Heme Scavenging with Apohemoglobin-Haptoglobin Complex in Beta Thalassemia Intermedia Improves Anemia and Iron Indices: A Novel Therapeutic Approach

Abstract Beta-thalassemia intermediate (TI) is a genetic disorder of hemoglobin (Hb) synthesis characterized by anemia, ineffective erythropoiesis and iron overload. TI treatment is complex and regular transfusion therapy may be needed for growth failure, skeletal deformity, exercise intolerance, or when Hb levels decline because of progressive splenomegaly. Iron overload can be seen in TI, and serum ferritin measurement may often underestimate the extent of iron overload. There are limited therapeutic options for management of anemia and iron overload in TI. In this study, we look at the potential use of an engineered scavenger protein complex (apoHb-Hp) as a strategy to treat anemia in TI using a C57BL/6 mouse model. Sixteen beta-thalassemic mice (C57BL/6 heterozygous for the Hbb β-globin gene deletion (Hbb td3th/BrjK) (beta-thalassemia, Jackson Laboratory)) were treated with 50 µL of apoHb-Hp complex at a concentration of 27.95 mg/mL for six weeks to simultaneously scavenge cell-free Hb and free heme. Animal weight and RBC parameters (Hb, hematocrit (Hct), red blood cell (RBC) count, red cell distribution width) were measured at baseline and at 6 weeks post treatment. Total iron levels, transferrin concentration and transferrin saturation were measured at the third and sixth week of treatment. At the end of the experiment, the spleen and liver weights were measured and markers of liver function (Alanine transaminase (ALT), Aspartate transaminase (AST), Alkaline phosphatase (ALP)) were assessed. Further, total iron content of the liver and spleen was quantified using a using Perls' staining for non-heme ferric iron (Fe3+). The mean Hb at baseline for this cohort was 10.5 g/dL, Hct was 36% and RBC count was 7.6 10 6/ µL. After treatment with apoHb-Hp complex for 6 weeks, Hb levels improved to 11.3 g/dL and Hct to 38% vs. Hb of 10.1 g/dL and Hct of 35% for vehicle treated animals. The mean total RBC count at was 9.2 10 6/ µL following treatment with apoHb-Hp, and 7.7 10 6/ µL for vehicle treated animals at 6 weeks. Iron parameters were also improved, with lower mean serum iron levels in the apoHb-Hp treated group at 6 weeks when compared to vehicle control (90.5 µg/dL vs. 135.2 µg/dL, p < 0.05). Serum transferrin levels were 131.1 mg/dL vs. 90.3 mg/dL (p<0.05) for the apoHb-Hp and vehicle treated groups at 6 weeks respectively. Furthermore, when compared to control mice, apoHb-Hp mice had a significant reduction in both liver and spleen weights at 6 weeks- liver 5.7g vs. 5.2g (p<0.05) and spleen 3.8g vs. 3.4g (p<0.05) respectively. Finally, liver function tests also showed improvement following treatment with apoHb-Hp at 6 weeks, ALT 71.1 units/L vs. 85.5 units/L for the vehicle, AST levels 180.2 units/L vs. 217.6 for the vehicle (p <0.05) of, and ALP levels 247.3 units/L vs. 304.4 units/L (p <0.05). Our study demonstrates that apoHb-Hp can improve anemia and reduce iron toxicity in TI mice as well as improve liver and spleen parameters. Thus, apoHb-Hp may be a potential treatment strategy in this disease and merits further study. Figure 1 Figure 1. Disclosures Gopal: Alexion: Speakers Bureau; GBT: Consultancy; Pharming: Consultancy; Rigel Pharmaceuticals: Other: Clinical Trial, Research Funding.

Download Full-text

Growth Differentiation Factor 15 (GDF15) and Erythropoietin (EPO) Levels in Beta Talassemia Major Patients.

Blood ◽

10.1182/blood.v112.11.1881.1881 ◽

2008 ◽

Vol 112 (11) ◽

pp. 1881-1881

Author(s):

Ilaria Salussoglia ◽

Gisella Volpe ◽

Silvia Fracchia ◽

Simona Roggero ◽

Filomena Longo ◽

...

Keyword(s):

Iron Status ◽

Clinical Status ◽

Transferrin Saturation ◽

Iron Chelation ◽

Serum Levels ◽

Thalassemia Major ◽

Beta Thalassemia ◽

Transfusion Therapy ◽

Beta Thalassemia Major ◽

The Mean

Abstract Background: The serum level of GDF15 has been recently indicated as a possible marker of erythropoiesis (Tanno et al., Nature 2007) suggesting a role of its over-expression in contributing to iron overload in thalassemia syndromes by inhibiting hepcidin expression. The aim of present study has been to evaluate GDF15 serum levels in a homogeneous series of thalassemia patients and the relationship with transfusional parameters and iron status markers. Methods: A group of consecutive patients with beta thalassemia major followed at our institution were included in the study. All patients were on regular transfusion and iron chelation treatment. Quantification of GDF15 on serum samples was performed with DuoSet ELISA for human GDF15 (R&D Systems) following the manufacturer’s protocol (Tanno et al., Nature 2007). Each patient had also a blood test for haemoglobin (Hb), serum iron, ferritin, transferrin, transferrin saturation and EPO levels. Liver Iron Concentration by SQUID and cardiac iron by MRI T2* have been assessed. The mean hemoglobin levels of the previous year (pre-transfusional, post-transfusional and mean) have been calculated for each individual. The presence of mild thalassemic mutations was used to classify mild or severe genotype. Clinical status has been assessed on the presence/absence of main complications (heart disease, liver disease, diabetes, hypothyroidism). Statistical analysis was performed using the software Statistica (StatSoft). Results: One hundred-forty patients (73 male, 67 females) were studied. The mean age was 27.9 ± 9.0 years (range: 3.5–42). One hundred (71%) were splenectomised. Betathalassemia major patients had elevated GDF15 serum levels (mean 6892 ± 6894 pg/mL; range 720–52521) in comparison with healthy volunteers (273 ± 104 pg/mL; range 129–401). GDF 15 levels were strongly related to EPO levels (r=0,81; p<0,001). GDF15 levels were not related with age, gender, spleen, clinical status and iron markers. Patients with a severe genotype had higher GDF15 levels than mild genotype patients. GDF15 levels had a negative correlation with Hbs (p<0,05 for actual Hb and pre-transfusional Hb; p<0,001 for post-transfusional Hb and mean Hb). In thalassemia major patients with a severe genotype, GDF15 levels within thrice the normal range have been observed only in patients with pre-transfusional Hb above 9,6, post-transfusional Hb above 12,5 and a mean Hb above 11,3. Conclusions: In beta thalassemia major patients on regular transfusion and iron chelation, serum GDF15 levels are high, inversely related to the haemoglobin levels maintained. Further studies of this marker may lead to a rethinking of the optimal transfusion therapy in these conditions.

Download Full-text

Correlation between serum ferritin level, cardiac and hepatic T2-star MRI in patients with β-thalassemia major in Al-Diwaniya thalassemia center

International Journal of Research in Pharmaceutical Sciences ◽

10.26452/ijrps.v9ispl1.1392 ◽

2018 ◽

Vol 9 (SPL1) ◽

Author(s):

Alaa Mutter Jabur Al-Shibany ◽

AalanHadi AL-Zamili

Keyword(s):

Iron Overload ◽

Serum Ferritin ◽

Serum Ferritin Level ◽

Chelation Therapy ◽

Ferritin Level ◽

Thalassemia Major ◽

Beta Thalassemia ◽

Iron Level ◽

The Mean ◽

T2 Mri

Patients with transfusion dependent thalassemia major is often associated with iron overload. Proper use of iron chelators to treat iron overload requires an accurate measurement of iron levels. Magnetic resonance T2-star (T2* MRI) is the preferred method to measure iron level in the liver andthe heart. The goal of our study was to see if there is an association exists between serum ferritin level and T2* MRI results in patients with beta thalassemia major.This study was done in Al-Diwaniya Thalassemia center,Maternity and children teaching hospital,Iraq. During the period from 1st of January to 31st of October. Fifty eight patients with a diagnosis of beta thalassemia major were enrolled in the study. They were older than five years old,transfusion dependent and on chelation therapy. Hepatic and Myocardial T2*MRI and the mean serum ferritin levels were measured during the study period for all patients.There is a significant correlation was observed between serum ferritin level and cardiac T2*MRI (p=0.018 ). also a significant correlation was observed between serum ferritin and hepatic T2*MRI (p=0.02). Neither cardiac T2* MRI nor hepatic T2* MRI show any correlation with the mean age.our study also showa positive correlation between the patients withcardiac T2* MRI and the development of diabetes mellitus in contrast to hepatic T2* MRI in which there is no any correlation. Hypothyroidism was observedno correlation with either cardiac or hepatic T2* MRI.Our results showed a positiveassociation between hepatic, cardiac T2*MRI and serum ferritin levels.

Download Full-text

Effective and Safe Deferasirox Treatment of Patients with Various anemia's and Transfusional Iron-Overload in the Medical Practice: Results From Two German Observational Studies

Blood ◽

10.1182/blood.v118.21.5165.5165 ◽

2011 ◽

Vol 118 (21) ◽

pp. 5165-5165

Author(s):

Christian Junghanss ◽

Rudolf Schlag ◽

Bernd Gaede ◽

Matthias Moelle ◽

Steffen Doerfel ◽

...

Keyword(s):

Iron Overload ◽

Serum Ferritin ◽

Observational Studies ◽

Chelation Therapy ◽

Iron Chelation ◽

Iron Chelator ◽

Beta Thalassemia ◽

Final Visit ◽

Iron Chelation Therapy ◽

The Mean

Abstract Abstract 5165 Background: Progressive anaemia is highly prevalent amongst many malignant diseases leading to RBC transfusion-dependency. Therefore transfusion-related iron overload (IOL) is common in these patients (pts) and can result in multiple organ failure. Iron chelation therapy prevents organ failure, reduces the risk of infections and can improve hematopoesis in some diseases. The once-daily oral iron chelator deferasirox has been shown to reduce iron overload in pts with various transfusion-dependent anaemias assessed by serum ferritin (SF). Despite extensive knowledge of iron chelation in MDS or beta-thalassemia pts, data in pts with other anaemias is limited. Here, we present data from a subgroup of transfusion-related IOL pts that were included two non-interventional studies (EXTEND, EXJANGE) performed in Germany and who suffered from diseases other than MDS or beta thalassemia. Methods: 130 pts with various malignant diseases such as myeloproliferative disorders (43 pts, including 31 pts particular specified as myelofibrosis), acute myeloid leukaemia (14 pts), sickle cell anaemia (6 pts), aplastic anaemia (11), congenital aplastic anaemia (5) or Non-Hodgkin's lymphoma (6 pts) were treated with deferasirox in the daily-routine setting of office-based physicians and included in either the EXTEND or EXJANGE study. Patient with MDS or beta-thalassemia were also included in the studies, but are excluded from this analysis. Analysis is based on 1-year pooled data of these two, multicenter, non-interventional observational studies. Transfusion-dependent pts with IOL with or without prior chelation were enrolled and received the iron chelator deferasirox. Prescription of deferasirox, just as inclusion and exclusion criteria was in accordance with the terms of Exjade marketing authorization in the EU. Efficacy and safety parameters, including serum ferritin and adverse events (AEs), were collected in 2-monthly intervals. Results: 98 pts had no prior chelation therapy (51 M, 45 F, 2 missing; mean age 63.3, range 3.2–91.9 yrs) and a median baseline SF of 2,968 (range 561–11, 423) ng/mL. 32 pts had prior received prior chelation therapy (mainly with desferal; 17 M, 15 F; mean age 50.1, range 3.5–80.9 yrs) and a median baseline SF of 2,635 (range 539–19, 540) ng/mL. The mean number of prior red blood cell transfusions was 55. The mean prescribed daily dose of deferasirox at the first visit was 16.3 mg/kg/d rising up to 18.1 mg/kg/d after 12 months. During treatment, median SF levels clearly decreased from first to final visit [-806 ng/mL; p<0.0001 (explorative analysis)] in the chelation-naïve and also in the pre-chelated population [-300 ng/ml; p = 0.1705 (explorative analysis)]. The median observation period and days on therapy was 349 and 343 days, respectively. At final visit 74 pts (56.9%) were still on deferasirox therapy. Reasons for discontinuation by the final visit included 19 AEs (35.2%). 45 pts (34.6%) experienced an investigator assessed drug-related AE. The most common drug-related AEs were diarrhea (n=17; 37.8%), nausea (n=11; 24.4%) and blood creatinine increased (n=6; 13.3%). As in previous clinical trials, serum creatinine clearances showed a minor decrease over the study period (median decrease until final visit: 4 ml/min). Conclusion: Our analysis confirmed that deferasirox is effective and well tolerated in chelation-naïve as well as in previously chelated pts with transfusion-related IOL and diseases other than MDS or beta thalassemia. As baseline serum ferritin values were >2,500 ng/mL even in pts with prior chelation therapy, adequate chelation treatment should be considered earlier at a serum ferritin >1,000 ng/mL in pts with transfusion-dependent IOL for adequate iron chelation therapy. Disclosures: Junghanss: Novartis: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Haus:Novartis Pharma: Employment. Junkes:Novartis: Employment. Leismann:Novartis: Employment.

Download Full-text

PATTERN AND CLINICAL PROFILE OF PATIENTS WITH Β- THALASSEMIA IN REPEATED BLOOD TRANSFUSION

10.36106/ijar/7211096 ◽

2020 ◽

pp. 32-34

Author(s):

Ashok Badakali ◽

Deepti Shetty ◽

Manohar MR

Keyword(s):

Blood Transfusion ◽

Iron Overload ◽

Serum Calcium ◽

Chelation Therapy ◽

Iron Chelation ◽

Serum Phosphate ◽

Clinical Profile ◽

Beta Thalassemia ◽

Serum Phosphate Level ◽

The Mean

Chronic transfusions inevitably lead to iron overload as humans cannot actively remove excess iron. The cumulative effects of iron overload lead to significant morbidity and mortality, if untreated. The combination of transfusion and chelation therapy has dramatically extended the life expectancy of thalassemia patients, but with complications like hypocalcaemia. Hence, present study was undertaken to determine pattern and clinical profile of patients with β- thalassemia who are receiving repeated blood transfusion Methods: Hospital based study conducted at S. Nijalingappa Medical College and Hanagal Shri Kumareshwar hospital, Bagalkot. The study period was one and half year from 2015 to 2016. 53 beta thalassemia major cases fulfilling inclusion criteria were investigated after an informed consent, for serum calcium, serum phosphorous, serum ALP and paratharmone levels. Result: Among 53 transfusion dependent children studied, the mean age is 5.249 years. The study consisted of 32 (60.4%) males and 21 (39.6%) females. Maximum number of cases i.e. 29 (54.7%) were diagnosed at the age of 4-6 months. 50 (94.3%) were on iron chelation therapy. The mean serum calcium is 8.28 + 0.89 mg/dl. The mean serum phosphate is 6.40 + 0.80mg/dl, mean PTH is 14.96 + 15.49ng/L. The mean value of serum phosphate level is 14.96 + 15.49 ng/L. The mean ALP is 166.789 U/L. Conclusion: To get better results, regular testing is needed to detect the complications of the early stages with proper treatment of the factors and complications. Therefore, should be monitored to avoid complication related to hypocalcemia.

Download Full-text

Real-World Experience of Switching from Deferasirox Dispersible to Film-Coated Tablets: Impact on Adherence to Chelation Therapy, Iron Overload and Renal Function

Blood ◽

10.1182/blood-2018-99-119030 ◽

2018 ◽

Vol 132 (Supplement 1) ◽

pp. 1062-1062

Author(s):

Simon Cheesman ◽

Raakhee Shah ◽

Sara Trompeter ◽

Perla Eleftheriou ◽

Bernadette Hylton ◽

...

Keyword(s):

Renal Function ◽

Serum Creatinine ◽

Iron Overload ◽

Serum Ferritin ◽

Patient Adherence ◽

Beta Thalassemia ◽

Daily Dose ◽

Baseline Values ◽

The Mean ◽

The Impact

Abstract Background Chronic iron overload is an important complication of long-term blood transfusions for severe beta-thalassemias, sickle cell disease and other blood disorders. Iron chelation therapy (ICT) is required to bind and excrete excess iron, which would otherwise accumulate and lead to organ damage or failure. Deferasirox is a once-daily, orally administered ICT approved for the treatment of chronic iron overload due to frequent blood transfusions in patients with beta-thalassemia major and other anaemias. A film-coated tablet (FCT) formulation was launched in the UK in 2016 and replaced the dispersible tablet (DT) formulation. In the context of a randomised clinical trial, the FCT formulation showed greater adherence and patient satisfaction, better palatability and fewer tolerability concerns than the DT. Furthermore, treatment compliance by pill count was higher with FCT (92.9%) than with DT (85.3%) (Taher et al, 2017). Little information exists however about compliance, efficacy and tolerability outside of a clinical trial setting. Objectives We wished to assess in a 'real world' situation, the effects of switching the deferasirox formulation from DT to FCT on patient adherence to ICT, iron overload and renal function. Methods Patients receiving ICT with deferasirox who were switched from the DT to FCT formulations were followed over a 12-month period and results audited using hospital dispensing and biochemistry records. The date of the first FCT prescription was defined as baseline. The initial daily dose used for switching from DT to FCT was as per manufacturer's recommendations: 70% of the DT daily dose. The impact on iron overload was assessed by comparing serum ferritin levels at 3, 6, 9 and 12 months post-switch with baseline values. The impact on renal function was assessed by comparing serum creatinine levels at 3, 6, 9 and 12 months post-switch with baseline values as well as the number of serum creatinine increases of 30% or greater above baseline. The changes in serum ferritin and creatinine were subsequently analysed by paired t-test. The Proportion of Days Covered (PDC) was calculated as a measure of patient adherence to ICT in the 12 months before and after switching formulations. Results 74 patients switched from deferasirox DT to FCT with the following diagnoses: beta-thalassemia (n = 45), sickle-cell disease (9), thalassemia-intermedia (6), HbE-thalassemia (5), other transfusion-dependent disorders (9). The median age was 36 (range: 1-78yo), mean baseline serum ferritin was 2767µg/L (range: 412-8742), mean baseline creatinine was 64.5 umol/L (range: 17-140) and the median prescribed daily dose of DT was 1250mg (range: 62.5 - 3500). The mean PDC in the 12 months prior to switching formulations was 0.80 (range: 0.31-1.00). This increased to 0.91 (range: 0.21-1.00) in the 12 months following the switch to FCT. The median prescribed daily dose of FCT was 900mg (range: 90 - 2520) The mean changes in ferritin and creatinine at 3, 6, 9 and 12 months post-switch are shown in the table. 6 out of 74 patients (8%) had a creatinine increase of >30% from baseline whilst receiving the FCT, occurring after an average of 120 days (range: 30-260). All 6 patients were managed by dose adjustment of FCT and creatinine returned to the normal range in 5 out of 6 cases. Conclusions The switch from deferasirox DT to FCT resulted in improved patient adherence to chelation, a reduction in mean serum ferritin and a modest rise in mean serum creatinine. Some patients showed a reversible rise in creatinine from baseline. The median daily dose of FCT prescribed was 72% of the DT formulation, approximately equivalent according to the known bioavailability of the different preparations and suggesting that improvements in serum ferritin were due to the more consistent daily administration of the FCT rather than an increased daily deferasirox dose. We suggest that when the fall in ferritin is abrupt and/or to levels <1000µg/L, serum creatinine should be followed particularly carefully to avoid over-exposure to deferasirox from the FCT. We further speculate that patients who may have over-reported adherence to the DT prior to switching may be most susceptible to this effect. Reference Taher, A. T., et al. (2017). "New film-coated tablet formulation of deferasirox is well tolerated in patients with thalassemia or lower-risk MDS: Results of the randomized, phase II ECLIPSE study." American journal of hematology 92(5): 420-428. Table Table. Disclosures Garbowski: Vifor: Consultancy. Porter:Novartis: Consultancy; Cerus: Honoraria; Agios: Honoraria.

Download Full-text

Assessment of the Relationship Between Iron Overload Based on Cardiac T2* MRI and Fragmented QRS in Beta-Thalassemia Major Patients

Shiraz E-Medical Journal ◽

10.5812/semj.96612 ◽

2020 ◽

Vol 21 (8) ◽

Author(s):

Yazdan Ghandi ◽

Danial Habibi ◽

Aziz Eghbali

Keyword(s):

Iron Overload ◽

Chelation Therapy ◽

Thalassemia Major ◽

Beta Thalassemia ◽

Cardiac Iron ◽

Fragmented Qrs ◽

Beta Thalassemia Major ◽

Cardiac Iron Overload ◽

The Mean ◽

T2 Mri

Background: Cardiac involvement in beta-thalassemia major patients is an important cause of mortality. Therefore, in these patients, timely diagnosis of cardiac disorder is essential. Objectives: The present study aimed at determining the association between cardiac iron overload and fragmented QRS (fQRS). Methods: This cross-sectional study was conducted on 40 β-TM patients, aged 5 - 40 years. The presence of fQRS was evaluated in 12-lead surface electrocardiograms. Cardiac T2* MRI was performed to determine the iron overload. The patients were divided into four groups of chelation therapy. Results: The mean age of patients was reported to be 22.50 ± 6.75 years. The groups showed no significant difference regarding gender, age, or left ventricular ejection fraction. The presence of fQRS was detected in 10 patients (25%), while T2* value was lower than 20 ms in 10 patients (25%). The mean age of patients with and without fQRS was 26.23 ± 2.71 and 19.40 ± 2.61 years, respectively (P = 0.001). The univariate analysis indicated that fQRS had a significant relationship with cardiac iron overload (OR = 5; 95% CI: 1.04 - 23.99; P < 0.044). The multiple logistic regression analysis represented a significant association between iron overload and fQRS (OR = 5.556; 95% CI: 1.027 - 30.049). The sensitivity and specificity of the fQRS against MRI were equal to 50% and 83.3% respectively. Conclusions: The absence of fQRS on ECGs could be a good predictor of the lack of cardiac iron overload in β-TM patients. The results showed that fQRS might indicate the no need for close monitoring for cardiac overload with cardiac MRI and aggressive chelation therapy.

Download Full-text

Latin American Registry of Patients (Pts) with Transfusional Hemosiderosis (Th): The RELATH Study.

Blood ◽

10.1182/blood.v110.11.4013.4013 ◽

2007 ◽

Vol 110 (11) ◽

pp. 4013-4013 ◽

Cited By ~ 1

Author(s):

Rodolfo Cancado ◽

Ivan Angulo ◽

Zaida Plumacher ◽

Mariela Moreno ◽

Adriana Linares ◽

...

Keyword(s):

Iron Overload ◽

Latin American ◽

African Ancestry ◽

Tertiary Care ◽

Iron Chelation ◽

Refractory Anemia ◽

Beta Thalassemia ◽

Liver Iron ◽

The Mean ◽

Rbc Transfusion

Abstract In Latin America (LA), miscegenation of populations of Mediterranean and African ancestry has occurred for several centuries, thus facilitating the spread of hemoglobin variants. The prevalence of thalassemias, sickle-cell disease (SCD) and other hemoglobinopathies, as well as of myelodysplastic syndromes (MDS) and other diseases associated with TH is largely unknown in LA. As a retrospective registry of pts with TH in LA, the RELATH Study provides a unique opportunity to gain insight about the prevalence of TH and the patterns of care for these pts in LA. Participating countries include Brazil, Colombia, Mexico, Peru, and Venezuela. Target accrual is approximately 1,000 patients. Cases are accrued by large-volume, tertiary-care hematology centers located in large cities through a CRF designed for the study. Treatment and pt evaluation are not influenced by the study. Eligible pts have age >2 yr, consultation in the participating institutions at least once since 01/04, any disorder requiring chronic red-blood-cell (RBC) transfusion, receipt of >9 RBC units, at least one value of serum ferritin >1000 mcg/L, and/or a liver iron content (LIC) >2 mg/g dry weight (pts. with leukemia are excluded). Between Jan/06 and May/07, 239 pts have been accrued, 236 of which are evaluable. The mean age was 29.2 +/− 20.4 (range, 2 to 92), and 53.8% of pts were female. Ethnic distribution was Hispanic (41.0%), African (34.6%), and Caucasian ancestry (24.4%). The most frequent diagnoses were SCD (43.6%), beta-thalassemia major (17.4%), aplastic anemia (13.6%), and MDS (7.2%, 53.3% of which had refractory anemia). RBC transfusion was > 9 in 100% and >19 in 89.8% of pts, and mean ferritin was 2564 +/− 1834 mcg/L. LIC determination was not available or not done in 90.6% of cases. The level of hemoglobin at which transfusion was indicated was 7 to 10 g/dL in 60.7%, and 6 g/dL or less in 38.1% (N/A in 1.3%). The mean number of transfusions received was 12.2 +/− 8.8/yr (range, 1 to 80). Iron overload was assessed using ferritin (93.2%), and TH related complications were evaluated with echocardiogram (42.8%), and liver US (27.5%). TH-related complications were reported in 82.2% of cases (66.5% of pts had hepatic complications, 32.6% endocrine, 16.1% cardiac). Iron-chelation therapy was given to 39.8% of pts, more frequently on the basis of ferritin (27.5%), number of transfusions (18.2%), and complication from iron overload (5.5%). Deferoxamine (93.6%) and deferasirox (6.4%) were the most frequent chelators. In most cases, treatment was still ongoing, but reasons for discontinuation were pt refusal (4.7%), drug no longer available (4.2%), and poor compliance (3.8%). In conclusion, this preliminary report from the ongoing RELATH study shows that a registry is feasible and may provide valuable information regarding TH in various countries of LA. In addition, the study suggests so far that most LA patients undergoing chronic transfusion develop TH, whose complications could be prevented by more effective use of iron chelation, which was relatively low in this sample.

Download Full-text

Pulmonary dysfunction in children with beta thalassemia major in relation with iron overload - a cross sectional hospital based study

Asian Journal of Medical Sciences ◽

10.3126/ajms.v6i5.11782 ◽

2015 ◽

Vol 6 (5) ◽

pp. 47-50 ◽

Cited By ~ 3

Author(s):

A Boddu ◽

A Kumble ◽

S Mahalingam ◽

BS Baliga ◽

B Achappa

Keyword(s):

Iron Overload ◽

Serum Ferritin ◽

Thalassemia Major ◽

Beta Thalassemia ◽

P Value ◽

Pulmonary Dysfunction ◽

Cross Sectional ◽

Transfusion Therapy ◽

Respiratory Dysfunction ◽

Respiratory Impairment

Background: Previously many patients with thalassemia major died from severe anemia during first decade, but with modern transfusion therapy many now survive beyond childhood. Because of such therapy, however excessive iron deposition occurs in lungs and causing respiratory dysfunction. Respiratory impairment occurs because of defective chelation and repeated transfusions. Objectives: To a) study pattern of respiratory impairment using spirometry, b) estimate iron overload by measuring serum ferritin levels, c) correlate a&b. Methodology:Thalassemia children >7year, on regular blood transfusion were included in the study after getting institutional ethical clearance .Standardised pulmonary function test was done using spirometry. Iron overload was assessed using serum ferritin levels. Severity of pulmonary dysfunction was correlated with serum ferritin levels. Results:Total of 42 children were included 62% were males and 38% were females (with median age 12yrs). By spirometry 95% had restrictive pattern of respiratory dysfunction. Mean ferritin value was 4152. Out of them10 (23.8%) mild, 25(59%) moderate and 5(12%) severe dysfunction based on FEV1 and FVC. The mean ferritin values in severe respiratory dysfunction is 6275 which is significantly higher when compared to moderate (4249) and mild (3066) pattern of respiratory dysfunction. None of the children had evidence of CCF. Significant correlation (p value=0.003) was found between severity of pulmonary dysfunction with ferritin values and also with weight of the child (p value=0.007). No other significant correlation found between severity pattern and transfusion index, age or height. Conclusion:Restrictive pattern is most common pulmonary dysfunction seen in chronic iron overloaded thalassemia major children. Regular blood transfusions with adequate chelation decrease incidence of pulmonary dysfunction. Screening of all thalassemia children using spirometry is need of the hour. DOI: http://dx.doi.org/10.3126/ajms.v6i5.11782Asian Journal of Medical Sciences Vol.6(5) 2015 47-50

Download Full-text

Iron Overload Status in Patients with Non-Transfusion-Dependent Thalassemia in China

Blood ◽

10.1182/blood.v128.22.1287.1287 ◽

2016 ◽

Vol 128 (22) ◽

pp. 1287-1287

Author(s):

Rong rong Liu ◽

Yu mei Huang ◽

Peng Peng ◽

Xiao yun Wei ◽

Yu Lei ◽

...

Keyword(s):

Iron Overload ◽

Serum Ferritin ◽

Genetic Disorder ◽

Chinese Patients ◽

Beta Thalassemia ◽

Iron Level ◽

Liver Iron ◽

Liver Iron Overload ◽

Medical University ◽

Hbh Disease

Abstract Background: Non-transfusion-dependent thalassemia (NTDT) is a genetic disorder most commonly including beta-thalassemia intermedia (Beta-TI), HbE/Beta thalassemia (HbE/Beta thalassemia), and hemoglobin H disease (HbH disease). NTDT patients can be at risk of iron overload due to increased intestinal iron absorption triggered by chronic anemia, ineffective erythropoiesis and, possibly, decreased serum hepcidin. Despite NTDT is popular in southern China, there is little data evaluating iron overload in Chinese patients. This study aimed at investigating the occurrence, prevalence and severity of iron overload in Chinese population with NTDT. Methods: We evaluated the serum ferritin (SF), liver iron concentration (LIC) and cardiac T2* in 158 NTDT patients (83 with HbH disease, 45 with Beta-TI and 30 with HbE/Beta thalassemia) in China. The median age was 22 years old. The main characteristics of these patients along with the main results of the study were summarized in Table 1. Blood samples were obtained for the assessment of hemoglobin (Hb) and serum ferritin (SF) levels. LIC was assessed by using validated R2 magnetic resonance imaging [MRI] (FerriScan®). Cardiac iron level was measured by MRI T2*. Patients were scanned with MRI 1.5 T (Siemens Avanto, Germany). The study was performed at the First Affiliated Hospital of Guangxi Medical University. LIC < 3mg Fe/g dw and cardiac T2* > 20ms was considered normal. Abnormal LIC can be divided into mild: 3-7mg Fe/g dw, moderate: 7-15mg Fe/g dw, severe: >15mg Fe/g dw. All patients or parents/guardians provided their written informed consent to participate in this study. The study was approved by the Medical Ethics Committee of the First Affiliated Hospital of Guangxi Medical University. Results: The median SF level of 158 NTDT patients was 1,037(27.0-19,704) ng/ ml. LIC was detected in 155 patients (98.1%) and the median LIC value was 8.9(0.6-43) mg Fe/g dw. There were 15 patients (60%) (8 with HbH disease, 5 with Beta-TI and 2 with HbE/Beta thalassemia)<10 years old found liver iron overload. The youngest patient with liver iron overload was 5 years old with 5.6mg Fe/g dw in LIC. Cardiac T2*was assessed in 111 patients (70.2%) and the median cardiac T2* was 32.8(7.5-75.1)ms. The 7 patients (4.4%) (4 with HbH disease and 3 with Beta-TI) had cardiac T2*=<20ms. There was a significant correlation between LIC and SF (r=0.809, p<0.001). No correlation between LIC and Hb, cardiac T2* values can be verified. There was a significant correlation between LIC and age (r=0.497, p<0.001)(Fig 1). The levels of LIC in patients > 30-year old group are significantly higher than those in other groups (Fig 2).The patients with Beta-TI and HbE/Beta thalassemia showed a statistically significant lower Hb and higher values of SF and LIC than those of HbH disease patients. Conclusions: Chinese NTDT patients have a high prevalence of iron overload. The iron overload in patients with Beta-TI and HbE/Beta thalassemia are more serious than those in HbH disease patients. The age of patient is a risk factor of iron overload in NTDT patient. Patients > 30 years old have a high burden of iron overload. Our data shows that the first assessment of MRI LIC should be performed as early as 5 years old. Disclosures No relevant conflicts of interest to declare.

Download Full-text

Iron Overload Occurs Very Early In Newly-Diagnosed Patients With Congenital, Transfusion-Dependent Anemias

Blood ◽

10.1182/blood.v122.21.4704.4704 ◽

2013 ◽

Vol 122 (21) ◽

pp. 4704-4704

Author(s):

Antonios Kattamis ◽

Polyxeni Delaporta ◽

Ioannis Papassotiriou ◽

Dimitra Kyriakopoulou ◽

Natalia Tourkantoni ◽

...

Keyword(s):

Iron Overload ◽

Chelation Therapy ◽

Conflicts Of Interest ◽

Initial Period ◽

Transferrin Saturation ◽

Young Patients ◽

Beta Thalassemia ◽

Newly Diagnosed ◽

Transfusion Therapy ◽

Transfusion History

Systematic transfusions are lifesaving for patients with severe congenital anemias, but they eventually lead to iron overload and the indispensable necessity of iron chelation therapy. Current official guidelines for the starting time of chelation therapy derives from data obtained with the use of desferrioxamine, which has been shown to have significant toxicity in very young patients, especially when used in low iron burden. No data exist on the use of the oral iron chelators in this setting. The purpose of this study was to evaluate the changes of iron parameters at the initial period of transfusion therapy in newly diagnosed patients with congenital anemias Methods Nine patients participated in this study. One patient was diagnosed with Diamond-Blackfan anemia, one patient with severe alpha-thalassemia, while 7 had beta-thalassemia. Three of the beta-thalassemia started transfusions at 1.5, 2 and 5 years, respectively. All others started transfusions between 2-4 months of age. Iron, transferrin saturation, ferritin levels. serum transferrin receptors (sTfR), were estimated by standard methods, while labile plasma iron (LPI) by the FeROS LPI kit (Aferrix, Ltd, Israel). The main results of the study show that: 1) transferrin saturation increases rapidly with transfusions (mean levels after 4 transfusions 49.2% (range: 23.8-90.5%), mean after 6 transfusions 69.1% (range: 39.5-112%)), though it has significant diversity in between patients, as indicated also by one patient that continued to have transferrin saturation at 65% even after 12 sessions. Transferrin saturation significantly correlates with ferritin levels (r=0.763, p<0.0001), with the number of previous transfusions (r=0.486, p=0.002) and with the levels of sTfR, which is also an index of the degree of erythropoiesis (r=0.550, p<0.001). The increase of ferritin correlates also with the sTfR levels (r=0.697, p<0.0001), while the rate of increasing transferrin saturation per transfusion correlates to sTfR levels (r=0.486, p=0.002). LPI levels appears early in the transfusion history and correlates with transfusion saturation. Discussion The results of the study indicate that iron overload starts early in the transfusion history of young patients with transfusion-dependent anemias. These findings dispute current guidelines suggesting starting chelation therapy, when the patients have already received 10 transfusions or when ferritin levels reach more than 1000ug/dl. Disclosures: No relevant conflicts of interest to declare.

Download Full-text