scholarly journals THERAPEUTIC VALUE OF COMBINED THERAPY WITH DEFERASIROX AND SILYMARIN ON IRON OVERLOAD IN CHILDREN WITH BETA THALASSEMIA

2013 ◽  
Vol 5 (1) ◽  
pp. e2013065 ◽  
Author(s):  
Adel Abd elhaleim Hagag
Keyword(s):  
Iron Overload ◽  
Serum Ferritin ◽  
Iron Status ◽  
Iron Chelator ◽  
University Hospital ◽  
Beta Thalassemia ◽  
Control Group ◽  
Healthy Children ◽  
Number Of Patients

abstractBackground: Beta thalassemia is an inherited hemoglobin disorder resulting in chronic hemolytic anemia requiring life-long blood transfusion that cause iron overload. Silymarin plays a role as oral iron chelator and hepatoprotective agents in thalassemic patients.The aim of this work was to determine silymarin value as an iron chelator in thalassemic patients with iron overload.Patients and Methods: This study was conducted on 40 children with beta thalassemia major under follow-up at Hematology Unit, Pediatric Department, Tanta University Hospital having serum ferritin level more than 1000 ng/ml and was divided in two groups. Group IA: Received oral Deferasirox (Exjade) and silymarin for 6 months. Group IB: Received oral Deferasirox (Exjade) and placebo for 6 months and 20 healthy children serving as a control group in the period between April 2011 and August 2012 and was performed after approval from research ethical committee center in Tanta University Hospital and obtaining an informed written parental consent from all participants in this research. Results: Serum ferritin levels were markedly decreased in group IA cases compared with group IB (P= 0.001). Conclusion: From this study we concluded that, silymarin in combination with Exjade can be safely used in treatment of iron-loaded thalassemic patients as it showed good iron chelation with no sign of toxicity. Recommendations: Extensive multicenter studies in large number of patients with longer duration of follow up and more advanced methods of assessment of iron status is recommended to clarify the exact role of silymarin in reduction of iron over load in children with beta thalassemia.  

Evaluation of Iron Status by Serum Ferritin Level in Iranian Carriers of Beta Thalassemia Minor

2008 ◽  
Vol 78 (45) ◽  
pp. 204-207 ◽  
Author(s):  
Hamid Hoorfar ◽  
Shohreh Sadrarhami ◽  
Ammar Hassanzadeh Keshteli ◽  
Samaneh Khanpour Ardestani ◽  
Manijeh Ataei ◽  
...  
Keyword(s):  
Iron Overload ◽  
Serum Ferritin ◽  
Iron Status ◽  
Ferritin Level ◽  
Beta Thalassemia ◽  
Control Group ◽  
Similar Data ◽  
Thalassemia Minor ◽  
The Mean ◽  
Harmful Effects

Background: Conflicting data exists on iron metabolism in adults with beta thalassemia minor (BTM). The purpose of this study was to evaluate the serum ferritin (SF) levels in Iranian adults with BTM in order to determine the iron status in these subjects. Methods: Eighty four (41 males, 43 females) Iranian adults with BTM and 102 (55 males, 47 females) healthy subjects as a control group were enrolled in the study. SF level was measured by immunoradiometric assay (IRMA). Results: The mean SF concentration in the BTM group was 101.84 ± 8.5 μg/L, which was higher than the mean SF in non-BTM subjects (67.98 ± 5.4 μg/L, p = 0.001). Comparing SF concentrations between BTM males and males in the control group showed that the SF level was significantly higher in BTM males (150.57 ± 75.13 μg/L vs. 96.66 ± 56.79 μg/L, p < 0.001). Similar data was found for females (55.38 ± 47.94 μg/L in the BTM group vs. 34.42 ± 25.72 μg/L in the non-BTM group, p = 0.01). Conclusion: This study showed that BTM may play a role in improving iron status in females with BTM. However in males, BTM can lead to iron overload. Therefore, we suggest determining the levels of SF in subjects with BTM, especially in males, to avoid harmful effects of iron overload in early stages of the disorder.

Clinical-Reported Outcomes Of Deferoxamine Versus Deferasirox In The Treatment Of Homozygous BetaThalassemia

2018 ◽  
Vol 9 (SPL1) ◽  
Author(s):  
Zeina A Munim Al-Thanoon ◽  
Zeina A Munim Al-Thanoon ◽  
Mustafa Basil ◽  
Nasih A Al-Kazzaz
Keyword(s):  
Serum Ferritin ◽  
Iron Chelation ◽  
Iron Chelator ◽  
Beta Thalassemia ◽  
Control Group ◽  
Current Standard ◽  
Cross Sectional ◽  
Significant Difference ◽  
Multiple Blood ◽  
Group 2

Iron chelation therapy with deferoxamine (DFO),the current standard for the treatment of iron overload in patients with betathalassemia,requires regular subcutaneous or intravenous infusions. This can lead to reduced quality of life and poor adherence,resulting in increased morbidity and mortality in iron-overloaded patients with beta-thalassemia. Deferasirox (DFX) is an orally administered iron chelator that has been approved for use in many countries. The requirement of an effective,well tolerated iron chelator with a less demanding mode of administration has led to the development of deferasirox. The present study was aimed to compare the satisfaction and compliance with deferoxamine versus deferasirox (Exjade®),a novel oral iron chelator in patients with transfusion - dependent beta- thalassemia. A cross-sectional,single-center investigation study was carried out in the Thalassemia Center of Ibn-Atheer Teaching Hospital in Nineveh province,Iraq. One hundred and eight thalassemic patients aged between 2- 20 years old having received multiple blood transfusions and a serum ferritin greater than 1500 ng/ml. Patients were randomised into two groups. Group 1 received deferoxamine at a dose of 20-50mg/kg/day and group 2 received deferasirox at the dose of 10-30 mg/kg/day. Another 56 apparently healthy volunteers were used as a control group. The assessment of chelation was done during the period between November 2013 and February 2014 by measurement of serum ferritin. Satisfaction and compliance was assessed by using a special questionnaire prepared by the researcher. Out of the 108 thalassemic patients enrolled there was no discontinuation in treatment with the two drugs under study. The serum ferritin did not change significantly in any of the chelation groups. In comparison with the patients who were treated with DFO,those receiving DFX reported a significantly higher rate of compliance and satisfaction (P < 0.05). However,no significant difference was observed between the two groups regarding their satisfaction (P > 0.05).Compliance with deferasirox (50 %) was more than that with deferoxamine (20 %). Satisfaction with deferoxamine was significantly lower than deferasirox (p= 0.00).

scholarly journals Zinc Status in Beta-Thalassemia Major

2021 ◽  
Vol 9 (B) ◽  
pp. 149-153
Author(s):  
Khalaf Hussein Hasan ◽  
Hasan Abdulla Aswad ◽  
Aspazija Sofijanova
Keyword(s):  
Serum Ferritin ◽  
Ferritin Level ◽  
Disease Onset ◽  
Serum Zinc ◽  
Thalassemia Major ◽  
Adverse Outcomes ◽  
Beta Thalassemia ◽  
Control Group ◽  
Healthy Children ◽  
Zinc Status

BACKGROUND: Zinc is one of the most important minerals incorporated in the enzymes of the human body. Zinc may be deficient in patients with the β-thalassemia major with possible adverse outcomes. AIM: The purpose of this study was to assess the serum zinc status in β-thalassemia major patients in Duhok city. PATIENTS, MATERIAL, AND METHODS: In this case–control study, 70 children with β-thalassemia major (2–12 years) of both genders were enrolled and were matched with 70 apparently healthy children for age and sex. A venous blood sample was obtained from each child for the measurement of serum zinc and serum ferritin levels at Jin Center in Duhok City between January 1 and June 30, 2017. RESULTS: The mean serum zinc in the thalassemia patients (74.79 [±25.14] μg/dl) was significantly lower compared to the control group (93.61 [±15.12] μg/dl), (p = 0.0001). The serum zinc was not significantly different in thalassemia patients in terms of age, disease onset, gender, height, weight, body mass index, amount of blood transfusion, and type of chelation. There was a statistically significant correlation between serum zinc levels with a serum ferritin level of patients. CONCLUSION: The study showed that thalassemia patients have significantly lower serum levels of zinc with no relation to medical factors.

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 ◽  
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.

scholarly journals The Pros and Cons of Splenectomy in Transfusion Dependent Thalassemia Patient

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 4901-4901 ◽  
Author(s):  
Adisak Tantiworawit ◽  
Somying Dumnil ◽  
Nichanan Osataphan ◽  
Thanawat Rattanathammethee ◽  
Sasinee Hantrakool ◽  
...  
Keyword(s):  
Iron Overload ◽  
Data Base ◽  
Serum Ferritin ◽  
Iron Concentration ◽  
Older Age ◽  
Lower Percentage ◽  
Categorical Variables ◽  
Beta Thalassemia ◽  
Control Group ◽  
Fisher Exact Test

Abstract Introduction One of the treatment modalities in transfusion dependent thalassemia (TDT) patient is splenectomy which aims to ameliorate red cell transfusion. However, not all thalassemia patients respond to splenectomy. Moreover, splenectomy may increase many unfavorable consequences. The study about the efficacy and complications after splenectomy is limited and the effect of splenectomy on iron overload is still unclear. This study aims to investigate the long-term efficacy of splenectomy, factor predicting a response to splenectomy, the consequences of splenectomy complications, CBC parameter changes and the effect on iron overload parameters after splenectomy. Methods All TDT patients (PRC transfusion ≥3 units/year), aged >15 years who had splenectomy were recruited from our hematology division data base. Clinical characteristics including age, sex, age at splenectomy, operation date, hemoglobin (Hb) typing were collected. PRC transfusion requirement (unit/year) and CBC were collected 1 year before splenectomy, 1 year and 5 year post splenectomy. In the complication cohort, TDT patients with intact spleen were recruited into control group. The sample size was calculated that at least 33 patients (66.6% from splenectomy group and 33.3% from non-splenectomy group) needed to be recruited to have 80% power to detect a difference in complication at an alpha level of 0.05. The diagnosis of pulmonary hypertension (PHT) was based on the echocardiogram performed by the cardiologist and using definition from the 2015 ESC guideline. The thrombosis events were collected from medical record. The iron overload was compared by serum ferritin, liver iron concentration (LIC) and cardiac iron concentration were assessed by MRI of liver and cardiac T2*. The associated factors of efficacy and complication for splenectomy were compared using Chi-squared test or Fisher exact test for categorical variables and T-test or Mann-Whitney test and repeated measure mixed model for continuous variables. Multivariate regression analysis was used to identify relationships between variables with the level of significance was defined as P value <0.05. Results Fifty TDT patients were included from the data base. In term of splenectomy efficacy, 21 patients (42%) has been changed from TDT to non-transfusion dependent thalassemia (NTDT) patients after splenectomy and 25 patients (50%) had 50% reduction in PRC transfusion. The significant factors associated with changing from TDT to NTDT were genotype of thalassemia (P=0.001). HbH disease and beta thalassemia/HbE (β/E) patients were the group who had higher response (28.57% and 52.38%, respectively) compared to HbH with CS (9.52%) and homozygous beta-thalassemia (9.51%). Lower percentage of neutrophils (<50%) was associated with lower response (P=0.02). Older age at the time of splenectomy (>10 year old) was associated with higher response after splenectomy (P = 0.005). CBC before splenectomy, 1 and 5 years after splenectomy were compared. Mean Hb level was increased from 6.0 to 8.2 and 7.7 g/dL (P<0.001) and platelet was increased from 234,866 to 714,473 and 675,579 cells/cu.mm. (P<0.001). Sixty-four patients were included in the complication cohort, (44 patients in splenectomy group and 20 patients in non-splenectomy group). The baseline characteristics including age, sex, Hb, ferritin were similar between 2 groups. The splenectomy group had significant higher tricuspid valve regurgitation velocity (TRV) compared to non-splenectomy group (2.54 m/s vs. 2.31 m/s, P=0.029). The prevalence of PHT and thrombosis were higher in splenectomy group (27.3% vs. 15% and 9.1% vs. 0%, respectively). Serum ferritin, LIC and cardiac T2* were not different between the 2 groups. From multivariable analysis, the only significant factor for predicting PHT was the longer duration after splenectomy (p=0.045). Conclusion Splenectomy had benefit in some TDT patients. Factors that predict a higher response to splenectomy were thalassemia type (HbH and β/E), higher neutrophil percentage and older age at the time at splenectomy. Hb and platelet was significantly increased after splenectomy. In term of complication, splenectomy group had significant higher TRV and tended to have more prevalence of PHT and thrombosis. The longer time post splenectomy was the only significant factor for developing PHT. Disclosures No relevant conflicts of interest to declare.

scholarly journals Transient Elastography of Liver in Hb E Beta Thalassemia: A Novel Tool to Determine Hepatic Iron Overload?

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 3368-3368
Author(s):  
Debmalya Bhattacharyya ◽  
Maitreyee Bhattacharyya ◽  
Saswata Chatterjee ◽  
Abhijit Chowdhury ◽  
Pramit Ghosh
Keyword(s):  
Iron Overload ◽  
Serum Ferritin ◽  
Serum Ferritin Level ◽  
Ferritin Level ◽  
Liver Stiffness ◽  
Beta Thalassemia ◽  
Hepatic Iron ◽  
Hepatic Iron Overload ◽  
Number Of Patients ◽  
T2 Mri

Abstract Introduction: Transient Elastography (TE) of liver is a well established tool to measure liver stiffness, mainly used for assessment of hepatic fibrosis due to chronic hepatitis. Liver biopsy is the gold standard test for measurement of liver iron concentration (LIC) whereas T2* MRI is the best available non-invasive method for the same in thalassemia. We intended to use hepatic TE as an alternative cheaper tool to assess hepatic iron overload so that it can be applied to larger number of patients. Objective: To assess degree of liver stiffness by TE in patients with HbE beta thalassemia and correlate the findings with LIC calculation by T2* MRI of liver. Materials and Method: 53 patients with HbE beta thalassemia from the thalassemia clinic of Institute of Haematology and Transfusion Medicine, Medical College, Kolkata were enrolled for the study. Patients with known liver disease were excluded. Baseline data like HbE%, mutations, transfusion requirement, growth status, serum ferritin level etc were collected. All of them underwent TE of liver in the School of Digestive and Liver Diseases, IPGMER using the FibroScan Touch 502 machine (Di Marco et al, British Journal of Haematology, Volume 148,3, 476-479, February 2010). 20 randomly selected patients were also assessed by T2*MRI of liver for hepatic iron assessment at the same time. LIC calculation was done from T2* value (J S Hankins et al, Blood, 14 May 2009, Volume 113:20). Data were analyzed by SPSS software-19, IBM. Results: The patients with HbE beta thalassemia had a mean HbE level of 53.66 (±18.45) %. Common beta mutations [mostly IVS-1-5(G-C)] usually found in this part of India, were detected. Mean and median age of the study population was 24.11±13.11 years and 20 years, respectively. Median age of 1st transfusion was 11 years. 35.84% patients were non-transfusion dependent. 39/53 patients had facial deformity and growth retardation. Mean baseline hemoglobin was 7.10±0.76 gm/ dl. Mean serum ferritin level was 3183.66±338.45 ng/ml. TE showed 30.18 % patients had severe liver stiffness (Liver stiffness measurement, LSM >15 kPa) whereas 43.34% had minimum stiffness (LSM≤7 kPa). No significant statistical correlation was found between serum ferritin and LSM. 12/20 patients showed very high calculated LIC (>15 mg/g) and lower T2* value (<1.8 ms) whereas only 10% of them showed mildly elevated calculated LIC. Rest had intermediate LIC. Discussion: There is lack of data regarding hepatic iron overload in HbE beta thalassemia and so also from this part of India. There was a trend that higher the age, higher was the LSM irrespective of the serum ferritin level though not found statistically significant (Figure 1). Serum ferritin level was also not significantly correlated with the calculated LIC in those 20 patients assessed with T2* MRI. 2 patients with mildly elevated LIC had a high ferritin level. Preliminary report indicates that with increase in LSM there was increase in calculated LIC also. Statistical analysis revealed patients with LSM≥7.2 kPa had moderate or severe hepatic iron overload and thus undermine the need for routine T2*MRI. The cut off value signifies that patients with LSM<7.2 kPa might or might not have significantly high liver iron overload, so obviously to be assessed by T2*MRI (Table 1). Therefore use of TE may be an alternative preliminary diagnostic method to gauge hepatic iron overload in HbE beta thalassemia patients. It would be of more value in countries like India where T2* MRI facility is not yet feasible in many centers catering to huge number of HbE-beta thalassemia patients. However, further exploration with larger number of patients is necessary to establish association of LIC and LSM in a more robust way. Conclusion: In resource-poor countries like India, TE may be a relatively cheap tool to be used as a marker of hepatic iron overload in future. Table 1. Finding Cut off: ROC (TE-value and LIC categories), n=20 Positive if Greater Than or Equal Toa Sensitivity 1 - Specificity 2.3 1.00 1.00 3.4 1.00 .50 4.4 .94 .50 5.7 .88 .50 6.2 .83 .50 6.5 .77 .50 7.2 .77 .00 8.2 .72 .00 8.85 .66 .00 9.45 .61 .00 10.2 .55 .00 11.85 .50 .00 13.85 .44 .00 15.75 .38 .00 18.3 .33 .00 22.9 .27 .00 27.9 .22 .00 35.9 .16 .00 44.7 .11 .00 48.0 .05 .00 49.8 .00 .00 Table 2. The smallest cutoff value is the minimum observed test value minus 1, and the largest cutoff value is the maximum observed test value plus 1. LSM more than 7.2 had a sensitivity of 77.2 % and specificity of 100%. Figure 2. Figure 2. Disclosures No relevant conflicts of interest to declare.

scholarly journals Evaluation of Erythroferrone, Hepcidin, and Iron Overload Status in Iraqi Transfusion-dependent β-Thalassemia Major Patients

2019 ◽  
Author(s):  
Hasan Smesam ◽  
Hasan Qazmooz ◽  
Sareh Arjmand ◽  
Hussein Kadhem Al-Hakeim ◽  
Seyed Omid Ranaei‐Siadat,
Keyword(s):  
Iron Overload ◽  
Iron Status ◽  
Iron Chelation ◽  
Fold Increase ◽  
Thalassemia Major ◽  
Beta Thalassemia ◽  
Control Group ◽  
Beta Globin ◽  
Beta Thalassemia Major ◽  
Globin Chains

Beta thalassemia major (&beta;-TM) disorder characterized by the lack, or severe reduction in the production of hemoglobin &beta;-globin chains. The standard protocol for the management of &beta;-TM is blood transfusion and iron chelation therapy to reduce the iron overload state. The present study aimed to investigate the relationships between two iron regulatory hormones, hepcidin (HEPC) and erythroferrone (ERFE) levels and iron status parameters (ISPs) in Iraqi patients with &beta;-TM. ISPs and hormones were measured in sixty patients and compared with thirty healthy controls. The results indicated significant changes in different iron status parameters, while ferritin (FRT) with the ~11 fold increase showed the most change. Significant reduction in HEPC and increase in ERFE levels were detected in patients as compared to the control group, while no direct correlation was identified with the other measured ISPs. Receiver operating characteristic (ROC) analysis showed that the z-score of the composite of ERFE+FRT has a full diagnostic ability for &beta;-TM. In conclusion, our finding indicated the correlation between different ISPs, FRT as the leading predictor of iron overload and tow main iron regulatory hormones.

scholarly journals Major Depression in Children with β-Thalassemia Major is Strongly Associated with the Number of Blood Transfusions, Iron Overload and Increased Levels of Interleukin-1β

2019 ◽  
Author(s):  
Hussein Kadhem Al-Hakeim ◽  
Asawer Hassan Najm ◽  
Arafat Hussein Al-Aldujaili ◽  
Michael Maes
Keyword(s):  
Iron Overload ◽  
Inflammatory Responses ◽  
Iron Status ◽  
Thalassemia Major ◽  
Treatment Modalities ◽  
Beta Thalassemia ◽  
Blood Transfusions ◽  
Healthy Children ◽  
Beta Thalassemia Major ◽  
Increased Risk

Beta-thalassemia major (&beta;-TM) patients are treated with repeated blood transfusions, which may cause iron overload (IO), which in turn may induce immune aberrations. Patients with &beta;-TM have an increased risk of major depressive disorder (MDD). The aims of the present study are to examine whether repeated blood transfusions, IO and immune-inflammatory responses are associated with MDD in children (6-12 years) with &beta;-TM. The Children&rsquo;s Depression Inventory (CDI), iron status (serum iron, ferritin, transferrin, TS%) and serum levels of CCL11, IL-1&beta;, IL-10, and TNF-&alpha; were measured in &beta;-TM with (n=54) and without (n=57) MDD and in healthy children (n=55). The results show that MDD in &beta;-TM is associated with a greater number of blood transfusions, increased IO and IL-1&beta; levels. Partial Least Squares path analysis shows that 68.8% of the variance in the CDI score is explained by the number of blood transfusions, IO, and increased levels of IL-1&beta; and TNF-&alpha;. The latter two cytokines partly mediate the effects of IO on the CDI score, while the effects of blood transfusions on the CDI score are partly mediated by IO and the path from IO to immune activation. IO is also associated with increased IL-10 and lower CCL11 levels but these alterations are not significantly associated with MDD. In conclusion, blood transfusions may be causally related to MDD in &beta;-TM children and their effects are in part mediated by increased IO and the consequent immune-inflammatory response. The results suggest that not only IO and its consequences including inflammation and ferroptosis, but also other factors related to the number of transfusions may cause MDD including psychosocial stressors. Current treatment modalities with folic acid and vitamin C are insufficient to attenuate IO and immune-inflammatory responses and to prevent MDD is children with &beta;-TM undergoing blood transfusions.

P754Iron status indices (transferrin saturation, serum ferritin) in the course of acute myocarditis: relations with neurohormonal activation, cardiac dysfunction and clinical recovery

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
P Franczuk ◽  
A Kosiorek ◽  
M Tkaczyszyn ◽  
M Drozd ◽  
A Zapolska ◽  
...  
Keyword(s):  
Acute Phase ◽  
Serum Ferritin ◽  
Cardiac Dysfunction ◽  
Troponin I ◽  
Iron Status ◽  
Acute Myocarditis ◽  
Transferrin Saturation ◽  
Control Group ◽  
Neurohormonal Activation

Abstract Introduction Acute myocarditis (MCD) can progress to post-myocarditis cardiomyopathy. Immune response is the major pathophysiological trigger leading to MCD. Optimal iron status is essential for the functioning of immune cells, cardiomyocytes and cardiofibroblasts. Therefore, there are premises to consider iron metabolism as a significant modulator of complex pathophysiology of MCD. Purpose We aimed to assess iron status in the course of MCD and relate it with clinical and laboratory measures. Methods We prospectively enrolled consecutive patients hospitalized for acute MCD in 2 tertiary referral cardiology centers during 2015–2018 and followed them up for 30 weeks. MCD was diagnosed based on the following criteria: 1) new onset symptoms suggestive of myocarditis (effort intolerance, dyspnea, palpitations or chest pain), 2) elevated high sensitivity cardiac troponin I (hs-cTnI), 3) exclusion of obstructive coronary artery disease. Results Study group comprised 41 patients with confirmed MCD [age: 31 (26–34) years, men: 95%] and 15 healthy age- and gender-matched subjects [age: 30 (28–33) years, men: 87%]. All patients survived hospitalization and follow-up, no subject needed ventricular assist device. Patients with MCD had lower LVEF (56±10% vs. 69±14%) and higher CRP [32 (14–8754) vs. 3 (3–3) mg/l], NT-proBNP [452 (240–877) vs. 33 (18–46) pg/ml], hs-cTnI [7.3 (3.3–12.8) vs. 0,01 (0.01–0.01) μg/l] than the control group (all p<0.001). Regarding iron status, MCD group presented higher serum ferritin [213 (121–386) vs. 135 (84–210) μg/l] and lower transferrin saturation (TSAT) [21±10 vs. 28±15%] (all p<0.05). In patients with MCD ferritin correlated with CRP (r=0.46, p<0.01), TSAT correlated neither with CRP nor with ferritin (all p>0.02). Patients with MCD and NT-proBNP >1000 pg/ml had lower TSAT (16±8 vs. 23±9%; p<0.05) and LVEF (47±13 vs. 59±7%; p<0.001) than the remaining subjects. No difference in ferritin was observed (p>0.2). 46% of patients during acute phase of MCD had LVEF≤55% – these patients presented lower TSAT (17±8% vs. 24±10%) and higher NT-proBNP – [577 (436–1657) vs. 358 (167–499) pg/ml] (all p<0.05). After 30 weeks only in 13% patients LVEF≤55% persisted and related to lower baseline TSAT (9±1% vs. 21±9%) and higher CRP (147±113 vs. 52±40 mg/l) (all p<0.05). LVEF≤55% was not related to ferritin (both p>0.2). After 6 weeks of follow-up patients with MCD already presented higher LVEF (61±8%; p<0.05) and haemoglobin [14.7 (14.0–15.7) g/dl], lower CRP [3 (3–3) mg/l], NT-proBNP [34 (25–67) pg/ml], hs-cTnI [0.01 (0.01–0.01)], ferritin [124 (78–168) μg/l] and higher TSAT (26±7%) (all p<0.01). There was no further change in these parameters within the next 24 weeks (all p>0.2). Conclusions Iron status is deranged in acute MCD. Serum ferritin is an indicator of inflammatory response, whereas TSAT relates to neurohormonal activation and cardiac dysfunction. Iron status normalizes within 6 weeks after acute phase of MCD. Acknowledgement/Funding This research was financially supported by the National Science Centre (Poland) grant number 2014/13/B/NZ5/03146.

scholarly journals ACQUIRED HYPOGONADOTROPIC HYPOGONADISM (AHH) IN THALASSAEMIA MAJOR PATIENTS: AN UNDERDIAGNOSED CONDITION?

2016 ◽  
Vol 8 ◽  
pp. 2016001 ◽  
Author(s):  
Vincenzo De Sanctis
Keyword(s):  
Liver Disease ◽  
Iron Overload ◽  
Serum Ferritin ◽  
Iron Status ◽  
Pubertal Development ◽  
Hypogonadotropic Hypogonadism ◽  
Well Being ◽  
Control Group ◽  
Mineral Density ◽  
Iron Concentrations

IntroductionIn males, acquired hypogonadotropic hypogonadism (AHH) includes all disorders that damage or alter the function of gonadotropin-releasing hormone (GnRH) neurons and/or pituitary gonadotroph cells. The clinical characteristics of AHH are androgen deficiency and a lack, delay or halt of pubertal sexual maturation. AHH lead to decreased libido, impaired erectile function and strength, a worsened sense of well being and degraded quality of life (QOL).Patients and methodsWe studied 11 adult men with thalassemia major (TM) aged between 26 to 54 years (mean ± SD: 34.3 ± 8.8 years) with AHH. Twelve age- and sex-matched TM patients with normal pubertal development were used as a control group. All patients were on regular transfusions and iron chelation therapy.Fasting venous blood samples were collected two weeks after  transfusion to measure serum concentrations of IGF-1, free thyroxine (FT4), thyrotropin (TSH), cortisol,  luteinizing hormone (LH), follicle stimulating hormone (FSH), total testosterone (TT), prolactin and estradiol (E2), glucose, urea, creatinine and electrolytes (including calcium and phosphate). Liver functions and screening for hepatitis C virus seropositivity (HCVab and HCV-RNA) were performed. Iron status was assessed by measuring serum ferritin levels, and evaluation of iron concentrations in the liver (LIC) and heart using MRI- T2*.   Bone mineral density was measured at the lumbar spine (L1-L4) for all patients with AHH by dual energy X-ray absorptiometry (DXA) using Hologic QDR 4000 machine.ResultsThe mean basal serum LH and FSH concentrations in AHH patients were 2.4 ± 2.2 IU/L  and 1.2 ± 0.9 IU/L respectively; these, values were significantly lower compared to the control group. Semen analysis in 5 patients with AHH proved azoospermia in 3 and  oligoasthenozoospermia in 2. The percentage of patients with serum ferritin level >2000 ng/ml was significantly higher in AHH patients compared to controls (45.4 % versus 8.3%, p: 0.043). Heart iron concentrations (T2* values) were significantly lower inAHH patients compared to controls (p: 0.004). Magnetic resonance imaging in the 3 azoospermic patients revealed volume loss and reduction of pituitary signal intensity.  Using DXA, 63.6 % (7/11) of patients with AHH were osteoporotic and 36.3 % (4/11) were osteopenic.  ConclusionsIn our thalassemic patients iron overload and chronic liver disease appear to play a role in the development of AHH.  Treatment of AHH in TM patients is an important and vibrant field for improving their health and QOL. Early identification and management of AHH is very crucial to avoid long-term morbidity, including sexual dysfunction and infertility. Therapy aims to restore serum testosterone to the mid–normal range. Many exciting opportunities remain for further research and therapeutic development.Key words:Acquired hypogonadotropic hypogonadism, thalassemia, iron overload, liver disease.IntroductionIn males, acquired hypogonadotropic hypogonadism (AHH) includes all disorders that damage or alter the function of gonadotropin-releasing hormone (GnRH) neurons and/or pituitary gonadotroph cells. The clinical characteristics of AHH are androgen deficiency and a lack, delay or halt of pubertal sexual maturation. AHH lead to decreased libido, impaired erectile function and strength, a worsened sense of well being and degraded quality of life (QOL).Patients and methodsWe studied 11 adult men with thalassemia major (TM) aged between 26 to 54 years (mean ± SD: 34.3 ± 8.8 years) with AHH. Twelve age- and sex-matched TM patients with normal pubertal development were used as a control group. All patients were on regular transfusions and iron chelation therapy.Fasting venous blood samples were collected two weeks after  transfusion to measure serum concentrations of IGF-1, free thyroxine (FT4), thyrotropin (TSH), cortisol,  luteinizing hormone (LH), follicle stimulating hormone (FSH), total testosterone (TT), prolactin and estradiol (E2), glucose, urea, creatinine and electrolytes (including calcium and phosphate). Liver functions and screening for hepatitis C virus seropositivity (HCVab and HCV-RNA) were performed. Iron status was assessed by measuring serum ferritin levels, and evaluation of iron concentrations in the liver (LIC) and heart using MRI- T2*.   Bone mineral density was measured at the lumbar spine (L1-L4) for all patients with AHH by dual energy X-ray absorptiometry (DXA) using Hologic QDR 4000 machine.ResultsThe mean basal serum LH and FSH concentrations in AHH patients were 2.4 ± 2.2 IU/L  and 1.2 ± 0.9 IU/L respectively; these, values were significantly lower compared to the control group. Semen analysis in 5 patients with AHH proved azoospermia in 3 and  oligoasthenozoospermia in 2. The percentage of patients with serum ferritin level >2000 ng/ml was significantly higher in AHH patients compared to controls (45.4 % versus 8.3%, p: 0.043). Heart iron concentrations (T2* values) were significantly lower inAHH patients compared to controls (p: 0.004). Magnetic resonance imaging in the 3 azoospermic patients revealed volume loss and reduction of pituitary signal intensity.  Using DXA, 63.6 % (7/11) of patients with AHH were osteoporotic and 36.3 % (4/11) were osteopenic.  ConclusionsIn our thalassemic patients iron overload and chronic liver disease appear to play a role in the development of AHH.  Treatment of AHH in TM patients is an important and vibrant field for improving their health and QOL. Early identification and management of AHH is very crucial to avoid long-term morbidity, including sexual dysfunction and infertility. Therapy aims to restore serum testosterone to the mid–normal range. Many exciting opportunities remain for further research and therapeutic development.Key words:Acquired hypogonadotropic hypogonadism, thalassemia, iron overload, liver disease.

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