Liver Transient Elastography (FibroScan) Correlates with Liver Iron Concentration and Reflects Liver Fibrosis In Patients with Sickle Cell Disease

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 1646-1646 ◽  
Author(s):  
Ersi Voskaridou ◽  
Maria Schina ◽  
Eleni Plata ◽  
Dimitrios Christoulas ◽  
Maria Tsalkani ◽  
...  
Keyword(s):  
Liver Fibrosis ◽  
Iron Overload ◽  
Hepatic Fibrosis ◽  
Sickle Cell ◽  
Serum Ferritin ◽  
Transient Elastography ◽  
Iron Concentration ◽  
Liver Stiffness ◽  
Cell Disease ◽  
Liver Iron

Abstract Abstract 1646 Liver transient elastography (FibroScan) is an interesting new technology that allows estimation of hepatic fibrosis through measurement of liver stiffness. The technique is based on changes in tissue elasticity induced by hepatic fibrosis and is considered as a noninvasive, reproducible and reliable method to assess hepatic fibrosis as well as to diagnose liver cirrhosis. Hepatic iron overload is a severe complication of chronic transfusion therapy in patients with hemoglobinopathies and plays an important role in the development of hepatic fibrosis and cirrhosis. Iron overload is present in several cases of sickle cell disease (SCD) including sickle cell anemia (HbS/HbS) and double heterozygous sickle-cell/beta-thalassemia (HbS/beta-thal). The aim of the study was to evaluate liver fibrosis by measuring the liver rigidity (Liver Stiffness Measurement, LSM, kPascals) using transient elastography (FibroScan, Echosens, Paris, France) in patients with SCD and explore possible correlations with clinical and laboratory characteristics of the patients, including iron overload. We studied 110 consecutive patients with SCD who are followed-up in the Thalassemia Center of Laikon General Hospital in Athens, Greece. Forty-four patients were males and 66 females; their median age was 44 years (range: 21–73 years). Twenty-two patients had HbS/HbS and 88 patients had HbS/beta-thal. On the day of Fibroscan, all patients had a thorough hematology and biochemical evaluation, including hemoglobin, reticulocyte counts, serum ferritin, liver biochemistry, bilirubin, lactate dehydrogenase (LDH) and serology for viral hepatitis. Liver iron concentration was evaluated by magnetic resonance imaging (MRI) T2* in all patients. The median LSM of all patients was 6.1 kPascals (range: 3.4–48.8 kPascals) with no differences between HbS/HbS (6.1 kPascals, 3.5–17.3 kPascals) and HbS/beta-thal (6.1 kPascals, 3.4–48.8 kPascals) patients (p=0.835). LSM values strongly correlated with liver MRI T2* values (r=0.337, p<0.001), serum ferritin (r=0.328, p=0.001), number of transfusions (r=0.332, p=0.001), bilirubin (r=0.299, p=0.003), LDH (r=0.287, p=0.004), Hb (r=-0.275, p=0.006) and reticulocyte counts (r=0.244, p=0.015). LSM values showed also strong positive correlations with biochemical indicators of liver function: gamma-glutamyl transpeptidase (r=0.522, p<0.0001), glutamic oxaloacetic transaminase (r=0.484, p<0.0001), glutamic pyruvic transaminase (r=0.422, p<0.0001), alkaline phosphatase (r=0.334, p=0.001), gamma-globulin (r=0.296, p=0.005) and weak correlation with PT-International Normalized Ratio (r=0.184, p=0.094). The above correlations were similar in patients with HbS/HbS and in patients with HbS/beta-thal. However, in HbS/HbS patients the correlation between LSM and liver T2* values was very strong (r=0.770, p=0.001). Patients who were regularly transfused had higher values of LSM (median: 6.7 kPascals, range: 2.3–48.8 kPascals) compared with patients who were sporadically transfused or were not transfused (4.4 kPascals, 3.6–17.5 kPascals, p=0.003). Patients who were under iron chelation therapy had lower values of LSM (6.3 kPascals, 3.4–15 kPascals) compared with those who did not receive iron chelators (13.9 kPascals, 8.5–17.3 kPascals, p=0.013). We found no correlations between the presence of HBV or HCV positivity and the levels of LSM. In conclusion, FibroScan may constitute a reliable and easy to apply noninvasive method to assess liver fibrosis in patients with SCD; the strong correlations between LSM values with MRI T2* values and serum ferritin supports this observation. Furthermore, FibroScan seems also to reflect the presence of chronic hepatic injury in these patients. If our results are confirmed by other studies, FibroScan may be regularly used in the management of SCD patients in whom liver is the main target organ of the disease. Disclosures: No relevant conflicts of interest to declare.

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

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 3789-3789 ◽  
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)

Transient Elastography May Predict Liver Iron Overload in Adult Thalassaemia Patients

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 5407-5407 ◽  
Author(s):  
Vasilios Perifanis ◽  
Efthimia Vlachaki ◽  
Emmanouil Sinakos ◽  
Ioanna Tsatra ◽  
Maria Raptopoulou-Gigi ◽  
...  
Keyword(s):  
Liver Fibrosis ◽  
Iron Overload ◽  
Hepatic Fibrosis ◽  
Transient Elastography ◽  
Iron Concentration ◽  
Thalassaemia Major ◽  
Liver Iron Concentration ◽  
Liver Iron ◽  
Liver Iron Overload ◽  
T2 Mri

Abstract Although it is life saving, transfusion therapy has resulted in the majority of thalassemia patients being at risk for hemosiderosis-induced organ damage. Liver Iron Concentration (LIC) assessed by liver biopsy is considered the most accurate and sensitive method for determining body iron burden in patients with iron overload. The development of liver fibrosis is more closely related to liver iron concentration. Transient elastography (FibroScan, FS), which measures liver stiffness (LS), is a novel, noninvasive method to assess liver fibrosis. Whether FS is useful in the detection of preexisting liver iron overload in patients presenting with thalassaemia major without chronic viral hepatitis, is unclear. On the other hand, Magnetic Resonance Imaging (MRI) is a relatively inexpensive, widely available but more time consuming method that has long been considered as a useful tool for the non-invasive estimation of tissue iron content in multiple transfused patients with thalassemia. Aim: To study the prevalence and severity of liver fibrosis of transfusion dependent thalassaemia major patients, and correlate the MRI.LIC with the measurements of FS. Methods-Patients: The applicability for FS (Echosens, Paris, France) was defined as at least 10 valid measures and a success rate (number of valid measures/total number of LS Measures, LSM) ≥60% and a ratio of interquartile range/stiffness ≤0,2. Most subjects with FS scores below 5.1 kilopascals (kPa) are considered to have minimal fibrosis (grade F0 or F1, METAVIR score) according to the literature. The cut off FS values for diagnosing different stages of hepatic fibrosis were defined as &gt; 7.9kPa for F≥2, &gt; 10.3kPa for F≥3 and &gt; 11.9kPa for F=4. A total of 43 thalassaemic patients 23 males/20 females, median age 26,8±4,9 years, regularly transfused (pre-transfusion haemoglobin 9,7g/dl) were included in the study. All patients were hepatitis C virus (HCV) negative and chelated with different drugs (13 on deferasirox, 12 on deferiprone, 5 on desferrioxamine and 13 on combined therapy). Median ferritin levels were 1552±1576ng/ml. Liver tests (AST, ALT, γGT and Alkaline Phosphatase) were done simultaneously to all patients. Twenty-two of the 43 patients underwent liver iron determination (LIC) simultaneously by two methods: T2* Magnetic Imaging (T2*MRI) assessment and by calculation of MR-Hepatic Iron Concentration (MR.HIC) values (based on an algorithm developed by Gandon et al (Lancet 2004), using liver to muscle ratios in five axial gradient-echo sequences). T-test was used in statistical analysis to compare means. Results: Applicability of LSM was 100%. Overall median LSM was 8,25±6,05kPa (range 4–40,3kPa). Nineteen (44,1%) patients had FS&lt;6,1kPa (notably 8/19 patients below 5,1kPa), 13 (30,2%) had &lt;7,9kPa, 4 (9,3%) had &lt;10,3kPa, 2 (4,7%) had &lt;11,9kPa and 5 (11,7%) above 11,9kPa. Total FS correlated with Ferritin (r=0,39, p=0,008). Using the cutt-off value of 6,1 kPa for FS measurements, patients were divided in two groups with different ferritin levels: A (&lt;6,1kPa) 1039±758ng/ml vs B (&gt;6,1kPa) 1833±1742ng/ml, p&lt;0,03. FS values of the three different major therapy groups did not differ significantly. FS (22pts) correlated negatively with T2*MRI results (r=−0,39, p=0,07) and positively with MR.HIC results (r=0,49, p=0,02). There was no correlation with liver function tests. Conclusions: Severe haemosiderosis and hepatic fibrosis are common in patients with thalassaemia major despite the use of chelation therapy and the absence of HCV. Elastography has several characteristics that make it a desirable method for assessing hepatic fibrosis. In addition to being noninvasive and painless, it is also quick, inexpensive, and produces consistent results. It can also be useful as an alternative to check for liver iron overload, as abnormal results predict heavy liver iron overload. Further longitudinal and prospective studies are necessary to confirm these preliminary data.

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.

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 &gt; 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 &gt;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 Non Invasive Evaluation of Hepatic Iron Concentration By Fibroscan in Transfusion-Dependent Egyptian Patients with Chronic Hemolytic Anemia

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 1061-1061
Author(s):  
Amal El-Beshlawy ◽  
Dalia Omran ◽  
Hala Mohsen Abdullatif ◽  
Niveen Salama ◽  
Mohamed Ahmed Abdel Naeem ◽  
...  
Keyword(s):  
Liver Fibrosis ◽  
Iron Overload ◽  
Sensitivity And Specificity ◽  
Transient Elastography ◽  
Iron Concentration ◽  
Hepatic Iron ◽  
Cell Disease ◽  
Non Invasive ◽  
Cutoff Values ◽  
Chronic Hemolytic Anemia

Abstract Background: Transient elastography (Fibroscan®) is an ultrasound technique used to measure liver stiffness (LS), and thus assess for liver fibrosis, in patients with various chronic hepatic disorders. It can also be used to predict severity in multiple other diseases that might affect LS such as amyloidosis and possibly conditions associated with iron overload. Objectives: To assess the frequency of liver fibrosis in patients with chronic hemolytic anemia using Transient elastography (Fibroscan®), and to determine the reliability of this tool as a non-invasive method to predict hepatic iron content as compared to liver iron concentration (LIC) measured by magnetic resonance imaging (MRI). Patients and methods: Seventy-five transfusion dependent patients (50 β-thalassemia major;25 sickle cell disease) with a mean age of 13.4±5.2 years in addition to 75 -age and sex matched- healthy children were recruited. All subjects underwent assessment of LS in kilopascals (kPa), by Transient elastography measurement using FibroScan (Echosens, Paris, France І). Steady state serum ferritin (SF), and hepatitis B serologies (HBsAg and antiHB core antibodies) were assessed by enzyme linked immunoassay (ELISA). LIC values, within 6 months' duration, as identified by quantitative MRI of hepatic iron stores as a signal intensity ratio method based on T1 and T2* contrast imaging without gadolinium were retrieved. Informed consent was obtained from patients' legal guardians prior to enrollment in the study. Results: The median SF was 2280 ng/ml (84% had values exceeding 1000 ng/ml). The median LIC was 13.86 mg/g dw (78.7% patients showed LIC above 7 mg/g dw). The median cardiac T2* was 30.8 ms (3 patients had values below 20). Fifty-two (69.3%) patients were categorized as F0-1 and 21 (28%) were stage F2, 2 (1.3%) were stage F3, and 2 patients had severe fibrosis. The mean and median fibroscan (FS) values were 6.19 ±1.76 kPa and 5.9 kPa (range 3 to 14.1) respectively. Patients had significantly higher mean FS compared to control group (p ˂0.001). Patients with no or mild fibrosis (F0-1) had lower FS values (5.3kPa) compared to patients with fibrosis grades 2-4 (p ˂0.001). FS values were not affected by disease type (thalassemia or sickle cell disease), age (above 12 years), or HCV sero-positivity. FS values correlated with SF (r=0.410, p˂ 0.001). Simple regression analysis of the two variables suggested that changes in SF were associated with minimal but significant changes in FS values (p=0.04) with good agreement (kappa =0.324, p=0.003). LIC did not differ in relation to grade of fibrosis (p>0.05), did not correlate with FS values (r= 0.014, p=0.908), and no changes in FS were expected with LIC changes on regression analysis (p=0.466) with low agreement between LIC and FS at cutoff value 5.3 kPa (kappa = 0.015, p=0.9). Sensitivity and specificity of FS values to predict LIC were high at cutoff values ranging between 3.2 to 3.75 kPa but decreased markedly at higher cutoff values. On comparing sensitivity and specificity of FS values in prediction of iron overload at different cutoff values by ROC curve, it could not significantly predict iron overload (p=0.7). No correlations were found between LIC and other variables including SF (r=0.2), and changes in SF were not significantly associated with changes in LIC values (p =0.089). However, sensitivity and specificity of SF in predicting LIC were good at cutoff 1003.85 ng/ml but decreased markedly at higher cutoff values. Comparing its sensitivity and specificity to that of SF in the prediction of iron overload at different cutoff values by ROC curve, FS could not predict iron overload accurately (p=0.9) and the degree of agreement between these two variables as indicators of iron overload was low (kappa=0.063, p=0.478). Conclusion: Fibroscan could be a valuable tool to assess the degree of liver fibrosis in patients with elevated SF, but it does not appear to reliably predict LIC in such group of patients especially with severe iron overload. FS values were not affected by disease type, age above 12 years, or HCV sero-positivity. Figure Figure. Disclosures No relevant conflicts of interest to declare.

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 ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 791-791 ◽  
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 &gt;=15 mg/gram dry liver were significantly more likely to have ALTs &gt;=45 IU/L compared to those with LICs &lt;15 mg/gram (5/12 vs. 1/18; odds ratio 12.1; 95% CI 1.2–123.6; p=0.03). Pts with LIC &gt;=15 mg/gram and ALT &gt;=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 &gt;=15 mg/gram had SFs &lt;2000 ng/ml. 55% (11/20) of pts with repeated LICs, had last LICs &lt;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 (&lt;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.

Long Term Erythrocytapheresis Is Associated with Reduced Liver Iron Concentration in Sickle Cell Disease

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 4867-4867
Author(s):  
Scott N. Myers ◽  
Ryan Eid ◽  
John Myers ◽  
Salvatore J. Bertolone ◽  
Ashok B. Raj
Keyword(s):  
Iron Overload ◽  
Serum Ferritin ◽  
Iron Concentration ◽  
Iron Chelation ◽  
Cell Disease ◽  
Liver Iron ◽  
Serial Serum ◽  
Low Levels ◽  
The Impact

Abstract Background: Observational studies and randomized clinical trials have demonstrated that RBC transfusions can alleviate or prevent many complications of sickle cell disease (SCD). Obligatory iron loading is most problematic for those receiving chronic simple transfusions and is managed with chelation therapy to prevent hepatic, cardiac, and endocrinologic complications. Erythrocytapheresis procedures are increasingly used in SCD as they achieve dilution of hemoglobin S without significantly raising the total hematocrit. Some guidelines for the management of iron overload use serum ferritin levels, but non-invasive measurements of liver iron concentration (LIC) using validated and widely available MRI techniques have been described. There is a paucity of data elucidating the impact of long-term erythrocytapheresis (LTE) on LIC. We evaluated LIC with MRI and serial serum ferritin measurements among a population of SCD patients maintained on LTE at a single institution. Methods: Subjects with SCD maintained on the LTE program included those with elevated TCD, history of stroke, recurrent acute chest syndrome, or frequent pain crises unresponsive to hydroxyurea therapy. Serial serum ferritin measurements were followed and chelation with deferasirox was initiated for consistent ferritin level >1000 ng/mL. MRI of liver and cardiac iron was measured on all LTE subjects with non-contrast MRI techniques. A total of n=31 subjects maintained on LTE were enrolled and stratified into two groups: high LIC, ≥5mg/g of dry tissue (n=4, 12.9%) and low LIC, <5mg/g (n=27, 87.1%). Chi-squared and t-test were used to test for differences between the two groups. Logistic regression was used to test what impacted the odds of having a high LIC, while generalized linear mixed-effects modeling was used to test what impacted LIC. Results: None of the subjects had high cardiac iron concentration. Subjects with high LIC were significantly older (17.8 vs. 13.1, p=0.032) and were more likely to be female (100% vs. 44.4%, p=0.038). The duration of LTE was not associated with high and low levels of LIC (8.25 vs. 6.15, p=0.240, Figure 1), levels of LIC (r=0.247, p=0.188, Figure 2), or serum ferritin (r=0.077, p=0.680). The total number of simple of transfusions was not associated with serum ferritin (r=-0.177, p=0.558) or LIC (r=-0.022, p=0.910). Serum ferritin was not significantly associated with LIC (r=0.296, p=0.112, Figure 3). One of the 4 patients with high LIC required chelation with deferasirox for ferritin >1000 ng/mL. Three of the 31 subjects required iron chelation with deferasirox. Conclusions: There was no significant correlation between duration of LTE and LIC. The impact of cumulative simple transfusions on LIC was obviated by maintenance LTE. These findings are consistent with reports that LTE is associated with reduced transfusional iron overload. The lack of significant association between serum ferritin and LIC suggest that validated MRI measurements of LIC may have greater sensitivity for identifying patients with iron overload and guidelines for iron chelation should consider LIC rather than serum ferritin alone. Figure 1. Duration of LTE (years) was not associated with high and low levels of LIC. Figure 1. Duration of LTE (years) was not associated with high and low levels of LIC. Figure 2. Duration of LTE was not associated with levels of LIC. Figure 2. Duration of LTE was not associated with levels of LIC. Figure 3. Serum ferritin was not significantly associated with LIC. Figure 3. Serum ferritin was not significantly associated with LIC. Disclosures No relevant conflicts of interest to declare.

scholarly journals Increased Liver Iron Concentration (LIC) in Adults with Non-Transfusion Dependent Sickle Cell Disease (NTD-SCD): Correlation with Serum Ferritin Concentrations

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 4594-4594
Author(s):  
Mohamed A. Yassin ◽  
Ashraf Tawfiq Soliman ◽  
Vincenzo Desanctis ◽  
Abdulqadir Nashwan ◽  
Abbas Moustafa ◽  
...  
Keyword(s):  
Iron Overload ◽  
Serum Ferritin ◽  
Research Funding ◽  
Iron Concentration ◽  
Hepatic Enzymes ◽  
Cell Disease ◽  
Liver Iron Concentration ◽  
Liver Iron ◽  
Liver Iron Content ◽  
High Liver

Abstract Introduction: Hepatic iron concentration (HIC) is used as a surrogate for total iron balance to guide chelation therapy in transfusion-dependent and independent patients. Unfortunately, liver biopsy is invasive and provides only indirect information regarding other organ systems. FerriScanprovides an accurate validated measurement of liver iron concentration (LIC) through a non-invasive, using patented R2-MRI imaging technology. Aim: To determine the iron status of 11 patients with non-transfusion dependent (NT) patients with sickle cell disease (SCD). Patients and methods: FerriScan (a quick, easy and painless, with an MRI scan time of only two minutes) is used to determine LIC in eleven adults with NT-SCD. Serum ferritin, iron concentrations and hepatic enzymes (ALT and AST) concentrations and total iron binding capacity (TIBC) were measured. Results: 11 adults with NT-SCD were studied. Three had serum ferritin > 500 umol/L , 2 out of the three (ferritin level 1138 and 531 ug/L) had high liver iron measured by ferriScan (> 30 mmol/kg dry tissue). One patient had high liver iron content despite a concomitant serum ferritin concentration = 237 ug/L. On the other hand a patient had serum ferritin = 1117 ug/L while his liver iron was still (27 mmol/kg dry tissue) in the normal range. Serum ferritin concentrations were correlated significantly with liver iron content measured by ferriScan (r = 0.47, p = 0.05). (fig) Three patients had elevated liver enzymes (ALT and AST). Neither serum ferritin, nor LIC was correlated significantly with hepatic function. Discussion: In this study significant number of patients with ND-SCD had high LIC and high serum ferritin and hepatic enzymes (ALT and AST). Elevated levels of LIC and ferritin impose high risk for hepatic disease and cardiac toxicity in these patients. Evidence suggests that patients with high LIC have higher risk of liver fibrosis and cirrhosis as a result of iron overload. In addition, Liver iron concentration (LIC) over 15.0 mg Fe/g dry weight is associated with increased risk of cardiac diseases. Moreover, the liver is considered the early warning system against later endocrine complications, due to iron overload. For NT-SCD, with increased LIC, effective management of liver iron concentration is critical to ensure risk of morbidity due to iron overload is minimized Summary: This is the first study that document increased iron overload in NT-SCD patients. Therefore, we recommend measuring serum ferritin and LIC in NT-SCD patients. Those with increased LIC and/or ferritin should be chelated to prevent long term complications of iron overload.Table.Ageserum FeTIBCFerritinliver ironALTASTyrumol/Lumol/Lug/Lmmol/kgU/LU/L32.323.755.7361.731.024.236.114.217.78.4405.717.716.422.3 Disclosures Nashwan: HMC MRC: Research Funding. Moustafa:HMC MRC: Research Funding. Elomry:HMC MRC: Research Funding.

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.

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