Iron Trafficking and Distribution in Transfusional Overload: Insights From Comparing Diamond Blackfan Anemia with Sickle Cell Disease and Thalassemia

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 995-995 ◽  
Author(s):  
John B. Porter ◽  
Patrick B Walter ◽  
Lynne D Neumayr ◽  
Patricia Evans ◽  
Marcela G Weyhmiller ◽  
...  
Keyword(s):  
Sickle Cell Disease ◽  
Iron Overload ◽  
Sickle Cell ◽  
Research Funding ◽  
Hepatic Iron ◽  
Iron Loading ◽  
Cell Disease ◽  
Ineffective Erythropoiesis ◽  
Iron Distribution ◽  
Diamond Blackfan Anemia

Abstract Abstract 995 Background: β-thalassemia major (TM) is the paradigm for chronic transfusional iron overload, in which the extra-hepatic organ failure is best described. In Sickle Cell Disease (SCD), these consequences appear later and at a lower frequency. In chronically transfused Diamond Blackfan Anemia (DBA), extra-hepatic iron overload, although less well documented, appears to occur early and at high frequency. A Multicenter Study of Iron Overload (MCSIO) aims to explore how key candidate factors affect iron distribution; including inflammation, ineffective erythropoiesis, level of iron overload, and hepcidin synthesis. Plasma non-transferrin bound iron (NTBI) could be a key mechanism by which iron is delivered to tissues and may determine the propensity for extra-hepatic iron distribution. Here we focus on how markers of ineffective erythropoiesis (IE) and erythron expansion impact iron distribution, with particular reference to NTBI and iron distribution determined by MRI. Methods: Iron-overloaded patients (5 TM, 5 SCD, and 5 DBA) with ferritin > 1500 g/dl or LIC > 7 mg/g dry wt, age ≥16, age 0 to 9 at initiation of transfusion and 10 to 20 years of transfusion exposure were enrolled from 3 sites in the US and Europe. 5 non-transfused healthy controls were also enrolled. A detailed medical, transfusion and chelation history were obtained with standardized MRI evaluations for hepatic, cardiac, and pituitary iron deposition. Fasting, early morning blood samples were obtained one day prior to transfusion. Chelation was held for 72 hours prior to each sample. Results: Results are shown in the table as median values. DBA patients had the highest NTBI prior to transfusion despite having the lowest ferritin and LIC levels. GDF15 levels were highest in TM, with similar levels in SCD and DBA. EPO levels were nearly two orders of magnitude higher in DBA than TM or SCD. DBA patients also had the highest median cardiac R2*; two patients showing values above the control range. Whereas the median pituitary R2 in DBA was not above control, two of the patients had the highest R2 values, suggesting heavy iron deposition. EPO values in DBA are nearly two orders of magnitude higher that in SCD or TM despite similar pre-transfusion Hb values. GDF15 values are approximately three times controls, while soluble transferrin receptors (sTfR) values are almost undetectable. With SCD, no patients had increased cardiac iron loading, despite median SF and LIC being the highest in this group. Surprisingly all SCD patients had pituitary R2 values above the upper limit of normal. 1 TM patient had increased cardiac R2* whereas three had increased pituitary iron. In TM, NTBI was strongly correlated with GDF15 (Pearson's Rho=0.93) but in DBA, GDF15 was inversely correlated with NTBI (-.95). Conclusions: High GDF15 levels have been reported in conditions associated with IE, such as TM, but not in DBA. GDF15 reputedly suppresses hepcidin synthesis, thereby increasing iron absorption and potentially NTBI levels. The increased GDF15 in DBA, while sTfr remain less than controls, suggests that erythropoietic precursors do not reach the stage where sTfr are expressed and that this occurs at a later differentiation stage than GDF15. Increasing NTBI in TM with increasing GDF15 is consistent with IE contributing to NTBI formation, but the lack of this relationship in DBA suggest another mechanism for high NTBI. As the erythron is destroyed at a pre-hemoglobinised stage in DBA, IE would not contribute directly to NTBI formation. However, the extremely high EPO levels in DBA may inhibit hepcidin synthesis, as in other conditions, thereby increasing NTBI. This in turn may account for the extra-hepatic iron distribution demonstrated by MRI in DBA. The increased pituitary iron without cardiac loading in the heavily loaded SCD patients suggests that with prolonged exposure to heavy iron overload, the pituitary iron loading may be the first indicator of extra-hepatic deposition. Disclosures: Porter: Novartis: Consultancy, Research Funding. Walter:Novartis: Research Funding. Harmatz:Novartis: Research Funding; Ferrokin: Research Funding. Wood:Ferrokin Biosciences: Consultancy; Shire: Consultancy; Apotex: Consultancy, Honoraria; Novartis: Honoraria, Research Funding. Vichinsky:Novartis: Consultancy, Research Funding; ApoPharma: Consultancy, Research Funding; ARUP Research lab: Research Funding.

Consequences and management of iron overload in sickle cell disease

Hematology ◽  
2013 ◽  
Vol 2013 (1) ◽  
pp. 447-456 ◽  
Author(s):  
John Porter ◽  
Maciej Garbowski
Keyword(s):  
Sickle Cell Disease ◽  
Blood Transfusion ◽  
Iron Overload ◽  
Sickle Cell ◽  
Iron Concentration ◽  
Thalassemia Major ◽  
Iron Loading ◽  
Cell Disease ◽  
Liver Iron Concentration ◽  
Liver Iron

Abstract The aims of this review are to highlight the mechanisms and consequences of iron distribution that are most relevant to transfused sickle cell disease (SCD) patients and to address the particular challenges in the monitoring and treatment of iron overload. In contrast to many inherited anemias, in SCD, iron overload does not occur without blood transfusion. The rate of iron loading in SCD depends on the blood transfusion regime: with simple hypertransfusion regimes, rates approximate to thalassemia major, but iron loading can be minimal with automated erythrocyte apheresis. The consequences of transfusional iron overload largely reflect the distribution of storage iron. In SCD, a lower proportion of transfused iron distributes extrahepatically and occurs later than in thalassemia major, so complications of iron overload to the heart and endocrine system are less common. We discuss the mechanisms by which these differences may be mediated. Treatment with iron chelation and monitoring of transfusional iron overload in SCD aim principally at controlling liver iron, thereby reducing the risk of cirrhosis and hepatocellular carcinoma. Monitoring of liver iron concentration pretreatment and in response to chelation can be estimated using serum ferritin, but noninvasive measurement of liver iron concentration using validated and widely available MRI techniques reduces the risk of under- or overtreatment. The optimal use of chelation regimes to achieve these goals is described.

scholarly journals Assessment of Iron Overload Impact on QTc Interval in Patients with Sickle Cell Disease

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 3673-3673
Author(s):  
Gilbert Bader ◽  
Gregory J. Kato ◽  
Suvankar Majumdar ◽  
James Pollard ◽  
Jarrod Knudson ◽  
...  
Keyword(s):  
Sickle Cell Disease ◽  
Iron Overload ◽  
Sickle Cell ◽  
Research Funding ◽  
Iron Toxicity ◽  
Conduction Delay ◽  
P Value ◽  
Qtc Interval ◽  
Cell Disease ◽  
Qtc Prolongation

Abstract Ischemic injuries and subsequent degenerative myocardial and conduction system abnormalities occur in patients with sickle cell disease (SCD). This may lead to conduction and repolarization delays reflected as QTc prolongation. Patients with SCD have increased risk of cardiac death, the basis of which remains uncertain. QTc prolongation may be a contributing factor. We decided to examine factors that can potentiate QTc prolongation in this population. In particular, we studied effect of iron overload estimated by serum Ferritin level on QTc. We performed a cross-sectional study in SCD patients older than 18 years, in steady state, followed in our clinic. Patients with acute illness or vaso-occlusive crisis in prior 2 weeks, patients with bundle branch block, pacemaker or arrhythmia and patients unable to give consent were excluded. Prolonged QTC was defined as >450 and >460 ms in men and women respectively. Patients were divided into 3 groups corresponding to mild, moderate and severe iron overload with Ferritin < 1000, between 1000 and 3000 and > 3000 ng/mL respectively. QTc was prolonged in 25/177 patients (14%). Those were older (p=0.041), had lower hemoglobin (Hb) (p<0.001) and higher Ferritin (p=0.019). Their mean age was 33.8 years, Hb 8.26 g/dL and Ferritin 3167 ng/mL compared to 29.2, 9.58 and 1735 respectively in patients with normal QTc. Twenty eight % of patients with prolonged QTc had comorbidities compared to 9% of patients with normal QTc (p=0.004). There was no difference between the 2 groups regarding gender, weight, blood pressure, Lactate dehydrogenase, electrolytes, Reticulocytes count or use of medications known to prolong QTc. Mean QTC was 429, 438 and 440 ms in groups 1,2 and 3 respectively (p=0.013). Linear regression analysis showed that QTc is expected to be longer in groups 2 and 3 compared to group 1. We also estimated QTc prolongation corresponding to 500 unit increment in Ferritin. QTc is expected to get prolonged by 0.83 ms for each 500 unit increment of Ferritin with p value of 0.028 in unadjusted model and by 0.79 ms with p value of 0.035 and 0.67 ms with p value of 0.085 in models where age and comorbidities were adjusted for respectively. Hb was found to be inversely correlated with Ferritin. Correlation coefficient was -0.39 with p value < 0.001. Although there was no significant correlation between Ferritin and JTc, analysis showed that QRS is expected to increase by 0.33 ms for each 500 unit increment in Ferritin with p value of 0.022. Comorbidities including diabetes mellitus, kidney and heart disease are known independent factors that can cause QTC prolongation. QTc increases with age. However, this mainly applies to people older than 50 years (J Geriatric Cardiol 2016 Sep;13(9):740-8). We don't believe age is an independent QTc prolonging factor in our patients especially that mean age of patients with prolonged QTc was 33.87 years. Probably older patients had longer exposure to iron toxicity which may be the true contributing factor to QTc prolongation. Patients with prolonged QTc had lower Hb. However, no correlation was found between Hb and QTc in patients with anemia caused by conditions other than SCD (Chin Med J 2015 Dec 20;128(24):3385-6). In addition, major cause of tissue injury in SCD patients is intracellular polymerization of HbS. However, there is no correlation between Hb concentration and intracellular HbS polymer content (Blood 1998 Mar 1;91(5):1777-83). Thus, we don't think Hb is an independent QTc prolonging factor. Probably patients with lower Hb received more transfusions and subsequently had more pronounced iron overload which may be the direct contributing factor to QTc prolongation. The negative correlation between Hb and Ferritin supports our hypothesis. Thus, we think that the model where just comorbidities were adjusted for is the best to reflect the association between Ferritin and QTc. Iron overload reduces overshoot ( Circulation 1999 Aug 10;100(6):675-83) which will compromise propagation of cardiac impulse and result in conduction delay. Iron also leads to production of free radicals. That will cause chronic inflammation and fibrosis. We showed that QRS is expected to get prolonged with iron overload in SCD patients which is consistent with the physiology of iron toxicity. QTc prolongation seems to be associated with iron overload in SCD patients. Conduction delay manifested by prolonged QRS may be the main contributor rather than repolarization delay. Disclosures Bader: NIMHD: Research Funding. Majumdar:NIMHD: Research Funding. Maher:NIMHD: Research Funding.

scholarly journals Cardiac Iron Overload in Sickle Cell Disease: When to Screen and How to Intervene

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 528-528
Author(s):  
Amy Y Tang ◽  
Cassandra D Josephson ◽  
Kristina Lai ◽  
Peter A. Lane ◽  
Ross M. Fasano
Keyword(s):  
Risk Factors ◽  
Sickle Cell Disease ◽  
Iron Overload ◽  
Sickle Cell ◽  
Clinical Characteristics ◽  
Iron Loading ◽  
Cell Disease ◽  
Transfusion Therapy ◽  
Cardiac Iron ◽  
Cardiac Iron Overload

Abstract Background Iron overload is a recognized consequence of chronic transfusion therapy in patients with sickle cell disease (SCD), but most of the focus to date has been on the effects of increased liver iron concentration (LIC) with increasing transfusion burden. Even though there is a robust body of literature concerning cardiac iron overload (CIO) in patients with thalassemia major, there remains a paucity of data in how to detect and treat CIO in patients with SCD, particularly in the pediatric and young adult population. While CIO is seen less commonly in sickle cell disease than in thalassemia, patients with SCD remain at risk, with recent studies demonstrating an incidence of 2-5% of CIO in chronically transfused patients with SCD. We performed a retrospective chart review of patients with cardiac MRIs (cMRIs) and LICs by Ferriscan performed at our institution to identify risk factors for CIO, as well as to characterize institutional practice for assessing cardiac iron in the absence of defined practice guidelines. Methods We reviewed clinical characteristics of all patients with SCD who had cMRIs performed at Children's Healthcare of Atlanta between June 2012 and December 2017. We then queried our institutional sickle cell database for patients who were at least 3 years old in 2010, genotype SS or S Beta zero thalassemia, were on chronic transfusions for at least 5 years by 2017, and had not undergone a cMRI. Patients who were status post bone marrow transplant were excluded. For comparison of age, average ferritin, and transfusion duration, significance among means between patients with and without CIO was calculated using a two-tailed unpaired t-test. For comparison of LIC, significance among medians was calculated using the Mann Whitney test. A p value of <0.05 was considered significant. Statistical analyses were performed using Prism 6 (GraphPad Software, Inc.). Results Of 36 evaluable patients who had undergone cMRI, there were 11 with CIO, as defined by a T2* < 20ms. Clinical characteristics are shown in Figure 1. Patients were 7-28 years of age, and had received chronic transfusion therapy for a range of 22 months to 228 months. Between patients who did and did not have CIO, there was no significant difference in average 1-year ferritin level (6786 vs 6373 ng/mL, p=0.79), transfusion duration (103 vs 123 months, p=0.41), or age (15 vs 18 years, p=0.12). There was a higher median LIC by Ferriscan of > 43 mg/g in those with CIO vs 34 mg/g in those without CIO, although this was not statistically significant (Figure 1). Interestingly, CIO was seen as young as 7 years of age and after as little as 22 months of chronic transfusions, and with concurrent LIC values as low as 8.1 mg/g. Of the 11 patients with CIO, 6 had follow-up cMRI data available, and all 6 had normalization of cardiac iron (T2* > 20ms) on subsequent MRIs (Figure 2 and Table 2). There was 1 patient who did not have full transfusion and chelation history available for analysis. Of the remaining 5, 5/5 had increased or more aggressive chelation added, including 2 who were started on high-dose IV Desferal every 2 weeks; 3/5 also had partial manual exchange (PME) added to their chronic transfusion regimens. There were 80 patients who were on chronic transfusions but did not have a cMRI performed; as a group, they had a median LIC of 17 mg/g (range: 1.7 - >43 mg/g), an average 1-year ferritin of 3641 ng/mL (range: 520 - 8478 ng/mL), and had been on chronic transfusions for a mean of 87 months at time of Ferriscan study (range: 14 - 192 months). Overall, these patients had a lower transfusion burden than those who received cMRIs, but there were several in this group who had significant iron overload, including 10 who had LIC values of > 43mg/g. Conclusion CIO in SCD may be a more salient issue, and occur earlier, than previously described. We did not find a strong relationship between CIO and ferritin levels or LIC by Ferriscan, but we did find that CIO was reversible with more aggressive chelation or the addition of PME. While guidelines for monitoring for CIO in SCD are largely extrapolated from thalassemia data, the rate and physiology of iron loading may be completely different. Due to a paucity of information in this area, more studies are needed to guide screening and to fully assess risk factors that may put certain individuals more at risk for cardiac iron loading. Disclosures No relevant conflicts of interest to declare.

scholarly journals Sickle Cell Disease Promotes Dysregulation of Hepatic Iron Homeostasis By Regulating Hepcidin Expression

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 958-958
Author(s):  
Tirthadipa Pradhan ◽  
Prithu Sundd ◽  
Satdarshan Pal Monga ◽  
Mark T Gladwin ◽  
Gregory J Kato
Keyword(s):  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Liver Tissue ◽  
Research Funding ◽  
Iron Homeostasis ◽  
Iron Accumulation ◽  
Expression Level ◽  
Hepatic Iron ◽  
Cell Disease ◽  
Hepcidin Expression

Sickle cell disease (SCD) is an autosomal-recessive-genetic disorder that affects millions of people worldwide. Although hepatic crisis affects 10-40% of hospitalized SCD patients and can progress to fatal liver failure, the current treatment is primarily supportive and the molecular pathophysiology remains largely unknown. We found that transgenic, humanized SCD mice developed liver injury with age, manifested by increased inflammation, necrosis and hepatic iron accumulation. The presence of iron particles in SCD liver was confirmed by transmission electron micrograph (TEM) analysis and prussian blue staining which revealed increased iron accumulation in the central and midzonal region of the SCD liver tissue. An increase in aggregates of iron pigment reminiscent of hemosiderin-laden macrophages was also observed in SCD liver tissue. Interestingly, the SCD mice also showed significant enrichment of both hepatic (p=0.02) and serum iron (p=0.04) compared to control AS mice. We determined the expression level of genes commonly involved in iron homeostasis by RT-PCR. Interestingly, a significantly lower expression level of hepcidin transcripts was observed in the liver of SCD mice compared to control mice (AS) (p=0.01). In order to define the pathways controlling hepcidin transcription in SCD, we performed an RNA-seq analysis in the liver of SCD mice. Remarkably, our data showed significant misexpression of hypoxia signaling pathways. Further analysis revealed a significant increase in hypoxia-inducible factor (HIF)-2α levels in the liver of SCD mice by western blot. Reduced levels of Hepcidin were also confirmed in serum samples from SCD patients compared to controls. Work is currently underway to understand how HIF2α might hypothetically regulate hepcidin expression in the liver. This is particularly relevant because HIF2a translation is known to be regulated by iron through an iron response element at the 5' end of its transcript. In summary, our results reveal a significant defect in iron homeostasis in the liver of SCD mice, suggesting that impaired iron homeostasis may contribute to hepatobiliary injury in SCD independent of blood transfusions. Our study also highlights the importance of hepcidin as potential therapeutic target in regulation of hepatic injury in SCD. Disclosures Gladwin: Bayer Pharmaceuticals: Other: Co-investigator; United Therapeutics: Patents & Royalties: Co-inventor on an NIH government patent for the use of nitrite salts in cardiovascular diseases ; Globin Solutions, Inc: Patents & Royalties: Provisional patents for the use of recombinant neuroglobin and heme-based molecules as antidotes for CO poisoning. Kato:Novartis, Global Blood Therapeutics: Consultancy, Research Funding; Bayer: Research Funding.

scholarly journals Iron Overload Is Under-Recognized and Under-Treated in SCD: A Report from the Grndad Registry

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 158-158
Author(s):  
Matthew Sears ◽  
Sophie Lanzkron ◽  
Carolyn Hoppe ◽  
Joshua J. Field ◽  
Payal C Desai ◽  
...  
Keyword(s):  
Sickle Cell Disease ◽  
Iron Overload ◽  
Sickle Cell ◽  
Research Funding ◽  
Chelation Therapy ◽  
Ferritin Level ◽  
Research Network ◽  
Cell Disease ◽  
Liver Iron ◽  
High Iron

Abstract Background: Chronic transfusion therapy (CTT) is a mainstay of prophylactic management and treatment for adults and children with high risk Sickle Cell Disease (SCD). We estimate that 10-20% of all adults with SCD managed at our centers, especially those with homozygous HbSS disease, are on CTT, for long-term management of cerebral vasculopathy, significant end organ damage, or chronic pain. Iron overload is a common complication of CTT and for patients receiving intermittent transfusion to treat acute complications. Each unit of transfused blood introduces approximately 250 mg of iron into the bloodstream, and with it, increased oxidative stress (A. Remacha, et al., "Guidelines on haemovigilance of post-transfusional iron overload," Blood Transfusion, vol. 11, no. 1, pp. 128-139, 2013). High iron levels in the blood cumulatively lead to systemic iron deposition, particularly in the liver and heart, and untreated may lead to organ dysfunction or death. Patients with high iron levels should be put on iron chelation. Recent NHLBI guidelines suggest that patients on CTT be monitored for iron accumulation with quarterly ferritin levels, and annual or semiannual liver iron scans to assess hepatic iron burden, though the optimal frequency of these scans has not been established (B. P. Yawn, et al., "Management of Sickle Cell Disease: Summary of the 2014 Evidence-Based Report by Expert Panel Members," JAMA, vol. 10, no. 312, pp. 1033-1048, 2014). We examined iron overload, its frequency, severity, and management, in a modern population of adults with SCD enrolled in the multi-center prospective sickle cell registry, Globin Research Network of Data and Discovery (GRNDaD). Methods: GRNDaD is a multi-site registry of both adult and pediatric SCD patients, currently accruing at 5 urban sickle cell centers, in Baltimore MD, Cleveland OH, Milwaukee WI, Columbus OH, and Oakland CA. It currently contains prospective baseline and annual update information on nearly 500 people with SCD. Additionally, approximately 150 more patients have consented, with data entry pending. The dataset comprises demographics as well as baseline and yearly lab values, complications, procedures, treatment, and vaccination history for each patient. Among these data are ferritin levels, liver iron scan results, and chelation therapy information. We analyzed ferritin levels in people with SCD, relative to genotype, age, gender, treatment type, liver iron scan results, and chelation therapy history. Results: There were 402 adults (age≥18 years) in GRNDaD who had a non-crisis ferritin level from a routine follow-up visit. This included people with phenotypic homozygous SCD (HbSS, n=255 and Sβ0 thalassemia, N=13), variant SCD (HbSC, n=80, or Sβ+ thalassemia, n=37), and other or unknown genotypes (n=17, Table 1). Nearly 3 in 10 of all patients with SCD (n=118, 29.3%) had a ferritin level at baseline ≥1500 mg/dL, which is an accepted threshold above which to initiate chelation. Most people with an elevated ferritin had phenotypic SCA (homozygous Hb S) (n=111, or 94%). Over half of all SCD patients with a critically elevated ferritin were on CTT (n=64, 54%), and a similar number of people with SCD and critical ferritin levels were on chelation (n=64, 54%). Less than 1 in 4 had had a liver iron scan within 3 years (n=27, 23%). More than 1 in 3 patients with critical ferritin levels and no chelation therapy remained on CTT (n=21, not shown). Conclusions: Our multi-site registry, GRNDaD, prospectively surveyed a sizable population of adults with SCD, including data about iron overload. Of the adults in the GRNDaD registry with iron overload, we identified an unacceptably high fraction, nearly half, who were not on chelation. Most of these patients were people with phenotypic homozygous SCD. We are systematically addressing this deficiency with educational tools through GRNDaD. Since GRNDaD sites are academic centers across the country which focus on the management of SCD, we speculate that the problem of undertreated iron overload nationally is probably both widespread and under-recognized. We anticipate that, as GRNDaD continues to add additional sites, it will evolve as a robust resource through which to highlight important opportunities for clinical quality improvement in the expanding young adult population with SCD. GRNDaD may be a model for identifying and addressing deficiencies in current clinical practices for management of SCD. Disclosures Lanzkron: selexys: Research Funding; Ironwood: Research Funding; PCORI: Research Funding; HRSA: Research Funding; Pfizer: Research Funding; NHLBI: Research Funding; GBT: Research Funding; Prolong: Research Funding. Field:Incyte: Research Funding; Prolong: Research Funding; Ironwood: Consultancy, Research Funding. Desai:University of Pittsburgh: Research Funding; Selexy/Novartis: Research Funding; NIH: Research Funding; Ironwood: Other: Adjudication Committee; FDA: Research Funding; Pfizer: Research Funding. Little:PCORI: Research Funding; NHLBI: Research Funding; Hemex: Patents & Royalties: Patent, no honoraria; Doris Duke Charitable Foundations: Research Funding.

scholarly journals The relationships between pancreatic T2* values and pancreatic iron loading with cardiac dysfunctions,  hepatic and cardiac iron siderosis among Egyptian children and young adults with β-thalassaemia major and sickle cell disease: a cross-sectional study

F1000Research ◽  
2021 ◽  
Vol 9 ◽  
pp. 1108
Author(s):  
Khaled Salama ◽  
Amina Abdelsalam ◽  
Hadeel Seif Eldin ◽  
Eman Youness ◽  
Yasmeen Selim ◽  
...  
Keyword(s):  
Sickle Cell Disease ◽  
Pulmonary Artery ◽  
Iron Overload ◽  
Sickle Cell ◽  
Systolic Pulmonary Artery Pressure ◽  
Iron Loading ◽  
Thalassaemia Major ◽  
Cell Disease ◽  
Cardiac Iron ◽  
Diastolic Velocity

Background: Cardiac, hepatic and pancreatic T2* measured by magnetic resonance imaging (MRI) has been proven to be an accurate and non-invasive method for measuring iron overload in iron overload conditions. There is accumulating evidence that pancreatic iron can predict cardiac iron in young children because the pancreas loads earlier than the heart. The aim of our study was to assess the relationships between pancreatic T2* values and pancreatic iron loading with cardiac dysfunctions and liver and cardiac iron among patients with β-thalassaemia major (βTM) and sickle cell disease (SCD). Methods: 40 βTM and 20 transfusion-dependant SCD patients were included along with 60 healthy age and sex-matched controls. Echocardiography and Tissue Doppler Imaging were performed for all subjects as well as the control group.  Hepatic, cardiac and pancreatic iron overload in cases were assessed by MRI T2*. Results:  The mean age of our patients was 13.7 years with mean frequency of transfusion/year 12. Mean cardiac T2* was 32.9 ms and mean myocardial iron concentration was 0.7 mg/g; One patient had cardiac iron overload of moderate severity. Mean pancreatic T2* was 22.3 ms with 20 patients having mild pancreatic iron overload. Pancreatic T2* correlated positively peak late diastolic velocity at septal mitral annulus (r=0.269, p=0.038), peak early diastolic velocity at tricuspid annulus (r=0.430, p=0.001) and mitral annular plane systolic excursion (r=0.326, p=0.01); and negatively with end systolic pulmonary artery pressure (r=-0.343, p=0.007) and main pulmonary artery diameter (MPA) (r=-0.259, p=0.046). We couldn’t test the predictability of pancreatic T2* in relation to cardiac T2* as only one patient had cardiac T2*<20 ms. Conclusion: There was a relationship between pancreatic iron siderosis with cardiac dysfunction in multi-transfused patients with βTM and SCD. No direct relation between pancreatic iron and cardiac siderosis was detected.

Pancreatic Iron Deposition Following the Role of Iron Loading Among Transfusion Dependent Sickle Cell Disease Egyptian Children and Young Adults

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 4828-4828
Author(s):  
Mohsen Saleh Elalfy ◽  
Khalid Allam ◽  
Ahmed Ibrahim ◽  
Basant Mosaad ◽  
Fatma Soliman Elsayed Ebeid
Keyword(s):  
Young Adults ◽  
Sickle Cell Disease ◽  
Iron Overload ◽  
Sickle Cell ◽  
Serum Ferritin ◽  
Iron Loading ◽  
Cell Disease ◽  
Liver Iron ◽  
Cardiac Iron ◽  
Iron Load

Background: Transfusion in sickle cell disease (SCD) is uncommon but a well-defined practice; either as a replacement in severe anemia or as a prophylactic therapy for its major complications mainly stroke. Differential iron loading in SCD especially the extrahepatic organs is not fully studied. Primary objective is to measure pancreatic iron load among Egyptian transfusion-dependant SCD patients by using MRI T2* relaxometry method. Secondaryobjective is to correlate pancreatic iron load to transfusion iron input, both hepatic and cardiac iron load, trend of serum ferritin. Subjects and Methods: Sixty-six transfusion-dependant SCD child and young adults 8-25 years with more than twenty transfusions before enrollment, non was on regular exchange transfusion; they underwent clinical and laboratory assessments; complete hemogram, serum ferritin and serum amylase. All patients performed MRI examination on a 1.5- Tesla super conductive MR Philips scanner in MRI unit in Ain Shams University Hospital; the study takes about 10 -15 minutes. Radiological quantification of iron overload was performed via simple mathematical models using Microsoft Excel Spread Sheet for heart, pancreas, and kidneys. Results: The mean age of the studied SCD patients were 15.68 ± 7.02 years, they were 35 male (53.0%), 43 of them (65.2%) had positive family history of SCD. All were multiple transfusion; 22 for cardiopulmonary complication and acute chest syndrome (ASC), nine for stroke prevention and 35 for frequent sickling crisis and symptomatic anemia. Most of patients (80.3%) were on chelation therapies that were mainly (92.5%) oral mono-therapy. High frequencies of comorbidities were recorded in the studied cohort; delayed puberty (65.2%), hepatitis C infection (23.1%) and stroke (14.1%). The studied SCD patients had median transfusion index of 120ml/kg/year with mean iron overload per day 0.23 ± 0.15 mg/kg and half of them had serum ferritin > 2500ug/L. Almost two-thirds had moderate to severe liver iron overload with median LIC 11.63 mg/g liver dry weight, none had cardiac iron overload with median cardiac T2* 31 msec and nearly half of them (42.2%) showed marked decrease in signal intensity of renal cortex with relative sparing of the renal medulla and pelvis. Most of them (86%) had normal to mild pancreatic iron overload with median pancreatic R2* 53.8 msec. Pancreatic R2 level was not significantly correlated to either transfused iron, liver iron or serum ferritin and amylase. Patients with moderate to severe pancreatic iron overload had lower pre-transfusion hemoglobin level (p=0.004), higher level of marker of hemolysis (total bilirubin (p=0.012) and indirect bilirubin (p=0.048) than those with normal pancreatic MRI. Radiological quantification of iron overload was performed via a simple cheap and quick method for analysis of data. Conclusion: Moderately heavy transfused patients with SCD had no iron overload in the heart; pancreas follow same pattern as heart with minimal or no pancreatic iron loading, however moderate to severe hepatic iron loading. Whether iron loading might be related only to frequency of transfusion or also to frequency of vaso-occlusive will be discussed. Disclosures No relevant conflicts of interest to declare.

scholarly journals Patterns of hepatic iron distribution in patients with chronically transfused thalassemia and sickle cell disease

2009 ◽  
Vol 84 (8) ◽  
pp. 480-483 ◽  
Author(s):  
Nilesh R. Ghugre ◽  
Ignacio Gonzalez-Gomez ◽  
Ellen Butensky ◽  
Leila Noetzli ◽  
Roland Fischer ◽  
...  
Keyword(s):  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Hepatic Iron ◽  
Cell Disease ◽  
Iron Distribution

Non Transferrin Bound Labile Plasma Iron and Iron Overload in Sickle Cell Disease: a Comparative Study Between Sickle Cell Disease and β Thalassemic Patients.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 4625-4625
Author(s):  
Ariel Koren ◽  
Daniel Fink ◽  
Osnat Admoni ◽  
Yardena Tennenbaum-Rakover ◽  
Carina Levin
Keyword(s):  
Sickle Cell Disease ◽  
Iron Overload ◽  
Sickle Cell ◽  
Research Funding ◽  
Iron Status ◽  
Blood Transfusions ◽  
Grey Zone ◽  
Cell Disease ◽  
Plasma Iron ◽  
Oncology Research

Abstract Abstract 4625 BACKGROUND Blood transfusions are the standard of care in β thalassemia and transfusions are also indicated in Sickle Cell Disease (SCD) patients with hypersplenism, recurrent vaso-occlusive crises and for stroke prevention. Iron overload caused by blood transfusions in thalassemia and in SCD may affect morbidity and mortality. Recent studies of iron overload in SCD suggest that the biologic features of SCD and the chronic inflammatory state may protect SCD patients from iron damage. DESIGNS AND METHODS In view of the controversy regarding the effect of iron overload in patients with SCD we studied the iron status, including non transferrin bound iron (NTBI) and labile plasma iron (LPI) levels in a cohort of thirty six SCD patients and compare the results with 43 thalassemia patients. RESULTS Our results indicate that none of the SCD patients had clinical symptoms of iron overload. Only two SCD patients had NTBI values in the grey zone (0.4 units) and none had positive values. By contrast, 14 patients with Thalassemia Major and 3 with Thalassemia Intermedia had NTBI values above 0.6, level that are in the positive pathological range. Similarly, four thalassemia patients, but only one SCD patient had positive LPI levels. CONCLUSIONS The parameters of iron status in SCD patients, even after frequent transfusions are different when compared to patients with thalassemia. The low NTBI and LPI levels found in patients with SCD are in keeping with the absence of clinical signs of iron overload in this disease. Disclosures: Koren: Novartis Oncology: Research Funding. Levin:Novartis Oncology: Research Funding.

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