No abstract available.
beta-Thalassemia* ; Chelation Therapy* ; Humans ; Iron Overload* ; Iron*

An increase in biochemical concentrations of non-transferrin bound iron (NTBI) within the patients with an increase in serum iron concentration was evaluated with the following objectives: (a) Iron overloading diseases/conditions with free radicle form of ‘iron containing’ reactive oxygen species (ROS) and its imbalance mediated mortality, and (b) Intervention with iron containing drugs in context to increased redox iron concentration and treatment induced mortality. Literature search was done within Pubmed and cochrane review articles. The Redox iron levels are increased during dys-erythropoiesis and among transfusion recipient population and are responsive to iron-chelation therapy. Near expiry ‘stored blood units’ show a significant rise in the ROS level. Iron mediated ROS damage may be estimated by the serum antioxidant level, and show reduction in toxicity with high antioxidant, low pro-oxidant levels. Iron drug therapy causes a significant increase in NTBI and labile iron levels. Hospitalized patients on iron therapy however show a lower mortality rate. Serum ferritin is a mortality indicator among the high-dose iron therapy and transfusion dependent population. The cumulative difference of pre-chelation to post chelation ROS iron level was 0.97 (0.62; 1.32; N=261) among the transfusion dependent subjects and 2.89 (1.81–3.98; N=130) in the post iron therapy ‘iron ROS’ group. In conclusion, iron mediated mortality may not be mediated by redox iron among multi-transfused and iron overloaded patients.
Drug Therapy ; Ferritins ; Hepcidins ; Humans ; Iron Overload ; Iron ; Mortality ; Oxidation-Reduction ; Reactive Oxygen Species

Objective: To analyze the influencing factors of iron metabolism assessment in patients with myelodysplastic syndrome. Methods: MRI and/or DECT were used to detect liver and cardiac iron content in 181 patients with MDS, among whom, 41 received regular iron chelation therapy during two examinations. The adjusted ferritin (ASF) , erythropoietin (EPO) , cardiac function, liver transaminase, hepatitis antibody, and peripheral blood T cell polarization were detected and the results of myelofibrosis, splenomegaly, and cyclosporine were collected and comparative analyzed in patients. Results: We observed a positive correlation between liver iron concentration and ASF both in the MRI group and DECT groups (r=0.512 and 0.606, respectively, P<0.001) , only a weak correlation between the heart iron concentration and ASF in the MRI group (r=0.303, P<0.001) , and no significant correlation between cardiac iron concentration and ASF in the DECT group (r=0.231, P=0.053) . Moreover, transfusion dependence in liver and cardiac [MRI group was significantly associated with the concentration of iron in: LIC: (28.370±10.706) mg/g vs (7.593±3.508) mg/g, t=24.30, P<0.001; MIC: 1.81 vs 0.95, z=2.625, P<0.05; DECT group: liver VIC: (4.269±1.258) g/L vs (1.078±0.383) g/L, t=23.14, P<0.001: cardiac VIC: 1.69 vs 0.68, z=3.142, P<0.05]. The concentration of EPO in the severe iron overload group was significantly higher than that in the mild to moderate iron overload group and normal group (P<0.001) . Compared to the low-risk MDS group, the liver iron concentration in patients with MDS with cyclic sideroblasts (MDS-RS) was significantly elevated [DECT group: 3.80 (1.97, 5.51) g/L vs 1.66 (0.67, 2.94) g/L, P=0.004; MRI group: 13.7 (8.1,29.1) mg/g vs 11.6 (7.1,21.1) mg/g, P=0.032]. Factors including age, bone marrow fibrosis, splenomegaly, T cell polarization, use of cyclosporine A, liver aminotransferase, and hepatitis antibody positive had no obvious effect on iron metabolism. Conclusion: There was a positive correlation between liver iron concentration and ASF in patients with MDS, whereas there was no significant correlation between cardiac iron concentration and ASF. Iron metabolism was affected by transfusion dependence, EPO concentration, and RS.
Ferritins ; Humans ; Iron ; Iron Overload ; Liver/metabolism* ; Myelodysplastic Syndromes/therapy* ; Primary Myelofibrosis ; Retrospective Studies ; Splenomegaly

Humans ; Iron Overload ; diagnosis ; etiology ; therapy ; Myelodysplastic Syndromes ; diagnosis ; metabolism ; therapy

OBJECTIVETo explore the application value of detection of Hepcidin together with indicator of iron overload on clinical diagnosis and treatment of MDS with iron overload by measuring Hepcidin and iron load indices of transfusion dependent myelodysplastic syndrome (MDS) patients.

METHODSEnzyme-linked immunosorbent assay (ELISA), radioimmunoassay and colorimetry were used to determine the Hepcidin, serum ferritin (SF) and serum iron (SI) levels of 106 serum samples from 68 cases of transfusion dependent MDS patients, 30 serum samples of MDS patients without transfusion and 60 serum samples of controls.

RESULTSFor MDS group, Hepcidin level in blood transfusion < 9 U subgroup was significantly higher than that in control group \[(583 ± 50) µg/L vs (175 ± 35) µg/L\] and there was a strong positive correlation between Hepcidin levels and SF (r = 0.976), but no correlation between Hepcidin and SI (r = 0.284); Both Hepcidin and SF level in transfusion 9 ∼ 24 U subgroup was significantly higher than those in control group \[(665 ± 80) µg/L vs (175 ± 35) µg/L; (1445 ± 275) µg/L vs (112 ± 26)µg/L\]; whereas for SI level, there was no difference between transfusion 9 ∼ 24 U subgroup and the control group. Hepcidin did not correlate with SF or SI; For blood transfusion > 24 U group, all of Hepcidin, SF and SI levels were higher than those in control groups \[(703 ± 64) µg/L vs (175 ± 35) µg/L; (2587 ± 352) µg/L vs (112 ± 26)µg/L; (20 ± 4) µg/L vs (14 ± 4) µmol/L\], Hepcidin negatively correlated with SF and SI (r = -0.536; r = -0.456). Hepcidin levels of RARS patients were significantly lower than RAEB patients \[(260 ± 40) µg/L vs (442 ± 51) µg/L\], and there was no significant difference between RARS group and control group regardless of the number of blood transfusion.

CONCLUSIONBoth Hepcidin and SF levels in MDS patients regardless of transfusion dependent or not, or the number of blood transfused were higher than those of normal controls, the increase of Hepcidin can not synchronize with the increase of SF level due to the increased blood transfusion, when blood transfusion > 24 U, Hepcidin level showed a negative relationship with SF and SI, reflecting the decreased ability of Hepcidin to inhibit body iron absorption during the increase of blood transfusion, which finally would lead to iron overload. We can predict the occurrence of iron overload in transfusion dependent MDS patients by dynamic monitoring concentration of Hepcidin.

Adult ; Aged ; Aged, 80 and over ; Antimicrobial Cationic Peptides ; blood ; Blood Transfusion ; Female ; Ferritins ; blood ; Hepcidins ; Humans ; Iron ; blood ; Iron Overload ; Male ; Middle Aged ; Myelodysplastic Syndromes ; blood ; therapy

BACKGROUND: Iron overload is a risk factor affecting all patients with thalassemia intermedia (TI). We aimed to determine whether there is a relationship of serum ferritin (SF) and alanine aminotransferase (ALT) with liver iron concentration (LIC) determined by R2 magnetic resonance imaging (R2-MRI), to estimate the most relevant degree of iron overload and best time to chelate in patients with TI. METHODS: In this cross-sectional study, 119 patients with TI (mean age years) were randomly selected and compared with 120 patients who had a diagnosis of thalassemia major (TM). Correlations of LIC, as determined by R2-MRI, with SF and ALT levels, were assessed in all participants. A P-value < 0.05 was considered statistically significant. RESULTS: SF and LIC levels were lower in patients with TI than in those with TM; only ferritin values were significant. We found a statistically significant relationship between SF and LIC, with cut-off estimates of SF in patients with TI who had splenectomy and those who entered puberty spontaneously (916 and 940 ng/mL, respectively) with LIC >5 mg Fe/g dry weight (P < 0.0001). A significant relationship was also found for patients with TI who had elevated ALT level (63.5 U/L), of 3.15 times the upper normal laboratory limit, using a cut-off for LIC ≥5 mg Fe/g dry weight. CONCLUSION: We determined the cut-off values for ALT and SF indicating the best time to start iron chelation therapy in patients with TI, and found significant correlations among iron overload, SF, and ALT.
Adolescent ; Alanine Transaminase ; beta-Thalassemia* ; Chelation Therapy ; Cross-Sectional Studies ; Diagnosis ; Ferritins* ; Humans ; Iron Overload ; Iron* ; Liver* ; Magnetic Resonance Imaging ; Puberty ; Risk Factors ; Splenectomy ; Thalassemia*

Haemochromatosis is characterised by elevated transferrin saturation (TSAT) and progressive iron loading that mainly affects the liver. Early diagnosis and treatment by phlebotomy can prevent cirrhosis, hepatocellular carcinoma, diabetes, arthropathy and other complications. In patients homozygous for p.Cys282Tyr in HFE, provisional iron overload based on serum iron parameters (TSAT >45% and ferritin >200 μg/L in females and TSAT >50% and ferritin >300 μg/L in males and postmenopausal women) is sufficient to diagnose haemochromatosis. In patients with high TSAT and elevated ferritin but other HFE genotypes, diagnosis requires the presence of hepatic iron overload on MRI or liver biopsy. The stage of liver fibrosis and other end-organ damage should be carefully assessed at diagnosis because they determine disease management. Patients with advanced fibrosis should be included in a screening programme for hepatocellular carcinoma. Treatment targets for phlebotomy are ferritin <50 μg/L during the induction phase and <100 μg/L during the maintenance phase.
Male ; Humans ; Female ; Hemochromatosis/therapy* ; Hemochromatosis Protein/genetics* ; Carcinoma, Hepatocellular/complications* ; Iron Overload/genetics* ; Ferritins ; Liver Cirrhosis/complications* ; Iron ; Fibrosis ; Liver Neoplasms/complications* ; Transferrins

BACKGROUND/AIMS: The financial burden of caring for iron-related complications (IRCs) is an emerging medical problem in Korea, as in Western countries. We produced a preliminary estimate of the costs of treating patients for IRCs. METHODS: The medical records of patients who had received multiple transfusions were reviewed. Newly developed cardiomyopathy, heart failure, diabetes mellitus, liver cirrhosis, and liver cancer were defined as IRCs. The costs of laboratory studies, medication, oxygenation, intervention, and education were calculated using working criteria we defined. Costs that had a definite causal relationship with IRCs were included to produce as accurate an estimate as possible. RESULTS: Between 2002 and 2006, 650 patients with hematologic diseases, including 358 with acute leukemia, 102 with lymphoma, 58 with myelodysplastic syndrome or myeloproliferative disease, 46 with multiple myeloma, and 31 with chronic leukemia, received more than 10 units of red blood cells. Nine patients developed IRCs. The primary diagnoses of eight patients were aplastic anemia and that of one patient was chronic lymphocytic leukemia. Two patients who had diabetes were excluded because one was treated at another hospital and the other was diagnosed as oxymetholone-induced diabetes. Of the seven patients included, liver cirrhosis developed in two, heart failure in four, and diabetes mellitus in three. Some of them had two diagnoses. The total cost attributed to IRCs for the seven patients was 47,388,241 KRW (approximately 50,000 USD). CONCLUSIONS: The medical costs of IRCs are considerable, and more effective iron-chelating therapy is necessary to save medical resources and improve patient care. More in the way of comprehensive health and economic studies of IRCs are needed to allow both clinicians and health-policy makers to make better decisions.
Adult ; Costs and Cost Analysis/methods ; Erythrocyte Transfusion/adverse effects ; Female ; Health Care Costs/*statistics & numerical data ; Hematologic Diseases/therapy ; Humans ; Iron/blood ; Iron Chelating Agents/*economics/therapeutic use ; Iron Overload/*economics/etiology/*therapy ; Korea ; Male ; Middle Aged ; Retrospective Studies

OBJECTIVETo explore the efficacy and safety of deferasirox in aplastic anemia (AA)patients with iron overload.

METHODSA single arm, multi- center, prospective, open- label study was conducted to evaluate absolute change in serum ferritin (SF)from baseline to 12 months of deferasirox administration, initially at a dose of 20 mg·kg(-1)·d(-1), and the safety in 64 AA patients with iron overload.

RESULTSAll patients started their deferasirox treatment with a daily dose of 20 mg · kg(-1) ·d(-1). The mean actual dose was (18.6±3.60) mg · kg(-1)·d(-1). The median SF decreased from 4 924 (2 718- 6 765)μg/L at baseline (n=64) to 3 036 (1 474- 5 551)μg/L at 12 months (n=23) with the percentage change from baseline as 38%. A median SF decrease of 651 (126-2 125)μg/L was observed at the end of study in 23 patients who completed 12 months' treatment, the median SF level decreased by 1 167(580-4 806)μg/L [5 271(3 420-8 278)μg/L at baseline; 3 036(1 474-5 551)μg/L after 12 months' treatment; the percentage change from baseline as 42% ] after 12 months of deferasirox treatment. The most common adverse events (AEs) were increased serum creatinine levels (40.98%), gastrointestinal discomfort (40.98%), elevated liver transaminase (ALT: 21.31%; AST: 13.11%)and proteinuria (24.59%). The increased serum creatinine levels were reversible and non-progressive. Of 38 patients with concomitant cyclosporine use, 12(31.8%)patients had two consecutive values >ULN, 10(26.3%)patients had two consecutive values >1.33 baseline values, but only 1(2.6%)patient's serum creatinine increased more than 1.33 baseline values and exceeded ULN. For both AST and ALT, no patients experienced two post- baseline values >5 ×ULN or >10 × ULN during the whole study. In AA patients with low baseline PLT count (less than 50 × 10(9)/L), there was no decrease for median PLT level during 12 months' treatment period.

CONCLUSIONSAA patients with iron overload could achieve satisfactory efficacy of iron chelation by deferasirox treatment. The drug was well tolerated with a clinically manageable safety profile and no major adverse events.

Anemia, Aplastic ; drug therapy ; Benzoates ; therapeutic use ; Blood Transfusion ; China ; Ferritins ; blood ; Humans ; Iron ; blood ; Iron Chelating Agents ; therapeutic use ; Iron Overload ; drug therapy ; Liver ; Prospective Studies ; Triazoles ; therapeutic use

OBJECTIVETo observe the status of iron deposition in patient with β thalassemia major, and to formulate appropriate treatment strategies.

METHODThe data of status of transfusion and chelation in 135 patients aged from 6 years and 4 months to 17 years and 11 months with β thalassemia major were collected and analyzed. Serum ferritin levels were determined and cardiac and hepatic iron deposition was determined using MRI T2(*) technology.

RESULTOf the 135 cases studied, 66 were male, and 69 were female, their average age was 12.1 years. Serum ferritin (SF) was determined for 111 cases, it varied from 1 086.8 µg/L to 15 011.5 µg/L. Among them, 16 cases had SF level <2 000 µg/L (14.5%) , in 41 cases SF were between 2 000 and 4 000 µg/L (36.0%) ;in 54 cases SF >4 000 µg/L (48.7%) . Liver MRI T2(*) results showed that in only 8 cases (5.9%) iron content in the liver was in normal range, 19 cases (14.9%) showed mild liver iron deposition;34 (25.2%) moderate and 74 (54.8%, the youngest one was only 6 years and 4 months of age) had severe iron deposition respectively. Cardiac MRI T2(*) showed that in 89 cases (65.9%) iron content in the heart was in normal range;19 cases (14.1%) had mild cardiac iron deposition and 27 (20.0%) presented severe iron deposition (the youngest one was only 9 years and 3 months of age) . SF level was obviously related to liver and cardiac iron deposition (MRI T2(*)) r and P value were -0.284, 0.003 and -0.374, 0.000 respectively. In 108 cases regular transfusion and chelation were delayed due to financial problem. The late and insufficient dosage administered and irregular chelation caused the higher SF level and the severe iron deposition.

CONCLUSIONThe survival status of β thalassemia major in China is worrisome. Majority of them had not received regular transfusion and chelation. Liver and cardiac iron deposition occur early and had a high incidence.

Adolescent ; Child ; Female ; Ferritins ; blood ; Humans ; Iron ; metabolism ; Iron Chelating Agents ; adverse effects ; therapeutic use ; Iron Overload ; epidemiology ; etiology ; Liver ; metabolism ; Magnetic Resonance Imaging ; Male ; Myocardium ; metabolism ; Radiography ; Retrospective Studies ; Transfusion Reaction ; beta-Thalassemia ; diagnostic imaging ; metabolism ; therapy