High Transferrin Saturation Is Associated with Lower Monocytic Ferritin Heavy Chain Expression in Sickle Cell Anemia Patients

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 4058-4058
Author(s):  
Kleber Yotsumoto Fertrin ◽  
Carolina Lanaro ◽  
Carla Fernanda Franco-Penteado ◽  
Dulcinéia Martins Albuquerque ◽  
Betania Lucena Hatzlhofer ◽  
...  
Keyword(s):  
Iron Overload ◽  
Sickle Cell ◽  
Serum Ferritin ◽  
Iron Metabolism ◽  
Sickle Cell Anemia ◽  
Transferrin Saturation ◽  
C Reactive Protein ◽  
Iron Storage ◽  
Reactive Protein ◽  
Ferroxidase Activity

Abstract The pathophysiology of sickle cell anemia (SCA) involves hemolysis, vaso-occlusion and a chronic inflammatory state. Iron overload secondary to blood transfusions is a frequent complication in these patients, but cannot be adequately estimated by serum ferritin levels, because ferritin is also an acute phase reactant. Although excess iron elevates both ferritin levels and transferrin saturation (TSAT) in SCA patients, there is notorious discrepancy between these parameters. Ferritin is composed of heavy (FHC) and light chains (FLC), and ferroxidase activity by FHC is an important cytoprotective mechanism against redox-iron, a product of heme breakdown and largely present in overt iron overload. Previous studies have shown that overexpression of FHC in sickle cell mice prevented free hemoglobin-induced vaso-occlusion. Since ferritin is also highly expressed in circulating monocytes, and these cells have been shown to interact with other cellular types in the sickle cell vaso-occlusive process, we aimed to characterize ferritin chains in monocytes and investigate the relationship with biomarkers of iron metabolism, inflammation and hemolysis. Peripheral blood monocytes from sixteen adult sickle cell anemia patients in steady state were isolated using a double Ficoll-Percoll density gradient to separate monocytes from neutrophils and lymphocytes. FHC, FLC, TLR4 (toll-like receptor 4), and SLC40A1(ferroportin) gene expressions were determined by RT-qPCR. Blood samples were also collected to determine serum ferritin, iron, and TSAT, and plasma levels of lactate dehydrogenase, soluble transferrin receptor, erythropoietin, and C reactive protein. We found that the expression of TLR4, a receptor known to be activated by heme, correlated with FLC, but not FHC expression. Higher TLR4 expression was also associated with higher serum iron, but not with ferritin, TSAT, or LDH. Interestingly, we did not find a correlation between C reactive protein levels and ferritin in this group of patients. As expected, the expressions of both ferritin chains were correlated with each other (P=0.027, r=0.55), but we found the strongest correlation between FHC and TSAT (P=0.0008, r=-0.652). Patients with a TSAT over 40% had significantly lower expression of monocytic FTH (P=0.003). This suggests that either excessive iron can lead to FHC downregulation in monocytes, or that a decrease in monocytic ferritin ferroxidase activity in some SCA patients may impair safe iron storage in ferritin and contribute to the development of higher TSAT, independently from ferritin levels. Our data support that human monocyte regulation of ferritin chains in SCA patients mirrors what has been described in hepatic cells in a sickle cell mouse model. Patients with increased TSAT may be relatively deprived of the cytoprotective ferroxidase activity of FHC, and a relationship between FHC deficiency and complications in SCA remains to be investigated. Further studies should also address whether FHC in monocytes influences cell adhesion, thus supporting an important role for iron trafficking in cells involved in sickle cell vaso-occlusion, and corroborating other studies associating organ damage in SCA with iron metabolism dysregulation. Disclosures No relevant conflicts of interest to declare.

Safety and Efficacy of High Dose Intravenous Desferoxamine for Reduction of Iron Overload Due to Chronic Transfusion in Sickle Cell Patients.

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 1430-1430
Author(s):  
Ram Kalpatthi ◽  
Brittany Peters ◽  
David Holloman ◽  
Elizabeth Rackoffe ◽  
Deborah Disco ◽  
...  
Keyword(s):  
Serum Creatinine ◽  
Iron Overload ◽  
Sickle Cell ◽  
Serum Ferritin ◽  
Liver Tissue ◽  
Iron Concentration ◽  
P Value ◽  
High Dose ◽  
Liver Iron ◽  
Iron Storage

Abstract Background: Patients with sickle cell disease (SCD) receiving chronic blood transfusions are at risk of developing iron overload and organ toxicity. Chelation therapy with either subcutaneous (SQ) desferoxamine (DFO) or oral deferasirox is effective in preventing and reducing iron overload but poses significant challenges with patient compliance. Intravenous (IV) infusions of high dose DFO (HDD) have been utilized in non compliant patients with heavy iron overload in small case series. We review our experience of high dose IV DFO in a large cohort of SCD patients with significant iron overload who are non compliant with SQ DFO. Methods: The medical records of SCD patients who received HDD in our center between 1993 and 2004 were reviewed. All of them were on chronic transfusion, had significant iron overload defined by serum ferritin > 1500 and/or liver iron concentration (LIC) more than 10 μg/g of liver tissue and were non-compliant with SQ DFO. All patients underwent annual ophthalmologic, hearing, pulmonary and cardiac evaluation. Demographic data, treatment details, serum ferritin levels, liver iron concentration (LIC), liver enzymes, renal function tests, audiogram and other relevant clinical data were collected. Results: There were 27 patients (19 males, 8 females), 19 patients were on transfusion for history of cerebrovascular accident, 5 for abnormal transcranial Doppler flow velocity, 2 for transient ischemic attack and one for recurrent pain crises. All continued to receive packed red blood cell transfusions aimed to keep HbS levels below 30 or 50% during this time. They were treated in-hospital with DFO 15 mg/kg/hr IV for 48 hrs every 2 weeks (20 patients), 3 weeks (4 patients) and 4 weeks (3 patients). The mean age at start of high dose regimen was 14.6 years (range 9–27 years). The mean duration of HDD treatment was 8.9 months (range 3–49 months). Fourteen patients had LIC determined by liver biopsy. Significant reductions in LIC were observed after HD (table I). This was more pronounced in patients who had higher LIC and received at least 6 months of HDD. Histological examination of liver biopsies revealed a decrease in the grade of liver iron storage. Four patients had portal triaditis initially which resolved after starting HDD therapy. Also there was significant improvement in liver enzymes (ALT, AST) after HDD. There was a trend in decreasing ferritin levels after HDD but this did not achieve statistical significance. All patients tolerated HDD without any major reactions. No audiologic or ophthalmologic toxicity or acute or chronic pulmonary complications were observed. Blood urea nitrogen remained normal in all patients after HDD but there was mild increase in serum creatinine. One patient had high serum creatinine (1.2 mg/dL) after two doses HDD. This patient had focal segmental glomeurosclerosis which was most probably the cause for the rise in creatinine. There was no significant increase in serum creatinine in our series when this patient was excluded. Conclusions: In our cohort of SCD patients we observed a significant decrease in liver iron burden with high dose IV DFO. Our patients tolerated the therapy well without any major toxicity. This regimen is safe and may be an option for poorly compliant patients with significant iron overload. In addition, combination of this regimen with oral iron chelators may be of benefit to patients with significant iron overload and organ dysfunction. Table 1: Laboratory characteristics of sickle cell patients before and after high dose IV DFO Parameter No. of Patients Mean (SD) prior to HDD Mean (SD)after HDD p Value* * Changes in mean levels analyzed using two-tailed Paired T Test with significant p value ≤ 0.05. SD – Standard deviation + See text Liver iron (μg/g of liver tissue ) 14 16864 (10903) 12681 (8298) 0.04 Liver iron min of 6 months of HDD (μg/g of liver tissue ) 8 18677 (8319) 9362 (4521) 0.01 Liver iron >10 mg & minimum 6 months of HDD (μg/g of liver tissue) 7 21181 (7054) 10092 (4443) 0.01 Grade of liver iron storage 14 3.57 (0.9) 3.07 (1) 0.05 Serum Ferritin (ng/mL) 27 3842 (2619) 3238 (1780) 0.06 Serum AST (IU/L) 27 54.1 (27.2) 44.6 (17.6) 0.04 Serum ALT (IU/L) 27 39.2 (36) 27.5 (14.2) 0.01 Blood urea nitrogen (mg/dL) 27 8.9 (2.9) 9.5 (4.3) 0.20 Serum Creatinine (mg/dL)+ 26 0.50 (0.1) 0.55 (0.2) 0.07

scholarly journals Effect of Gum Arabic (Acacia Senegal )on C-reactive protein level among Sickle Cell Anemia patients

2020 ◽  
Author(s):  
Lamis AbdelGadir Kaddam ◽  
Anas Suliman Kaddam
Keyword(s):  
Sickle Cell ◽  
Sickle Cell Anemia ◽  
Protein Level ◽  
Daily Intake ◽  
Gum Arabic ◽  
Fetal Hemoglobin ◽  
C Reactive Protein ◽  
Acacia Senegal ◽  
Reactive Protein ◽  
Anti Inflammatory

Abstract Objectives: Inflammation is ongoing process among sickle cell anemia even during steady state. C reactive protein (CRP) is cardinal marker that utilized widely as inflammatory indicator. Gum Arabic (GA) is gummy exudates from Acacia Senegal tree. Fermentation by colonic bacteria increases serum butyrate concentrations, so considered as prebiotic agent. Gum Arabic (GA) has anti-inflammatory activity through butyrate. Earlier we proved that regular intake of GA increased fetal hemoglobin and anti-oxidant capacity most likely through raised level of butyrate, which would ameliorate symptoms of sickle cell anemia. Best of our knowledge this is the first study conducted to investigate GA intake on inflammatory markers among sickle patients.Results : This was a retrospective study conducted on stored samples from trial of Gum Arabic and sickle cell anemia. Quantitative CRP was measured by Mindray BS 200 before and after Gum Arabic consumption for 12 weeks. Daily intake of GA significantly decreased C reactive protein level (P.V=001) (95% CI, 0.943 -3.098). No correlation between CRP and age, fetal hemoglobin, hemolysis markers and white blood cells. Our findings revealed novel effect of GA as anti-inflammatory agent can be consumed as natural dietary supplement to modulate disease severity and downregulate inflammatory process.Trial registration: ClinicalTrials.gov Identifier: NCT02467257. Registered 3rd June 2015

Effect of Gum Arabic (Acacia Senegal )on C-reactive protein level among Sickle Cell Anemia patients

2020 ◽  
Author(s):  
Lamis AbdelGadir Kaddam ◽  
Anas Suliman Kaddam
Keyword(s):  
Sickle Cell ◽  
Sickle Cell Anemia ◽  
Protein Level ◽  
Daily Intake ◽  
Gum Arabic ◽  
Fetal Hemoglobin ◽  
C Reactive Protein ◽  
Acacia Senegal ◽  
Reactive Protein ◽  
Anti Inflammatory

Abstract Objectives: Inflammation is ongoing process among sickle cell anemia even during steady state. C reactive protein (CRP) is cardinal marker that utilized widely as inflammatory indicator. Gum Arabic (GA) is gummy exudates from Acacia Senegal tree. Fermentation by colonic bacteria increases serum butyrate concentrations, so considered as prebiotic agent. Gum Arabic (GA) has anti-inflammatory activity through butyrate. Earlier we proved that regular intake of GA increased fetal hemoglobin and anti-oxidant capacity most likely through raised level of butyrate, which would ameliorate symptoms of sickle cell anemia. Best of our knowledge this is the first study conducted to investigate GA intake on inflammatory markers among sickle patients. Results : This was a retrospective study conducted on stored samples from trial of Gum Arabic and sickle cell anemia. Quantitative CRP was measured by Mindray BS 200 before and after Gum Arabic consumption for 12 weeks. Daily intake of GA significantly decreased C reactive protein level (P.V=001) (95% CI, 0.943 -3.098). No correlation between CRP and age, fetal hemoglobin, hemolysis markers and white blood cells. Our findings revealed novel effect of GA as anti-inflammatory agent can be consumed as natural dietary supplement to modulate disease severity and downregulate inflammatory process.

MO560IS SERUM ERYTHROPOIETIN CORRELATED WITH IRON METABOLISM AND INFLAMMATION IN NON-DIALYSIS CHRONIC KIDNEY DISEASE PATIENTS WITH ANEMIA?

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
Cristina-Stela Capusa ◽  
Ana-Maria Mehedinti ◽  
Ana Stanciu ◽  
Gabriela-Adriana Talimba ◽  
Liliana Viasu ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Bone Marrow ◽  
Kidney Disease ◽  
Serum Albumin ◽  
Serum Ferritin ◽  
Iron Metabolism ◽  
Mean Corpuscular Hemoglobin ◽  
C Reactive Protein ◽  
Reactive Protein ◽  
Serum Hepcidin

Abstract Background and Aims Both the relative erythropoietin (Epo) deficiency and its relationship with serum hemoglobin (Hb) are widely postulated in chronic kidney disease (CKD), but the influence of chronic inflammation and iron status on serum Epo levels is still a matter of debate, with yet divergent reported results. Therefore, we aimed to assess the determinants of serum Epo in non-dialysis CKD patients. Method Fifty-two adults with CKD and anemia (defined as Hb <12g/dL), in stable clinical condition, never treated with erythropoiesis-stimulating agents (ESA) entered this cross-sectional, single-center study. Diabetes mellitus, active infectious and inflammatory diseases, malignancy, anemia of other causes than CKD, current immunosuppressive therapy, iron supplementation and blood transfusions in the previous six months were exclusion criteria. The subjects were mostly men (56%), elderly (two thirds over 60 years), with advanced CKD [71% in CKD stages G4-G5, median estimated glomerular filtration rate – eGFR 14.5 (95%CI 16 to 25) mL/min], moderate anemia [Hb 9.8 (95%CI 9.2 to 9.9) g/dL], and mild to moderate inflammation [C-reactive protein 6 (95%CI 9.2 to 18.4) mg/L]. Serum Epo was assessed by ELISA (Abcam® 119522). Complete blood count, reticulocyte index, peripheral blood smear, bone marrow aspiration (Perls’ stain), serum ferritin, and transferrin saturation, were used to investigate anemia and iron metabolism. Parameters of kidney disease (CKD etiology, eGFR and proteinuria), demographic data (age, gender), C-reactive protein, serum albumin, and serum hepcidin-25 (Hep-25, Bachem® commercial ELISA kit) were also analyzed. Results The median serum Epo of the whole cohort was 4.8 (95%CI 5.1 to 9.9) mU/mL. According to median Epo, subjects were clustered in Group 1 (below median, G1) and Group 2 (above median, G2). Estimated GFR and serum Hep-25 were lower in G1 than in G2 [10.6 (95%CI 9.7 to 20.8) vs. 26 (95%CI 19.1 to 32.8) mL/min, p=0.004, and 62.6 (95%CI 51.0 to 85.1) vs. 95.4 (95%CI 77.0 to 108.5) ng/mL, p=0.03, respectively]. All the other investigated parameters were similar in the two groups. In bivariate analysis (Spearman rank correlation), serum Epo was positively associated only with eGFR (rs=0.40, p=0.003). Marginal associations with the percentage of bone marrow sideroblasts, as marker of the iron available for erythropoiesis (rs=0.25, p=0.08), erythrocyte mean corpuscular hemoglobin concentration (rs=−0.26, p=0.07), and reticulocyte index (rs=0.24, p=0.09) were observed. Conversely, serum Epo was not related to hemoglobin, indices of iron stores (e.g. serum ferritin and iron content in bone marrow macrophages), inflammation and nutritional status (e.g. C-reactive protein and serum albumin). In a model of multiple linear regression which explained 14% of serum Epo variation, eGFR was the only determinant: Beta 0.14 (95%CI 0.05 to 0.23), p=0.004. Also, a binary logistic multiple regression model predicting serum Epo lower or higher than the median retained the eGFR as an independent predictor, while serum hepcidin showed only borderline significance: Conclusion Kidney function is the main determinant of endogenous erythropoietin level in moderately anemic patients with advanced CKD, ESA or iron naive, while serum hepcidin-25 seems to exert a limited influence.

From Renal Siderosis Due to Perpetual Hemosiderinuria to Possible Liver Overload Due to Extravascular Hemolysis: Changes in Iron Metabolism in Paroxysmal Nocturnal Hemoglobinuria (PNH) Patients On Eculizumab.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 4031-4031 ◽  
Author(s):  
Antonio M. Risitano ◽  
Elisa Seneca ◽  
Ludovica Marando ◽  
Massimo Imbriaco ◽  
Ernesto Soscia ◽  
...  
Keyword(s):  
Iron Overload ◽  
Serum Ferritin ◽  
Iron Metabolism ◽  
Renal Cortex ◽  
Transferrin Saturation ◽  
Iron Loss ◽  
Hepatic Iron ◽  
Intravascular Hemolysis ◽  
Hepatic Iron Overload ◽  
Spin Echo Sequence

Abstract Abstract 4031 Poster Board III-967 Iron metabolism in PNH patients is dominated by perpetual iron loss consequent to the chronic complement-mediated intravascular hemolysis; thus, they are prone to develop iron deficiency rather than iron overload, even in presence of large transfusional requirement. Eculizumab (Ecu) has proven effective for the treatment of intravascular hemolysis in PNH patients, resulting in reduction and even abolishment of transfusion requirement and improvement of signs and symptoms of intravascular hemolysis; however, Hb gain is heterogeneous among patients, in most cases due to residual C3-mediated extravascular hemolysis hampering Hb normalization. The goal of our study was to identify possible modifications in iron compartmentalization associated with Ecu treatment and possible clinical consequences. We evaluated iron metabolism in 5 untreated PNH patients and 23 who were receiving Ecu (of whom 4 have been also studied before treatment), combining biochemical parameters with a semiquantitative T2* MRI technology. MRI was performed using four gradient-echo sequences and one spin-echo sequence; signal intensity (SI) was measured on images obtained with each sequence by means of three regions of interest placed in the renal cortex, liver, spleen and at the level of the para-spinal muscle, resulting in a semiquantitative SI value (Grandon et al., Radiology 1994). Within the total patient cohort (regardless they were or were not on Ecu), there was a significant correlation between liver SI and serum ferritin (P<0.001), while kidney SI correlated with the presence of hemosiderinuria (HS, P<0.001). All untreated PNH patients showed similar MRI findings, with significant renal cortex siderosis and normal SI in liver and spleen. This was consistent with overt intravascular hemolysis, as confirmed by biochemical routine testing, and consequent perpetual hemosiderinuria; as expected, all these patients had abundant HS. In contrast, the 23 PNH patients on Ecu showed a distinct and heterogeneous pattern. All patients showed a normal renal SI, with the exception of 2 cases who have recently started Ecu and 2 experiencing Ecu breakthrough; these 4 patients had normal hepatic and splenic SI. All of them (but none of those with normal renal SI) had persistent HS, while only the latter 2 had increased LDH; we conclude that these 4 patients have had residual intravascular hemolysis, and that HS was more sensitive than LDH to identify recent history of intravascular hemolysis. In contrast, the majority of patients showed increased hepatic SI: we found 6 cases with moderate and 5 cases with severe iron overload; in some patients, high hepatic SI was associated with increased SI in the spleen. The 4 patients evaluated before and during treatment showed pre-treatment renal siderosis which progressively disappeared after months of Ecu therapy; in 2 of them, who had a longer exposition to Ecu, moderate hepatic iron overload was demonstrated. Hepatic SI significantly correlated with serum ferritin (P<0.05), but not with transferrin saturation nor with LDH. Iron overload was predictable as a result of persistent transfusional need only in two patients with partial response to Ecu; however, within the whole cohort, patients with suboptimal hematological response (i.e., those with persistent Hb<11) were more likely to develop severe hepatic iron overload (P=0.02). Thus, we hypothesized that iron overload in these patients may be pathophysiilogically linked to persistent extravascular hemolysis; we found a direct correlation between liver SI and both % of C3+ PNH RBCs (P=0.02) and absolute reticulocyte count (P=0.02), which were considered markers of extravascular hemolysis (Risitano et al, Blood 2009). In conclusion, we show by T2* RMI that untreated PNH patients have significant renal siderosis, which tends to disappear during Ecu treatment as a result of the blockade of intravascular hemolysis. However, such blockade of urinary iron loss may render PNH patients susceptible to liver iron overload resulting from transfusions, as well as from residual extravascular hemolysis. While is still not clear the proportion of patients developing clinically significant iron overload requiring specific treatment, we provide evidence that iron metabolism substantially changes during eculizumab treatment, and C3-mediated extravascular hemolysis may play a major role in this process. Disclosures: Risitano: Alexion Pharmaceuticals: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding.

scholarly journals Assessing the Association between Serum Ferritin, Transferrin Saturation, and C-Reactive Protein in Northern Territory Indigenous Australian Patients with High Serum Ferritin on Maintenance Haemodialysis

2017 ◽  
Vol 2017 ◽  
pp. 1-8
Author(s):  
Sandawana William Majoni ◽  
Paul D. Lawton ◽  
Federica Barzi ◽  
Alan Cass ◽  
Jaquelyne T. Hughes
Keyword(s):  
Serum Ferritin ◽  
Iron Status ◽  
Transferrin Saturation ◽  
Northern Territory ◽  
High Serum ◽  
C Reactive Protein ◽  
Indigenous Australian ◽  
Maintenance Haemodialysis ◽  
Reactive Protein ◽  
Markers Of Inflammation

Objective. To determine the significance of high serum ferritin observed in Indigenous Australian patients on maintenance haemodialysis in the Northern Territory, we assessed the relationship between ferritin and transferrin saturation (TSAT) as measures of iron status and ferritin and C-reactive protein (CRP) as markers of inflammation. Methods. We performed a retrospective cohort analysis of data from adult patients (≥18 years) on maintenance haemodialysis (>3 months) from 2004 to 2011. Results. There were 1568 patients. The mean age was 53.9 (11.9) years. 1244 (79.3%) were Indigenous. 44.2% (n=693) were male. Indigenous patients were younger (mean age [52.3 (11.1) versus 57.4 (15.2), p<0.001]) and had higher CRP [14.7 mg/l (7–35) versus 5.9 mg/l (1.9–17.5), p<0.001], higher median serum ferritin [1069 µg/l (668–1522) versus 794.9 µg/l (558.5–1252.0), p<0.001], but similar transferrin saturation [26% (19–37) versus 28% (20–38), p=0.516]. We observed a small positive correlation between ferritin and TSAT (r2=0.11, p<0.001), no correlation between ferritin and CRP (r2 = 0.001, p<0.001), and positive association between high serum ferritin and TSAT (p<0.001), Indigenous ethnicity (p<0.001), urea reduction ratio (p=0.001), and gender (p<0.001) after adjustment in mixed regression analysis. Conclusion. Serum ferritin and TSAT may inadequately reflect iron status in this population. The high ferritin was poorly explained by inflammation.

scholarly journals Inflammation, iron and vitamin D metabolism in different cardiomyopathy aetiologies

Pteridines ◽  
2020 ◽  
Vol 31 (1) ◽  
pp. 28-37
Author(s):  
Lukas Lanser ◽  
Nada Nemati ◽  
Markus Seifert ◽  
Dietmar Fuchs ◽  
Günter Weiss ◽  
...  
Keyword(s):  
Vitamin D ◽  
Iron Metabolism ◽  
Immune Activation ◽  
Transferrin Saturation ◽  
C Reactive Protein ◽  
Inflammatory Cardiomyopathy ◽  
Vitamin D Metabolism ◽  
Protein Levels ◽  
Reactive Protein ◽  
Ischaemic Cardiomyopathy

AbstractImmune activation coincides with disturbances in iron and vitamin D metabolism in patients with cardiomyopathy. In this study, we investigated whether there are differences regarding immune activation, iron and vitamin D metabolism between the different cardiomyopathy aetiologies.Patients and methods: Parameters of iron metabolism (haemoglobin, iron, transferrin, transferrin saturation, ferritin, hepcidin), vitamin D metabolism (Ct-FGF23, parathormone, phosphate, vitamin D) and immune activation (C-reactive protein and neopterin) were determined in 149 patients (98 men, 51 women) with non-ischaemic cardiomyopathy.Results: Patients with amyloid cardiomyopathy presented with higher neopterin, ferritin and hepcidin levels than other cardiomyopathy aetiologies. Furthermore, they showed the highest rate of cardiovascular events. C-reactive protein levels were significantly higher in patients with inflammatory cardiomyopathy. Patients with virus positive cardiomyopathy presented with significantly higher ferritin and Ct-FGF23 levels compared to patients with virus negative inflammatory cardiomyopathy.Conclusion: This study indicates that there are some differences regarding the extent of immune activation and inflammation as well as alterations in iron metabolism disorders between different cardiomyopathy aetiologies. Further studies with larger patient cohorts are needed to investigate these findings more precisely.

Deferasirox for the Treatment of Transfusional Iron Overload in Sickle Cell Anemia. Preliminary Results

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 2879-2879
Author(s):  
Rodolfo D Cancado ◽  
Maria Cristina A Olivato ◽  
Paula Bruniera ◽  
Carlos Chiattone
Keyword(s):  
Serum Creatinine ◽  
Iron Overload ◽  
Sickle Cell ◽  
Serum Ferritin ◽  
Sickle Cell Anemia ◽  
The Body ◽  
Once Daily ◽  
Body Iron ◽  
Endocrine Organs ◽  
The Impact

Abstract The majority of patients with sickle cell anaemia have received repeated blood transfusions by adulthood. Because the body has no physiological mechanism to actively excrete the excess of iron, chelation therapy is important for the management of iron overload and its complications, including iron deposition into the liver, heart and endocrine organs, eventual death. While studies are limited, progressive iron loading and subsequent tissue injury in sickle cell disease appears similar to other transfused populations. Deferasirox (Exjade, ICL670) is a once-daily, oral iron chelator that is approved for the first-line treatment of chronic transfusional iron overload. Its safety, tolerability and efficacy in reducing body iron burden have been demonstrated in patients with β-thalassaemia major and in other chronic transfusion-dependent anaemias. The objectives of this prospective, non-randomised, phase IV trial were to evaluate the iron overload status, before and after one year-treatment with deferasirox, using liver iron concentration (LIC) by MRI of the liver, MRI cardiac (Cardiac T2*), serum ferritin and the impact of deferasirox treatment on these measurements, and to evaluate the safety and tolerability of this drug. A total of 30 patients with sickle cell anemia and iron overload, defined as the use of ≥ 20 units of RBC units and/or two plasma ferritin levels ≥ 1000 mcg/L during the 6 months preceding enrollment, received starting dose of 20mg/kg/day of deferasirox. Efficacy was assessed monthly by measuring change from baseline in serum ferritin levels. Safety was evaluated on a monthly basis according to the incidence and type of adverse events and measurement of laboratory parameters, including serum creatinine and liver enzyme levels. Mean (range) age 26.4 ± 12.3y (9–49), 83% female, 93% afrodescendent, 60% on regular blood transfusion, mean deferasirox exposure 30.1 ± 5.6 weeks (16–39), mean MRI hepatic (LIC, μmol/g) 233.0 ± 98.8 (45 – 350), mean MRI cardiac (Cardiac T2*, ms) 41.20 ± 5.46 (27.52 – 51.19). Median ± SD and mean (range) serum ferritin level (mcg/L) at baseline and 6 months varied from 2315.5 ± 1083.9 to 2062.5 ± 1320.8 (p=0.032) and 2012.0 (1013–6074) to 1654.0 (688–6729), respectively. The proportion of patients with serum ferritin levels &lt; 2000, 2000- &lt;3000 and ≥ 3000 mcg/L from baseline to 6 months by percentage of patients changed from 50% to 60%, 26.7% to 26.7% and 23.3% to 13.3%, respectively. The most common drug-related AEs were mild, transient diarrhea (23.3%), headache (20.0%) and nausea (16.7%). Maculo-papular skin rash and serum creatinine increases upper limit of normal were observed in 2 (6.7%) patients. No patient experienced progressive increases in serum creatinine or renal failure. Our preliminary data, over 6-month-period of treatment, confirms that deferasirox is effective and generally well tolerated in pediatric and adult patients, and appears to have similar efficacy to deferoxamine in reducing body iron burden in transfused patients with sickle cell anemia. The availability of deferasirox as a once-daily, oral alternative would potentially facilitate improved compliance, and thereby reduce morbidity and mortality from iron overload.

scholarly journals Burden of iron overload among non-chronically blood transfused preschool children with sickle cell anaemia

2021 ◽  
Vol 21 (2) ◽  
pp. 753-758
Author(s):  
Akodu Samuel Olufemi ◽  
Adekanmbi Abiodun Folashade ◽  
Ogunlesi Tinuade Adetutu
Keyword(s):  
Preschool Children ◽  
Blood Transfusion ◽  
Iron Overload ◽  
Sickle Cell ◽  
Serum Ferritin ◽  
Serum Ferritin Level ◽  
Sickle Cell Anaemia ◽  
Ferritin Level ◽  
Genetic Disorder ◽  
Transferrin Saturation

Background: Sickle cell disease is the commonest genetic disorder of haemoglobin due to inheritance of mutant haemo- globin genes from both parents. The disorder is characterized by chronic haemolysis which results in increased availability of iron from red blood cell destructions. Objective: To determine the prevalence of iron overload among non-chronically blood transfused preschool children with sickle cell anaemia. Methods: Serum ferritin was assayed and transferrin saturation derived in 97 steady state sickle cell anaemia children. Ele- vated iron stores were defined as serum ferritin level >300ng/ml, and transferrin saturation >45%. . Results: Serum ferritin level was greater than 300 mg/ml in 14 (14.4%) subjects and transferrin saturation >45% in six (6.2%) subjects with sickle cell anaemia. The prevalence of iron overload was 20.6%. The prevalence of iron overload was higher among subjects in older age group, female, with history of blood transfusion, and with single blood transfusion ses- sion. Conclusion: Iron overload is prevalent in older children; the number of blood transfusion sessions notwithstanding. Regu- lar assessment of serum ferritin is recommended. Keywords: Sickle cell anemia; iron overload; serum ferritin; transferrin saturation; elevated iron.

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