restore cardiac function effectively in patients with transfusion-dependent thalassemia presenting severe cardiac complications.

Iron overload-induced cardiomyopathy is the leading cause of death in patients with transfusion-dependent thalassemia (TDT). The mortality is extremely high in these patients with severe cardiac complications, and how to rescue them remains a challenge. It is reasonable to use combined chelation with deferiprone (L1) and deferoxamine (DFO) because of their shuttle and synergistic effects on iron chelation. Here, seven consecutive patients with TDT who had severe cardiac complications between 2002 and 2019 and received combined chelation therapy with oral high-dose L1 (100mg/kg/day) and continuous 24-h DFO infusion (50mg/kg/day) in our hospital were reported. Survival for eight consecutive patients receiving DFO monotherapy for their severe cardiac complications between 1984 and 2001 was compared. We found that combined chelation therapy with high-dose L1 and DFO was efficient to improve survival and cardiac function in patients with TDT presenting severe cardiac complications. Reversal of arrhythmia to sinus rhythm was noted in all patients. Their 1-month follow-up left ventricular ejection fraction increased significantly (P < 0.001). There were no deaths, and all patients were discharged from hospital with good quality of life. In contrast, all the eight patients receiving DFO monotherapy died (P < 0.001). Accordingly, combined chelation therapy with high-dose L1 and DFO should be considered in patients with TDT presenting cardiac complications.

2333 Acute Iron Toxicity in an Adult: Intentional or Accidental?

INTRODUCTION: In adults, iron overdose is usually associated with suicide attempts. Unfortunately, a majority of acute iron toxicity cases are fatal given the rapid progression to multi-organ failure. Literature on management of acute iron toxicity is scant with most of current available information reported in pediatric population. Here in, we report a case of acute iron toxicity in an adult. CASE DESCRIPTION/METHODS: A 58-year-old African American woman with a history of depression, prior suicide attempt and post-traumatic stress disorder presented to the emergency room with a 3-day history of coffee-ground emesis and abdominal pain. She was found to be hypotensive (74/45 mm Hg), and tachycardic (124 beats per minute). Laboratory investigation revealed a markedly elevated AST/ALT at 10518/5430 IU/L, alkaline phosphatase 260 IU/L, direct bilirubin 2.9 mg/dL, total bilirubin 4.9 mg/dL, INR 1.47, PT 16.8 sec, sodium 127 mmol/L, bicarbonate 14 mmol/L, BUN 45 mg/dL, Cr 5.92 mg/dL, anion gap 29 and lactate of 3.1 mmol/L. Additional comprehensive workup for acute liver injury was negative. She was fluid resuscitated with 5 liters of 0.9% normal saline. CT abdomen and pelvis with contrast revealed multiple radiopaque objects in the proximal ileum. Serum iron level was &gt;500, iron saturation &gt;273, TIBC 183, Transferrin 131 and Ferritin level of 867. She was started on a deferoxamine infusion at 5 mg/kg/hour and whole bowel irrigation with Colyte at 200 cc/hour. She was also started on continuous venovenous hemofiltration (CVVH) for anuric acute kidney injury. Deferoxamine was discontinued 24 hours after initiation, as her urine was clear and iron level was less than 350. Colyte was discontinued once stool output was clear. Her hospital course was complicated by small bowel obstruction, which resolved with bowel rest and non-operative supportive care. Psychiatry was consulted for a suicide risk assessment however, patient consistently denied any suicide attempt and collateral information from family was reassuring. The idea of accidental ingestion was entertained, however, the patient denied being on iron supplementation. Her iron levels, LFTs, and urine output were back to baseline 1-week post-discharge. DISCUSSION: Acute iron toxicity in adults can rapidly progressive to multiorgan failure and death. Deferoxamine should be initiated early in severe cases. Clinicians should be aware of other adjunctive measures like WBI and CVVH; they should be employed early in the treatment course to improve survival outcomes.

Efficacy of High Dose and Short Course of Deferoxamine Infusion on Cardiac Remodeling 0f Children with Thalassemia Major

Background: Speckle tracking echocardiography has great value in evaluation of regional and global myocardial function. Objectives: The goal of this study was an assessment of cardiac function and remodeling in children with thalassemia major after infusion of a high dose of deferoxamine during a short course by speckle echocardiography and evaluate the efficacy of this imaging modalities in the early recognition of recovering of myocardial dysfunction. Methods: In a prospective study between Feb 2014 till 2017 conventional 2 dimensional and speckle tracking echocardiography were done consecutively on 21 patients with beta-thalassemia major before intravenous infusion of high dose of deferoxamine (50 mg/kg) for 5 days and then after 3 months echocardiographic measurements repeated for assessment of efficacy of deferoxamine infusion on ventricular function and cardiac remodeling of our study population. Results: Serum ferritin of all patients reduced significantly (P < 0.001). Ejection fraction was improved after the therapy (P < 0.001). Mitral E/A velocity ratio after therapy increased significantly (P < 0.001). Strain imaging measures showed an increase in apical lateral, mid-lateral, basal lateral, mid-septal, basal septal left ventricular longitudinal wall strain three months after the use of high dose deferoxamine (P < 0.001). Apico-septal wall strain measurements of the left ventricle did not change significantly after high dose deferoxamine (P = 0.144). Conclusions: Intravenous infusion of high dose of deferoxamine after chelating of iron results in reduction of serum ferritin which may cause washout of cardiac deposit of iron with consequent improvement of cardiac function and remodeling.

Non‐transferrin‐bound iron and oxidative stress during allogeneic hemopoietic stem cell transplantation in patients with or without iron overload

Non‐transferrin‐bound iron and oxidative stress during allogeneic hemopoietic stem cell transplantation in patients with or without iron overload

Effect of intravenous Deferoxamine concomitant use with blood transfusion on serum ferritin in thalassemia major patients

Background: Subcutaneous Deferoxamineis often not tolerated by patients and its rejection leads to iron overload with its complications. So, other methods with better toleration and reduction of Deferoxamine consumption are necessary. The present study aimed to evaluate the effect of intravenous Deferoxamine infusion during blood transfusion on serum ferritin (SF) in thalassemia major patients.Methods: In a retrospective cross-sectional study, thirty four patients with β-thalassemia major treated with monthly blood transfusion at Bu-Ali hospital in Ardabil city from April 2013 to April 2014, were selected and followed for six months. The mean SF rate and the needed subcutaneous Deferoxamine rates before intervention were considered as baseline. All patients received intravenous Deferoxamine concomitant with their routine monthly blood transfusion for six months. After six months mean values for ferritin, subcutaneous Deferoxamine were compared with baseline values. Collected data were analyzed using t-test and paired t-test by SPSS, version 18.P&lt;0.05 was considered as significant.Results: Compared with baseline, the subcutaneous Deferoxamine rate and ferritin level have been decreased significantly after intervention.Conclusions: Intravenous Deferoxamine concomitant use with routine monthly blood transfusion in thalassemia major patients can lead to decreasing of ferritin level. With this method, patient care could be improved, health care costs and complications of treatment effectively reduced.

A Randomised 1 Year Study Evaluating the Impact of Vitamin C Supplementation on Systemic Iron Parameters of Iron Overload in Thalassemia Major Patients on Long-Term Treatment with Deferasirox

BackgroundAscorbic acid (AA) supplementation has traditionally been used in iron overloaded patients as means to increase iron chelation efficacy and replenish AA oxidized by labile iron found in those patients. The rationale leaned on AA's ability to render stored iron accessible to chelation, as found in urinary iron excretion following deferoxamine infusion. However, as AA increases labile iron redox-cycling and ensuing toxicity, we set to assess the long term benefits versus toxicity risks of the combined chelator-AA treatment.ObjectivesPerform a prospective, open-label, randomized and controlled 1 year study on thalassemia patients treated with deferasirox (DFX) in order to assess the effects of AA supplementation on: a. markers of systemic iron overload in selected organs and in plasma and b. markers of plasma labile iron (LPI) as potential contributors to oxidative stress toxicity.Patients and MethodsEnrolment: 22 beta thalassemia major (TM) patients ≥10 years treated >2 years with DFX. Exclusion: cardiac dysfunction/arrhythmia or mT2* MRI <6 ms. Study: patients previously unexposed to AA received once-daily DFX (up to 40 mg/kg/d) with or without 125 mg AA for 1 year. All parameters were measured at baseline (BL); serum ferritin (SF) monthly, liver iron (LIC by MRI) and cardiac iron (mT2*MRI) after 1y. e-LPI (surrogate NTBI marker) and LPI (plasma redox-active labile iron marker) were assessed at BL, mo 1 & 6 by FeROS™ (Aferrix, Ltd) and fasting plasma AA at BL and EOS (fluorimetrically). Blood samples were withdrawn on the morning of transfusion day, 24 hours after last DFX (+/- AA) administration. Safety was followed using laboratory and clinical tests. AA levels were also determined in 23 healthy individuals (age and gender matched).Results22 TM patients were enrolled (mean age 23.5, range 10-34 y). The average dose ± SD of DFX given to all 22 patients was 38±4.5 mg/kg/d. 11 patients were randomised to receive DFX and the others with DFX supplemented with 125 mg AA (mean 2.4±0.5, range 1.9-4.2 mg/kg) for 1 year.At BL, the AA levels were significantly lower in the TM group compared to controls (2.44 ± 3.38 vs 9.60± 4.36 mg/dl respectively, p<0.000001). 11 of 22 patients had AA levels >-2SD of control group whereas the other 11 patients showed normal ranges of AA. The AA deficient patients were those that showed significantly higher SF, LIC and lower mT2* at BL (Table 1).In the DFX+AA arm, 5/11 (45%) patients had subnormal AA levels at BL but attained normal status after 1 year, as did all others on AA. Of the 5/11 (45%) DFX-treated patients that did not receive AA had normal BL AA and only 2/11 maintained normal AA status at EOS.A significant correlation was obtained between BL SF, LIC and mT2* and e-LPI (r 0.49, p 0.025; r 0.57, p 0.01; r -0.43, p 0.057 respectively) but not with LPI. The changes associated with DFX alone or with AA from BL to EOS were subtle for all parameters measured (Table 2).Importantly, eLPI and LPI remained at basal levels throughout 6 months treatment in both arms. With DFX alone, LPI were 0.34±0.30 units (mM iron) (BL) & 0.63±0.58 (6 mo); eLPI: 1.71±1.93 at BL & 2.48±3.11 (6 mo). DFX+AA: LPI were 0.33±0.46 (BL) & 0.35±0.44 (6 mo); eLPI: 2.13±1.71 (BL) & 1.78±1.51 (6 mo).ConclusionsTM patients on long term DFX without AA supplementation showed subnormal, AA levels. This was most pronounced in TM patients with higher liver and heart iron. The addition of AA to DFX normalized the AA levels but did not increase the e-LPI and LPI during 6 mo, indicating no apparent risk of iatrogenic toxicity by AA to DFX. Moreover, AA may enhance the efficacy of DFX in cardiac and hepatic iron. The small rise in SF versus fall in LIC in the DFX+AA arm might need further exploration. [Display omitted] [Display omitted] DisclosuresAydinok:Novartis Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Cerus: Research Funding; Shire: Research Funding. Cabantchik:Aferrix: Consultancy, Membership on an entity's Board of Directors or advisory committees; Hinoman: Consultancy; Novartis Pharmeceuticals: Honoraria, Speakers Bureau; Apopharma: Honoraria, Speakers Bureau.

Is Ferriscan - a Useful Tool for Diagnosing and Monitoring Tissue Iron Load after Acute Iron Intoxication?

▪Almost 16,000 iron exposures annually are reported in children less than six years of age in the United States. Deferoxamine is the iron-chelating agent of choice. Deferoxamine binds absorbed iron, and the iron-deferoxamine complex is excreted in the urine. Indications for treatment include shock, altered mental status, persistent GI symptoms, metabolic acidosis, pills visible on radiographs, serum iron level greater than 500 µg/dL, or estimated dose greater than 60 mg/kg of elemental iron. No clear end point of therapy is distinguished. Infusion of deferoxamine for 6-12 hours has been suggested for moderate toxicity. For severe toxicity, administer deferoxamine for 24 hours. Because these end points are arbitrary, observe the patient for the recurrence of toxicity 2-3 hours after the deferoxamine has been stopped. Complications of iron toxicity include the following: Infection with Yersinia enterocolitica, acute respiratory distress syndrome (ARDS) and fulminant hepatic failure, hepatic cirrhosis, pyloric or duodenal stenosis. Systemic toxicity is expected with an ingestion of 60 mg/kg. Ingestion of more than 250 mg/kg of elemental iron is potentially lethal.Although a low serum ferritin is an accurate measure of iron deficiency, there is no accurate serum or plasma marker for acute body-iron overload. Serum iron concentration and transferrin saturation do not quantitatively reflect body iron. Stores and should therefore not be used as surrogate markers of tissue iron overload. Liver iron concentration provides the best measure of total body iron stores and is a validated predictor of the risks a particular patient faces from the complications of iron toxicity. Several imaging noninvasive techniques are available for measuring liver iron concentration (LIC) . There are two validated MRI methods for quantitating the liver iron burden: the FerriScan and T2 methods. The noninvasive R2-MRI technique (FerriScan) is highly sensitive and specific for estimating LIC and is approved by the Food and Drug Administration for routine clinical use. However, it was not used to diagnose and monitor LIC in cases of acute iron intoxication.This 27 year old female nurse by profession self-referred to hematology clinic for evaluation of Iron overload after self injecting herself with 20 ampoules of IV iron Ferro sac (each ampoule containing 200 mg of iron, (4000 mg elemental iron, 60 mg/kg) . Her CBC on presentation showed Hb of 12.5 g/dl her baseline Hb 9 g/dl with serum iron of 28 (NR 9.0 - 30.4 umol/L) ,TIBC of 42 NR(45 - 80 umol/L ), ferritin 1001 (NR 24-336 mcg/l)Her clinical exam was unremarkable. Her MRI showed severe iron overload. 9 mg /g dray tissue (NR 0.17-1.8) Patient received chelation with deferasirox at dose of 30 mg /kg for 6 months when her ferriscan showed almost normal LIC of 2 mg /g dry tissue.This case report showed the value of ferriscan in diagnosing the degree of tissue iron overload and in monitoring chelation to a safe level of hepatic iron content. DisclosuresNo relevant conflicts of interest to declare.

Deferoxamine, Cerebrovascular Hemodynamics, and Vascular Aging: Potential Role for Hypoxia-Inducible Transcription Factor-1-Regulated Pathways.

Iron chelation therapy is emerging as a novel neuroprotective strategy. The mechanisms of neuroprotection are diverse and include both neuronal and vascular pathways. We sought to examine the effect of iron chelation on cerebrovascular function in healthy aging and to explore whether hypoxia-inducible transcription factor-1 activation may be temporally correlated with vascular changes. We assessed cerebrovascular function (autoregulation, vasoreactivity, and neurovascular coupling) and serum concentrations of vascular endothelial growth factor and erythropoietin, as representative measures of hypoxia-inducible transcription factor-1 activation, during 6 hours of deferoxamine infusion in 24 young and 24 older healthy volunteers in a randomized, blinded, placebo-controlled cross-over study design. Cerebrovascular function was assessed using the transcranial Doppler ultrasound. Vascular endothelial growth factor and erythropoietin serum protein assays were conducted using the Meso Scale Discovery platform. Deferoxamine elicited a strong age- and time-dependent increase in the plasma concentrations of erythropoietin and vascular endothelial growth factor, which persisted ≤3 hours post infusion (age effect P=0.04; treatment×time P<0.01). Deferoxamine infusion also resulted in a significant time- and age-dependent improvement in cerebral vasoreactivity (treatment×time P<0.01; age P<0.01) and cerebral autoregulation (gain: age×time×treatment P=0.04). Deferoxamine infusion improved cerebrovascular function, particularly in older individuals. The temporal association between improved cerebrovascular function and increased serum vascular endothelial growth factor and erythropoietin concentrations is supportive of shared hypoxia-inducible transcription factor-1-regulated pathways. Therefore, pharmacological activation of hypoxia-inducible transcription factor-1 to enhance cerebrovascular function may be a promising neuroprotective strategy in acute and chronic ischemic syndromes, especially in elderly patients. URL: http://www.clinicaltrials.gov. Unique identifier: NCT013655104.

The clinical effect of deferoxamine mesylate on edema after intracerebral hemorrhage.

Background and PurposeIt has been shown that 3 days of 62 mg/kg/day deferoxamine infusion (maximum dose not to exceed 6000 mg/day) is safe and tolerated by intracerebral hemorrhage (ICH) patients. The aim of this study was to investigate the efficacy of deferoxamine mesylate for edema resolution and hematoma absorption after ICH.MethodsFrom February 2013 to May 2014, spontaneous ICH patients diagnosed by computed tomography (CT) within 18 hours of onset were evaluated. Patients were randomly divided into two groups: an experimental group and a control group. The treatment of the two groups was similar except that the experimental group received deferoxamine mesylate. Patients were evaluated by CT and neurology scale at the time of admission, and on the fourth, eighth, and fifteenth day (or at discharge) after admission. Patients were followed up for the first 30 days and clinical data of the two groups were compared.ResultsForty-two patients completed 30 days of follow-up by May 2014; 21 cases in the experimental group and 21 cases in the control group. The control group’s relative edema volume on the fifteenth day (or discharge) was 10.26 ± 17.54, which was higher than the experimental group (1.91 ± 1.94; P < 0.05). The control group’s 1–8 day and 8–15 day relative hematoma absorption were greater than the experimental group (P < 0.05).The control group’s relative edema volume on the fourth, eighth, and fifteenth day (or discharge) was higher than the experimental group (P < 0.05). Neurological scores between the two groups were not statistically different on the fifteenth day (or discharge) or on the thirtieth day.ConclusionsDeferoxamine mesylate may slow hematoma absorption and inhibit edema after ICH, although further investigation is required to form definitive conclusions.Trial RegistrationChinese Clinical Trial Registry ChiCTR-TRC-14004979

Current possibilities of chelation therapy

Iron overload is one of the major problems in patients with hereditary and acquired anemias whose treatment uses regular packed red blood cell transfusions. The paper analyzes in detail all currently used iron store-estimating methods, such as a calculation method; determination of serum ferritin levels; measurement of liver iron concentration by both determining directly iron content in a biopsy specimen and indirectly by T2*-weighted magnetic resonance imaging (MRI (T2*)), estimation of myocardial iron by MRI (T2*). According to the current concept, the patients receiving regular packed red blood cell replacement transfusions need adequate chelation therapy, the goal of which is to reduce toxic iron in the cell and the extracellular space and total body iron stores, which can prevent irreversible organ and tissue damage, increase survival, and improve quality of life in patients. The paper gives an algorithm for chelation therapy (to choose a chelating agent for its primary use, to modify therapy in relation to a treatment goal, and to discontinue chelation therapy). Intensive chelation therapy as continuous intravenous deferoxamine infusion or combined therapy (simultaneous or successive use of 2 different iron chelating agents) is recommended in case of severe iron overload. This literature review analyzes in detail the dosing regimen and possible combinations of different iron chelating agents, as well as criteria for evaluating their efficiency and safety.

Intravenous Administration of Liposome Encapsulated DFO Efficiently Removes Iron from the Liver and Spleen of Iron Overloaded Mice

Introduction: Long-term red blood cell transfusions effectively sustains patients who have β-thalassemia, sickle cell anemia, and myelodysplastic syndromes but they also lead to excess iron accumulation in the body. Iron overload is a major cause of morbidity and mortality in transfusion dependent patients. Chelation therapy reverses iron accumulation but marketed chelators have drawbacks such as: long infusions of deferoxamine (DFO, Novartis), large oral tablets with adverse effects (Exjade, Novartis), or twice daily oral dosing (Ferriprox, ApoPharma). These attributes contribute to poor compliance and poor outcomes in iron overload patients. To overcome long infusions and high doses of current therapies we have devised a stable nanoliposome encapsulated DFO (LDFO) for the treatment of iron overload.Methods: LDFO composed of saturated soy phosphatidylcholine and cholesterol (3/2 molar ratio) is manufactured using a proprietary remote loading method that provides high encapsulation of DFO in 90 nm diameter liposomes. For pharmacokinetics and bioavailability studies, DFO and lipid concentrations in CF-1 mice plasma and tissues were analyzed by HPLC utilizing an in-house method. For iron removal efficacy studies, CF-1 mice were overloaded with iron dextran and after 10 days washout were treated with 100 mg/kg LDFO or unencapsulated DFO. Animals were sacrificed 5 days post treatment and tissue iron was measured by a ferrozine based spectroscopic assay.Results: The manufacturing method to prepare LDFO results in a 300 g DFO/mole lipid encapsulation ratio. The formulation has greater than 6 months stability at 4 ºC. LDFO is long circulating and the DFO is bioavailable. At 24 hr post I.V. injection, there is 30% ID DFO in plasma and 10% ID DFO/g in liver whereas unencapsulated DFO is not detectable. Preclinical single dose safety studies in CF-1 mice indicate that LDFO is well tolerated at 300 mg/kg I.V. and 1250 mg/kg I.P. In the iron dextran overload model, LDFO greatly reduces iron levels in the liver and spleen. The absolute efficiency of LDFO is greater than 50% on a mole LDFO injected /mole iron removed from the liver (P<0.0004, n=4) and spleen (P<0.01, n=4). This is corroborated by an elevated iron accumulation in urine and feces from LDFO.Conclusion: LDFO effectively removes iron from the liver and spleen with an overall molar efficiency > 50%. This high efficacy could lead to a dramatically improved treatment that increases compliance and provides substantially better management of iron overload than current treatments in patients suffering from iron overload conditions. DisclosuresTran:ZoneOne Pharma, Inc.: Employment. Noble:ZoneOne Pharma, Inc.: Employment, Equity Ownership. Hayes:ZoneOne Pharma, Inc.: Employment, Equity Ownership. Szoka:ZoneOne Pharma, Inc.: Consultancy, Equity Ownership.

간부전을 동반한 간세포암종 환자에서 경간동맥 Deferoxamine 투여 후 종양표지자 수치의 호전을 보인 1예

간부전을 동반한 간세포암종 환자에서 경간동맥 Deferoxamine 투여 후 종양표지자 수치의 호전을 보인 1예

Relationship among chelator adherence, change in chelators, and quality of life in thalassemia.

Thalassemia, a chronic blood disease, necessitates life-long adherence to blood transfusions and chelation therapy to reduce iron overload. We examine stability of health-related quality of life (HRQOL) in thalassemia and adherence to chelation therapy over time, especially after changes in chelator choice. Thalassemia Longitudinal Cohort participants in the USA, UK, and Canada completed the SF-36v2 (ages 14+) and the PF-28 CHQ (parents of children <14 years). Chelation adherence was defined as self-reported percent of doses administered in the last 4 weeks. Two hundred and fifty-eight adults/adolescents (mean 29.7 years) and 133 children (mean 8.5 years) completed a mean of 2.8-years follow-up. Children made few chelator changes, whereas a mean of 2.2 changes was observed among the 37% of adults/adolescents who made chelator changes, mainly due to patient preference or medical necessity. Physical HRQOL improved among those with lower iron burden (better health status) at baseline who made a single change in chelator, but declined among participants with multiple changes and/or high iron burden (worse health status). Mental health improved among participants with lower iron burden, but iron overload was negatively associated with social functioning. Adherence did not significantly change over follow-up except for an increase after a change from deferoxamine (DFO) infusion to oral deferasirox (p = 0.03). Predictors of lower adherence for adults/adolescents at follow-up included side effects, smoking, younger age, problems preparing DFO, increased number of days per week DFO prescribed, and lower physical quality of life . Strategies to balance medical needs with family, work, and personal life may assist in adherence.

Efficacy and safety of combined oral iron chelation therapy with deferasirox and deferiprone in a patient with beta-thalassemia major and persistent iron overload.

Efficacy and safety of combined oral iron chelation therapy with deferasirox and deferiprone in a patient with beta-thalassemia major and persistent iron overload.

Recurrent Nocardia Sepsis in a Patient With Sickle Cell Anemia Receiving Continuous Deferoxamine.

Nocardia species are ubiquitous soil-borne organisms that most commonly cause invasive disease in patients with defective cell-mediated immunity. We report a case of recurrent Nocardia sepsis in a patient with sickle cell disease and chronic iron overload, who was undergoing high-dose infusions of deferoxamine through a central venous catheter.