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

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.

Download Full-text

Consequences and management of iron overload in sickle cell disease

Hematology ◽

10.1182/asheducation-2013.1.447 ◽

2013 ◽

Vol 2013 (1) ◽

pp. 447-456 ◽

Cited By ~ 57

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.

Download Full-text

Plasma level of matrix metalloproteinase-9 in patients with sickle cell disease and its correlation to myocardial iron overload

10.21203/rs.3.rs-109357/v1 ◽

2020 ◽

Author(s):

Tamer Hassan ◽

Mohamed Badr ◽

Mohamed Arafa ◽

Doaa Abdel Rahman ◽

Manar Fathy ◽

...

Keyword(s):

Sickle Cell Disease ◽

Iron Overload ◽

Sickle Cell ◽

Serum Ferritin ◽

Plasma Levels ◽

Restrictive Cardiomyopathy ◽

Myocardial Iron ◽

Cell Disease ◽

Cardiac Iron ◽

Cardiac Iron Overload

Abstract Cardiac iron overload is secondary to chronic blood transfusion in patients with sickle cell disease (SCD). Iron overload cardiomyopathy is a restrictive cardiomyopathy associated with systolic and diastolic dysfunction. Matrix metalloproteinases (MMPs) are a family of zinc-dependent endopeptidases responsible for tissue remodeling. Many studies offer strong evidence for the role of MMP-9 in LV remodeling. We aimed to detect plasma levels of MMP-9 in patients with SCD and its correlation to myocardial iron overload. A case control study was carried out on 50 patients with SCD and 50 age and sex matched healthy controls. Assessment of cardiac iron overload in patients by MRI T2* was performed. Plasma MMP-9 levels were measured for patients and controls using ELISA. SCD patients had significantly higher levels of MMP-9 than controls. There was highly significant correlation between plasma levels of MMP-9 and serum ferritin. Patients with vaso-occlusive crises (VOC) > 5/year had significantly higher levels of MMP-9 than those with VOC ≤ 5 /year. No significant correlation was found between MMP-9 and cardiac T2*. MMP-9 seems to be a useful marker in SCD patients. Patients with serum ferritin > 1000 ng/ml, recurrent VOC > 5 /year had significantly higher MMP-9 serum levels than others.

Download Full-text

Serum Ferritin a Predictor of Iron Overload in Patients with Thalassemia and Sickle Cell Disease?.

Blood ◽

10.1182/blood.v104.11.3789.3789 ◽

2004 ◽

Vol 104 (11) ◽

pp. 3789-3789 ◽

Cited By ~ 1

Author(s):

Zahra Pakbaz ◽

Roland Fischer ◽

Richard Gamino ◽

Ellen B. Fung ◽

Paul Harmatz ◽

...

Keyword(s):

Sickle Cell Disease ◽

Iron Overload ◽

Sickle Cell ◽

Serum Ferritin ◽

Iron Concentration ◽

Cell Disease ◽

Liver Iron Concentration ◽

Liver Iron ◽

Iron Stores ◽

Significant Difference

Abstract Introduction: Monitoring iron overload by serum ferritin in patients with hemosiderosis is still a routine practice although its limitations are widely studied and well known. Using non-invasive liver iron assessment by quantitative MRI or by biomagnetic liver susceptometry (BLS) with SQUID biomagnetometers would be the better alternative, however, these methods are available at only a few centers worldwide. Objective: To determine the relationship between serum ferritin (SF) and liver iron concentration (LIC), measured by BLS at CHRCO, in patients with different types of hemosiderosis. Methods and Patients: A total of 97 patients with thalassemia (TM: 3 to 52 y, 54% females) and 39 patients with sickle cell disease (SCD: 5 to 49 y, 60% female) were prospectively assessed for LIC and SF. Both tests were performed within 2 weeks of each other. Most patients with TM and SCD were chronically transfused, while 10 b-thalassemia intermedia (TI), 5 HbE/β-thalassemia (HbE), and 5 SCD patients were not on transfusion programs. LIC was measured by LTc SQUID biosusceptometer system (Ferritometer®, Model 5700, Tristan Technologies, San Diego, USA) under the standardized Hamburg-Torino-Oakland protocol. A non-parametric test (U-test) was utilized to analyze differences between SF and LIC data. Results: In chronically transfused TM and SCD patients, the median SF and LIC were very similar (Table I). In TI&HbE patients, ferritin results were disproportionately low with respect to LIC. In order to improve prediction of iron stores by SF, the SF/LIC ratio was calculated. There was a significant difference between the median ratios of the two groups of transfused and non- transfused thalassemia patients, 0.82 vs. 0.32 [μg/l]/[μg/gliver], respectively (p < 0.01). In SCD patients the ratio is significantly (p < 0.01) higher. Conclusion: Present data confirm ferritin to be a poor predictor of liver iron stores both in sickle cell disease and thalassemia. Relying only on ferritin to monitor iron overload in patients with hemosiderosis can be misleading, especially, in sickle cell disease and non-transfused thalassemia patients. Taking into account disease specific ferritin-LIC relations, could improve the prediction of iron stores. However, assessment of liver iron stores is the ultimate method to initiate and adjust chelation treatment in order to avoid progressive organ injury. Table I. Median values and ranges ( − ) of serum ferritin (SF) and liver iron concentration (LIC) in transfused (Tx) and non-transfused (non-Tx) hemosiderosis patients. Patient group n SF μg/l] LIC [mg/gliver ] SF:LIC Thalassemia Tx 82 1721 (209–8867) 3424 (364–7570) 0.82 (0.3–1.8) TI &HbE non-Tx 15 766 (52–2681) 2174 (226–5498) 0.32 (0.1–1.4) SCD Tx 34 2757 (400–9138) 1941 (518–6670) 1.2 (0.6–3.3)

Download Full-text

Serum Ferritin in Children with Sickle Cell Disease on Chronic Transfusion: Measure of Iron Overload or End Organ Injury? STOP/STOP II Liver Iron Ancillary Study.

Blood ◽

10.1182/blood.v108.11.791.791 ◽

2006 ◽

Vol 108 (11) ◽

pp. 791-791 ◽

Cited By ~ 4

Author(s):

Tom Adamkiewicz ◽

Miguel R. Abboud ◽

Julio C. Barredo ◽

Melanie Kirby-Allen ◽

Ofelia A. Alvarez ◽

...

Keyword(s):

Sickle Cell Disease ◽

Iron Overload ◽

Sickle Cell ◽

Serum Ferritin ◽

Iron Removal ◽

Organ Injury ◽

Cell Disease ◽

Liver Iron ◽

Flow Measurements ◽

Transfusion Therapy

Abstract Between 1995 and 2004, two NIH-sponsored studies (STOP/STOP II) showed that children with sickle cell disease (SCD) and abnormal transcranial Doppler blood flow measurements (high stroke risk) are protected from stroke with regular blood transfusions. Iron overload, which may lead to complications and requires iron removal therapy, was monitored by serum ferritin (SF). Liver iron concentration (LIC) measurement was not mandated by protocol and was performed at investigator discretion. Biopsy dates and lab values were captured during STOP/STOP II, providing an opportunity to validate SF against LIC. 75 LICs on 36 patients (19 female, 17 male) at 8 centers were obtained. No liver biopsy complications were reported. LICs were correlated with STOP/STOP II core laboratory SF and alanine aminotransferase (ALT) obtained within 180 days of LICs. Median age at first biopsy was 11.1 years (range, 4.5–17.8), median time from start of transfusion was 36 months (range, 2–100). Iron removal treatment was initiated a median 23 months (range, 4–108) from start of transfusion, with deferoxamine (n=27), and/or exchange transfusion (n=9). 21 pts (58%) had multiple LIC measures: 2 (n=9), 3 (n=8), 4 (n=2), 5 (n=2). Last LICs on iron removal therapy were obtained a median 72 months (range, 35–124) from start of transfusion. Correlation between SFs and LICs were r=-0.06 (n=18) for first LICs obtained prior to iron removal therapy, r=0.50 (n=17) for last LICs obtained on iron removal therapy, and r=0.51 for all LICs (n=60). Pts with single/last LIC >=15 mg/gram dry liver were significantly more likely to have ALTs >=45 IU/L compared to those with LICs <15 mg/gram (5/12 vs. 1/18; odds ratio 12.1; 95% CI 1.2–123.6; p=0.03). Pts with LIC >=15 mg/gram and ALT >=45 IU/L tended to have higher SFs then those with normal ALT (mean SF 4927 ng/ml, 95% CI 1739–8115 vs. mean SF 2255 ng/ml, 95% CI 1599–2912). 37% (7/19) of pts with LIC >=15 mg/gram had SFs <2000 ng/ml. 55% (11/20) of pts with repeated LICs, had last LICs <15 mg/gram after initiation of iron removal therapy. SF did not correlate with LICs after initiation of blood transfusion therapy and correlated weakly after initiation of iron removal therapy. Over 1/3 of children with evidence of significant iron overload, as measured by LICs, had low serum SFs (<2000 ng/ml), leading to a potentially erroneous interpretation of low iron stores. A significant portion of pts with elevated LICs had evidence of liver injury (ALT elevation). SF elevation observed in some pts may be due in part to end organ injury. Sustained iron overload control was achieved in over 1/2 of pts examined with repeated LICs.

Download Full-text

Serum Ferritin Predicts Liver but Not Cardiac Iron Burden by Noninvasive MRI in Sickle Cell Disease (SCD.

Blood ◽

10.1182/blood.v112.11.1421.1421 ◽

2008 ◽

Vol 112 (11) ◽

pp. 1421-1421 ◽

Cited By ~ 1

Author(s):

Robert I. Liem ◽

Cynthia Rigsby ◽

Richard J. Labotka ◽

Andrew DeFreitas ◽

Alexis A. Thompson

Keyword(s):

Iron Overload ◽

Serum Ferritin ◽

Iron Content ◽

Iron Loading ◽

Cell Disease ◽

Liver Iron ◽

Cardiac Iron ◽

Liver Iron Content ◽

The Mean

Abstract BACKGROUND: Assumptions about iron loading as well as the utility of ferritin to predict transfusional iron overload among individuals with sickle cell disease (SCD) are largely based on extrapolation from data generated in patients with thalassemia major (TM). Yet recent studies suggest the natural history of iron overload in patients with SCD differs significantly from chronically transfused patients with TM. We sought to evaluate the extent of myocardial and hepatic siderosis using noninvasive imaging in chronically transfused patients with SCD and examine its clinical associations, including relationship to long-term trends in serum ferritin, transfusion history, chelation status and markers of hemolysis and inflammation. METHODS: We evaluated 17 subjects (mean age 15±3.6 yrs, range 9 to 20). The mean transfusion duration was 7.3±3.6 yrs (range 2 to 15). Thirteen (76%) patients were on chelation with deferasirox at the time of screening; 4 were not on chelation Rx. MRI T2*/R2* of the heart and liver using a multiple gradient echo sequence was performed on a single 1.5T GE scanner. Hepatic iron concentration (HIC) values were predicted from liver R2* values. RESULTS: Mean HIC in subjects was 9.9±6.7 mg/gm liver dry weight (range 2.5 to 20.8) and was ≥15 mg/gm in 6/17 (35%) subjects. The mean long-term serum ferritin (past 5 yrs, or duration of transfusion if < 5yrs) was 2318±1122 ng/mL (range 541 to 4225). Using Pearson’s correlation coefficient, we observed a significant relationship between HIC and ferritin (r=0.765, p=<0.001). We generated a receiver operator characteristic (ROC) curve to assess the utility of ferritin as a predictor of elevated HIC, using a threshold HIC thought to predict serious iron-related complications. A ferritin cut-off value ≥2164 ng/mL correctly identified 80% of cases of HIC ≥15 mg/gm (AUC 0.96, p=0.003) in our subjects with 83% sensitivity and 73% specificity. Despite markedly elevated HIC and ferritin values in some subjects, none had myocardial siderosis. All 17 subjects had cardiac MRI T2* values in the normal range > 25 ms. Cardiac iron load measured by T2* did not correlate with HIC or serum ferritin. We examined C-reactive protein (CRP) and B-type natriuretic peptide (BNP) as markers for inflammation and myocardial strain, respectively, in our subjects but neither demonstrated a significant relationship to ferritin or MRI findings. BNP, however, did correlate modestly with both age (r=−0.574, p=0.013) and left ventricular ejection fraction on cardiac MRI (r=0.510, p=0.036). A subset of subjects (n=8) had histologic iron measurements by percutaneous liver biopsy (LBx) within 6 months of MRI. While liver iron content by LBx correlated significantly with HIC by MRI (r=0.759, p=0.03), liver iron content by LBx did not correlate with ferritin (r=0.312, p=0.452). CONCLUSION: We found that serum ferritin is a good predictor of liver iron by MRI R2*, and that long term ferritin values ≥2164 ng/mL predict significant hepatic iron overload as assessed by this noninvasive method. We did not observe appreciable cardiac iron loading in our subjects with SCD, which otherwise might have been predicted by elevated HIC alone, as in individuals with TM. These data suggest that reliable, long term surveillance of transfusion-induced iron overload in SCD may be achieved using serum ferritin and HIC by MRI R2* as surrogate markers of hepatic siderosis rather than relying on liver iron content measured invasively by LBx. Also, previously determined thresholds for significant cardiac iron loading in TM, based on degree of hepatic siderosis, may not be applicable in SCD. Further investigation into alternative mechanisms of iron loading or distribution in these related but distinct disorders is warranted.

Download Full-text

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

Blood ◽

10.1182/blood-2018-99-114123 ◽

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.

Download Full-text

Serum ferritin level changes in children with sickle cell disease on chronic blood transfusion are nonlinear and are associated with iron load and liver injury

Blood ◽

10.1182/blood-2009-02-203323 ◽

2009 ◽

Vol 114 (21) ◽

pp. 4632-4638 ◽

Cited By ~ 56

Author(s):

Thomas V. Adamkiewicz ◽

Miguel R. Abboud ◽

Carole Paley ◽

Nancy Olivieri ◽

Melanie Kirby-Allen ◽

...

Keyword(s):

Sickle Cell Disease ◽

Liver Injury ◽

Blood Transfusion ◽

Iron Overload ◽

Sickle Cell ◽

Serum Ferritin ◽

Ferritin Level ◽

Liver Weight ◽

Cell Disease ◽

Iron Load

AbstractChronic blood transfusion is increasingly indicated in patients with sickle cell disease. Measuring resulting iron overload remains a challenge. Children without viral hepatitis enrolled in 2 trials for stroke prevention were examined for iron overload (STOP and STOP2; n = 271). Most received desferrioxamine chelation. Serum ferritin (SF) changes appeared nonlinear compared with prechelation estimated transfusion iron load (TIL) or with liver iron concentrations (LICs). Averaged correlation coefficient between SF and TIL (patients/observations, 26 of 164) was r = 0.70; between SF and LIC (patients/observations, 33 of 47) was r = 0.55. In mixed models, SF was associated with LIC (P = .006), alanine transaminase (P = .025), and weight (P = .026). Most patients with SF between 750 and 1500 ng/mL had a TIL between 25 and 100 mg/kg (72.8% ± 5.9%; patients/observations, 24 of 50) or an LIC between 2.5 and 10 mg/g dry liver weight (75% ± 0%; patients/observations, 8 of 9). Most patients with SF of 3000 ng/mL or greater had a TIL of 100 mg/kg or greater (95.3% ± 6.7%; patients/observations, 7 of 16) or an LIC of 10 mg/g dry liver weight or greater (87.7% ± 4.3%; patients/observations, 11 of 18). Although SF changes are nonlinear, levels less than 1500 ng/mL indicated mostly acceptable iron overload; levels of 3000 ng/mL or greater were specific for significant iron overload and were associated with liver injury. However, to determine accurately iron overload in patients with intermediately elevated SF levels, other methods are required. These trials are registered at www.clinicaltrials.gov as #NCT00000592 and #NCT00006182.

Download Full-text

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 ◽

10.12688/f1000research.25943.2 ◽

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.

Download Full-text

Serum ferritin and total units transfused for assessing iron overload in adults with sickle cell disease

British Journal of Haematology ◽

10.1111/j.1365-2141.2012.09060.x ◽

2012 ◽

Vol 157 (5) ◽

pp. 645-647 ◽

Cited By ~ 15

Author(s):

Emma Drasar ◽

Nisha Vasavda ◽

Norris Igbineweka ◽

Moji Awogbade ◽

Marlene Allman ◽

...

Keyword(s):

Sickle Cell Disease ◽

Iron Overload ◽

Sickle Cell ◽

Serum Ferritin ◽

Cell Disease

Download Full-text

Erythrocytapheresis therapy to reduce iron overload in chronically transfused patients with sickle cell disease

Blood ◽

10.1182/blood.v83.4.1136.1136 ◽

1994 ◽

Vol 83 (4) ◽

pp. 1136-1142 ◽

Cited By ~ 95

Author(s):

HC Kim ◽

NP Dugan ◽

JH Silber ◽

MB Martin ◽

E Schwartz ◽

...

Keyword(s):

Sickle Cell Disease ◽

Iron Overload ◽

Sickle Cell ◽

Chelation Therapy ◽

Iron Chelation ◽

Cell Disease ◽

Donor Blood ◽

Iron Load ◽

Blood Usage ◽

Hb S

Abstract Chelation therapy with deferoxamine is effective in preventing the risk of transfusional iron overload, but treatment failure is common because of noncompliance. To reduce the transfusional iron load, we have evaluated longterm erythrocytapheresis in 14 subjects with sickle cell disease and stroke (11) or other complications (3) as an alternative to simple transfusion. Subjects were treated with erythrocytapheresis using the Haemonetics V50 (Haemonetics Corp, Braintree, MA) to maintain the target pretransfusion hemoglobin S (Hb S) level less than 50% for 6 to 71 months. The transfusional iron load and the donor blood usage were analyzed for a 6- to 36-month study period and were compared with similar data from a subset of 7 subjects previously treated with conventional (target Hb S < 30%) and modified (target Hb S < 50%) simple transfusion protocols. The effect of erythrocytapheresis on iron accumulation was determined by assessment of serum ferritin levels in the absence of iron chelation. The mean transfusional iron load and donor blood usage with erythrocytapheresis were 19 +/- 14 mg iron/kg/yr (range, 6 to 50) and 188.4 +/- 55.2 mL packed-red blood cells (RBC)/kg/yr (range, 107 to 281), respectively. Of 6 subjects receiving no iron chelation therapy, 5 maintained normal or nearly normal serum ferritin levels during 11 to 36 months of erythrocytapheresis. In comparison with conventional simple transfusion and modified simple transfusion, erythrocytapheresis reduced iron loading by 87% (P < .01) and 82% (P < .01), respectively, but increased donor blood usage by 23% and 73%, respectively. Subjects with pre-erythrocytapheresis Hb levels > or = 8.0 g/dL had lower iron accumulation (P < .001) and less donor blood usage (P < .005) than subjects with Hb levels < or = 8.0 g/dL. Although donor blood usage is increased in comparison with simple transfusion, long-term erythrocytapheresis markedly reduces or prevents iron accumulation. This form of transfusion therapy allows the cessation of iron chelation in well-chelated subjects and, if used as the initial form of transfusion therapy, may prevent long-term complications of sickle cell disease without risk of iron overload and the need for chelation therapy.

Download Full-text