Liver Histology, Liver Iron Concentration (LIC), and Serum Ferritin in a Large Cohort of Chronically Transfused Children with Sickle Cell Anemia: Limitations of LIC As a Marker for Hepatic Injury and Ferritin as An Indicator for Chelation Initiation

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 2142-2142
Author(s):  
Erika Vogel ◽  
Jeffrey D. Lebensburger ◽  
Shuting Bai ◽  
Naomi Fineberg ◽  
Lee Hilliard ◽  
...  
Keyword(s):  
Liver Biopsy ◽  
Sickle Cell ◽  
Serum Ferritin ◽  
Sickle Cell Anemia ◽  
Chelation Therapy ◽  
Iron Concentration ◽  
Dry Weight ◽  
Surrogate Markers ◽  
Transfusion Therapy ◽  
Lobular Inflammation

Abstract Abstract 2142 Chronic blood transfusion therapy reduces clinical events and prevents recurrent brain injury in children with sickle cell anemia. The benefit of administering chronic transfusion is weighed against the risk of an increased iron burden leading to chronic organ injury. The gold standard technique for evaluating the adverse effect of iron is to perform a liver biopsy for quantification of hepatic iron content and evaluation of liver pathology. Surrogate evaluations for iron overload include monitoring liver enzymes, serum ferritin and performing r2* MRI of the liver. In order to evaluate the role for utilizing surrogate markers to monitor liver injury, we conducted a retrospective review of 262 liver biopsies in 109 children with sickle cell anemia on chronic transfusion therapy over a nine year period at a single center. Ninety one patients had HbSS, 17 had HbSB0 thalassemia, and one patient had HbSD. Chronic transfusion therapy was performed by either simple transfusion (65%) or erythrocytapheresis (35%) primarily for stroke prevention (n=236), with a few for other indications (n=26) including lung injury and acute vascular necrosis. Patients were initiated on chronic transfusion at a mean age of 6.2 ± 3.6 yrs (0.75–17yrs) with initial biopsy obtained at a mean age of 14.6 ± 5.3 yrs (3–34 yrs). Chelation with deferoxamine or deferasirox was determined by the physician with a practice standard of initiation of chelation once ferritin increased to > 1000ng/mL. All patients at the time of liver biopsy were treated with chelation therapy with either deferoxamine (30%) or deferasirox (70%). Two pathologists reviewed the biopsies and utilized a standardized hepatic scoring system to evaluate the degree of portal/periportal and lobular inflammation and hepatic fibrosis (0= none, 1= mild, 2= moderate, 3= severe). Portal/periportal inflammation was scored 0–3 respectively in 132, 89, 38, and 0 patients and lobular inflammation in 29, 226, 4, and 0 patients. Fibrosis was scored 0–3 respectively in 23, 107, 103, and 26 patients. Ferritin and ALT were recorded prior (median of 3 days) to the liver biopsy. Seven biopsies performed as part of a therapeutic clinical trial were excluded from this analysis. Results show that the mean (± SD) serum ferritin, liver iron concentration (LIC), and ALT were 3509 ± 2617ng/mL, 17.12 ± 13.0 mg Fe/gm dry weight, and 40.2 ± 40.2 IU/L. With respect to histology, ferritin and LIC levels were significantly increased with higher periportal inflammation score (F= 21, p<0.001. F= 20, p<0.001) and severe fibrosis (score 3) (F=36, p<0.001, F=10.4, p<0.001), but not for lower fibrosis scores (0–2), or lobular inflammation score (p=0.20). Despite this significant histologic correlation with surrogate markers, individual overlap exists between ferritin, LIC and liver pathology. A strong linear correlation exists between ferritin and LIC (r=0.74, p<0.001) but with a spread in LIC (R2=55%). With respect to ferritin as a predictor of LIC, all patients with ferritin >1000ng/mL, a standard value for initiation of chelation therapy, had abnormally high LICs, and surprisingly 11 patients were identified with an abnormal LIC despite a ferritin <1000ng/ml. Furthermore, patients with a high LIC (≥ 7 mg Fe/gm dry weight) demonstrate a significantly higher ferritin as compared to patients with lower LIC< 7 (p<0.001) and this positive relationship between LIC and ferritin was replicated in a population with a higher LIC (LIC ≥ 30mg Fe/g dry weight vs. <30) (p<0.001). ROC curves demonstrate an AUC of.88 ± 0.02 (p<0.001) utilizing a LIC of ≥7 or <7 and 0.91± 0.02 (p<0.001) utilizing a LIC of ≥30 or <30. A weak association was noted between ferritin and alanine aminotransferase (ALT) (r=0.27, p<0.001, R2=8%). The results show that although strong statistical correlations exist between liver histology and ferritin or LIC, variability exists. Additionally, a ferritin >1000ng/mL always predicts abnormal LIC, but is inadequate as an indicator for initiation of chelation. The results suggest caution when using surrogate markers alone to predict histological changes in the liver and to initiate chelation therapy in individual patients on chronic blood transfusion therapy. Disclosures: Lebensburger: University of Alabama at Birmingham: Employment.

Extrahepatic Iron Deposition In Chronically Transfused Children With Sickle Cell Anemia – Baseline Findings From The Twitch Trial

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 2238-2238 ◽  
Author(s):  
John C. Wood ◽  
Alan Cohen ◽  
Banu Aygun ◽  
Hamayun Imran ◽  
Lori Luchtman-Jones ◽  
...  
Keyword(s):  
Iron Overload ◽  
Sickle Cell ◽  
Sickle Cell Anemia ◽  
Research Funding ◽  
Iron Concentration ◽  
Dry Weight ◽  
Iron Deposition ◽  
Liver Iron ◽  
Transfusion Therapy ◽  
Upper Limits

Abstract Introduction Chronic transfusion therapy is the standard of care for children with sickle cell anemia (SCA) and abnormal transcranial Doppler velocities. Although effective, monthly transfusions are costly, inconvenient, and produce iron overload in the liver and extrahepatic organs. The TWiTCH study (ClinicalTrials.gov NCT01425307) is a randomized clinical trial to determine whether hydroxyurea therapy leads to comparable time averaged TCD velocities as conventional transfusion therapy, while reducing somatic iron stores. We report baseline data on iron burden in the spleen, pancreas, and kidneys from the TWiTCH cohort. Methods Pediatric patients from 22 centers underwent screening R2* assessment of the liver, spleen, pancreas, and kidneys. All sites used a 1.5 Tesla magnet, torso phased array coils, and a multiple echo gradient echo sequence with a minimum echo time ≤1.3 ms. Images were analyzed centrally at Children’s Hospital Los Angeles; core laboratory staff were blinded to patient, site, and visit data. Raw R2* values were used as iron surrogates for spleen, pancreas, and kidney. All statistics were performed by the TWiTCH Data Coordinating Center. Results A total of 113/159 enrolled patients (mean age 8.8 ± 6.3 years) successfully completed baseline abdominal R2* assessment (Table 1). Patients had received chronic transfusions for 4.2 ± 2.4 years and iron chelation for 3.2 ± 2.2 years. Serum ferritin values ranged from 191 to 10593 ng/ml (2655.6 ± 1668.1 ng/ml). All subjects had liver iron detectable by R2*, with 51.3% having liver iron concentration (LIC) >7 mg/g, and 13.3% >15 mg/g of dry weight. Splenic R2* could be assessed in 80/113 (71%) subjects, with the remainder having surgical splenectomy or autoinfarction. Splenic R2* revealed splenic tissue was comparable to liver tissue containing on average 13.1 mg Fe/g of dry weight. Pancreas R2* was greater than the upper limits of normal in 39.3% but no values exceeded 100 Hz (the level associated with pancreas dysfunction, pituitary iron accumulation, and cardiac iron deposition in thalassemia patients). LIC was the only significant predictor of pancreas R2* (r2 = 0.06, p=0.001). Kidney R2* was above the upper limits of normal in 79.5% of the patients and demonstrated preferential cortical distribution. Kidney R2* positively correlated with lactate dehydrogenase levels (p < 0.001), positive correlated with LIC R2* (p=0.005) and negatively correlated with hemoglobin level(p = 0.01) with a combined r2 of 0.29. No association was found with total bilirubin or reticulocyte count. Discussion This represents the first multicenter study documenting the prevalence and extent of extrahepatic iron deposition in children with SCA receiving chronic transfusions. Splenic iron deposition was common but uncorrelated with LIC,, suggesting different kinetics of iron loading transport. Clinically-significant pancreatic iron deposition was not observed. Renal R2* tracked with intravascular hemolysis markers, rather than LIC or ferritin, consistent with tubular uptake of filtered cell-free hemoglobin. Overall, chronically transfused children with SCA have greater splenic and renal iron deposition, but much milder pancreatic iron overload, than that observed in transfused thalassemia patients. Disclosures: Wood: Novartis: Honoraria; Apopharma: Honoraria, Patents & Royalties; Shire: Consultancy, Research Funding. Off Label Use: Hydroxyurea is FDA-approved for use in adults but not children. Thompson:Amgen: Research Funding; Eli Lilly: Research Funding; Glaxo Smith Kline: Research Funding; ApoPharma: Consultancy, Honoraria; Novartis: Consultancy, Research Funding; bluebird bio: Research Funding.

scholarly journals JADENU® SUBSTITUTING EXJADE® IN IRON OVERLOADED Β- THALASSEMIA MAJOR (BTM) PATIENTS: A PRELIMINARY REPORT OF THE EFFECTS ON THE TOLERABILITY, SERUM FERRITIN LEVEL, LIVER IRON CONCENTRATION AND BIOCHEMICAL PROFILES

2018 ◽  
Vol 10 ◽  
pp. e2018064 ◽  
Author(s):  
Vincenzo De Sanctis
Keyword(s):  
Iron Overload ◽  
Serum Ferritin ◽  
Serum Ferritin Level ◽  
Chelation Therapy ◽  
Ferritin Level ◽  
Iron Concentration ◽  
Liver Iron Concentration ◽  
Liver Iron ◽  
Transfusion Therapy ◽  
Biochemical Profiles

Abstract. Introduction: Due to the chronic nature of chelation therapy and the adverse consequences of iron overload, patient adherence to therapy is an important issue. Jadenu ® is a new oral formulation of deferasirox (Exjade ®) tablets for oral suspension. While Exjade®  is a dispersible tablet that must be mixed in liquid and taken on an empty stomach, Jadenu ® can be taken in a single step, with or without a light meal, simplifying administration for the treatment of  patients with chronic iron overload. This may significantly improve the compliance to treatment of patients withβ-thalasemia major (BMT). The aim of this study was to evalute the drug tolerability and the effects of chelation therapy on serum ferritin concentration, liver iron concentration (LIC) and biochemical profiles in patients with BMT and iron overload. Patients and Methods: Twelve selected adult patients BMT (mean age: 29 years; range:15-34 years) were enrolled in the study. All patients were on monthly regular packed cell transfusion therapy to keep their pre-transfusional hemoglobin (Hb) level not less than 9 g/dL. They were on Exjade ® therapy (30 mg/kg per day) for 2 years or more before starting Jadenu ® therapy (14-28 mg/kg/day). The reason for  shifting from Deferasirox ® to Jadenu ® therapy was lack of tolerability,  since most of the patients described Deferasirox ® as not palatable. Lab investigations included montly urine analysis and measurement of their serum concentrations of creatinine, fasting blood glucose (FBG), serum ferritin, alkaline phosphatase (ALP), alanine transferase (ALT), aspartate transferase (AST) and albumin concentrations. LIC was measured using FerriScan ®. Thyroid function, vitamin D and serum parathormone, before and one year  after starting  Jadenu ® therapy, were also assessed. Results: Apart from some minor gastrointestinal complaints reported in 3 BMT patients that did not require discontinuation of therapy, other side effects were not registered during the treatment.  Subjectively, patients reported an improvement in the palatability of Jadenu® compared to Exjade ® therapy in 8 out of 12 BMT patients.  A non-significant decrease in LIC and  serum ferritin levels was observed after 1 year of  treatment with Jadenu ® . A positive significant correlation was found between serum ferritin level and LIC measured by FerriScan ® method. LIC and serum ferritin level correlated significantly with ALT level (r = 0.31 and 0.45 respectively, p < 0.05). No significant correlation was detected between LIC and other biochemical or hormonal parameters. Conclusion: Our study shows that short-term treatment with Jadenu ® is safe but is associated with  a non-significant decrease in LIC and serum ferritin levels. Therefore, there is an urgent need for adequately-powered and high-quality trials to assess the clinical efficacy and  the long-term outcomes of new deferasirox formulation.

Barriers to Deferoxamine Adherence for Adults with Sickle Cell Disease.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 3760-3760 ◽  
Author(s):  
Marsha Treadwell ◽  
Jennifer Sung ◽  
Eileen Murray ◽  
Robert Hagar ◽  
Kimberly Major ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Sickle Cell Disease ◽  
Adverse Effects ◽  
Iron Overload ◽  
Sickle Cell ◽  
Serum Ferritin ◽  
Chelation Therapy ◽  
Clinical Care ◽  
Cell Disease ◽  
Transfusion Therapy

Abstract Background: The barriers to adherence with chelation therapy for chronically transfused and iron overloaded patients with sickle cell disease (SCD) have been described only anecdotally. Objectives: To describe barriers to home deferoxamine (DFO) administration adherence among adults with SCD. It was hypothesized that barriers would include limited patient education on the importance of chelation and perceived aversiveness of the regimen. Methods: Medical records were reviewed for 189 adult patients seen at a comprehensive sickle cell center. Patients with transfusion induced hemosiderosis, defined as a serum ferritin ≥ 1500 ng/ml, were administered a four item interview asking if iron overload had ever been discussed with them; if they had been informed they were iron over loaded; if chelation therapy had been offered; and if not currently home chelating, why not. Patients not interviewed were deceased (3); unavailable (10); or declined (3). A study coordinator who did not provide clinical care conducted the interviews. Results: 54 of the 189 patients (29%) had a history of intermittent or chronic transfusion, or pheresis. 45 of these patients were iron overloaded. 29 of these patients agreed to complete the interview; 22 (76%) were female. Average age was 41.5 years (range 22.4 – 58.4 years) and average serum ferritin was 4240.8 (range 1547 – 9420). 23 of the 29 patients (79%) reported that their physician or nurse had discussed iron overload and chelation with them. 16 of these (55%) reported that they were currently receiving home DFO therapy. Reasons given for not administering home DFO included: Reason Number (%) “Don’t want to stick self” 3 (23) No longer being transfused or being exchanged 3 (23) Awaiting clinical trial for oral chelator 2 (15) Home situation too complex 2 (15) Don’t want to (no further explanation) 2 (15) Too many adverse effects 1 (8) Discussion: Life threatening levels of iron overload were observed in intermittently transfused adult sickle cell patients. Contrary to expectations, iron overload and its treatment had been discussed with most patients. However, just over half were currently chelating at home. Toxicity of DFO and misunderstanding that iron overload is no longer a problem if chronic transfusion therapy stops are the most common reasons for non-compliance. Repeated patient counseling are essential in order to prevent progressive iron toxicity in sickle cell disease. Reason Number (%) “Don’t want to stick self” 3 (23) No longer being transfused or being exchanged 3 (23) Awaiting clinical trial for oral chelator 2 (15) Home situation too complex 2 (15) Don’t want to (no further explanation) 2 (15) Too many adverse effects 1 (8)

Serum Ferritin and Liver Iron Concentration in Patients with Iron Overload.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 3833-3833
Author(s):  
Zahra Pakbaz ◽  
Roland Fischer ◽  
Ellen Fung ◽  
Peter Nielsen ◽  
Rainer Engelhardt ◽  
...  
Keyword(s):  
Iron Overload ◽  
Serum Ferritin ◽  
Chelation Therapy ◽  
Iron Concentration ◽  
Liver Iron Concentration ◽  
Liver Iron ◽  
Transfusion Therapy ◽  
Poor Predictor ◽  
The Individual ◽  
The Relationship

Abstract Despite its limitations, serum ferritin (SF) is commonly used to monitor chelation therapy in primary and secondary hemochromatosis. To better predict liver iron concentration (LIC), we prospectively investigated the relationship between SF and LIC in a total of 421 patients with primary (HFE-1 associated, n=241) or secondary hemochromatosis (n=180), consisting of chronically transfused thalassemia (Tx-Thal: n=89) or sickle cell disease patients (Tx-SCD: n=45) and transfusion independent thalassemia patients (nTx-Thal: n=26). In all patients, LIC was measured by SQUID biosusceptometry. SF correlated with LIC (RS = 0.51–0.83, p &lt; 0.001) but was a poor predictor for LIC. SF was significantly lower (p &lt; 0.001) in nTx-Thal and HFE-1 patients despite similar LIC (421 – 5524 μg/g-liver) and it was higher in Tx-SCD compared to Tx-Thal (p = 0.03). In order to improve the value of SF, we calculated the SF/LIC ratio for each group. SF/LIC remained stable over time in patients whose therapy did not change. In iron loaded patients without blood transfusion therapy (nTx-Thal and HFE-1), the median SF/LIC ratio was significant lower (0.32 and 0.43) as compared to transfused patients (Tx-Thal: 0.87, HCV-Thal: 0.99, Tx-SCD: 1.2), probably, indicating differences in the secretion of ferritin into plasma. We conclude that SF alone can mislead the iron unloading therapy as it underestimates LIC in nTx-Thal patients and overestimates LIC in Tx-SCD patients. Once the initial LIC value is obtained and the individual SF/LIC ratio is determined in a patient, the ratio together with SF may be more useful than SF alone to monitor iron overload and predict LIC.

Adults with Severe Sickle Cell Anaemia and Iron Overload Have a High Incidence of Osteopenia and Osteoporosis.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 1684-1684 ◽  
Author(s):  
Farrukh T. Shah ◽  
Ratna Chatterjee ◽  
Matilda Owusu-Asante ◽  
John B. Porter
Keyword(s):  
Vitamin D ◽  
Parathyroid Hormone ◽  
Iron Overload ◽  
Sickle Cell ◽  
Serum Ferritin ◽  
Chelation Therapy ◽  
Iron Chelation ◽  
Dry Weight ◽  
Iron Chelation Therapy ◽  
Liver Iron

Abstract Background: There is very little published data on osteopenia or osteoporosis in patients with sickle cell disorders (SCD) with only occasional case reports that have noted osteopenia in individual SCD patients. It is known that individuals of Afro-Caribbean decent have on average higher BMD scores then age matched Caucasian controls. The causes for bone demineralisation in SCD may be multifactoral. Putative contributory mechanisms include; marrow expansion, bone infarction, delayed puberty from anaemia, low vitamin D, iron overload from blood transfusion, iron chelation therapy, and hypogonadism. Methods and Findings: 17 consecutive SCD patients who had previously been transfused or were currently on a transfusion programme underwent DEXA scanning using a Hologic QDR 4500A. Hypogonadism was assessed for in all patients as well as Vitamin D3, parathyroid hormone (PTH), serum ferritin and haemoglobin levels. 11 of the 17 patients had undergone MRI to assess liver iron. Of 10 females, 6 had osteopenia (Z >−1.0, n= 4) or osteoporosis ( Z >−2.0, n=2) in the spine compared to age matched caucasian controls (p=0.008). In contrast, only 4 had significant hip demineralisation; 2 patients had osteoporosis and 2 were osteopenic. All patients with hip osteopenia also had spinal osteopenia. Liver iron concentration was significantly higher in the osteopenic (9.4mg/g dry wt) than the non-osteopenic group (1.95mg/g dry wt) (p=0.01). Mean serum oestradiol levels were no different between the osteopenic (235 pmol/L) and the non osteopenic patients (287 pmol/L). No differences in ferritin, units of blood transfused, parathyroid hormone or vitamin D level were seen. Only 2 females had received iron chelation with deferrioxamine one of whom was osteopenic. Among 7 males, 2 had spinal osteopenia (mean Z score −1.4) (p= 0.05) but none had osteopenia of the hip. The liver iron was higher in the osteopenic males (mean 12.9 mg/g dry weight) than in the non osteopenic group (mean 2.32 mg/g/dry weight) (p <0.05). Serum ferritin was also higher in osteopenic patients (mean 3729ug/l) than the non-osteopenic group (mean 745ug/l) (p=0.008). No significant difference between the serum testosterone and units of blood transfused, parathyroid hormone or vitamin D level was seen. Only one of the patients had received iron chelation and he was not osteopenic. Among all patients together, there was no evidence on MRI of increased cardiac iron but there was evidence of hypogonadothrophic hypogonadism is 1 female, while the remainder were not hypogonadal. There was evidence of disturbance of the Calcium- Vitamin D- PTH axis in 2 patients (1 male,1 female) both of whom were osteopenic. Conclusion: Osteopenia is a surprisingly common in adult patients with sickle disorders; 47% of patients had osteopenia. Iron loading may be a relevant contributing factor as liver iron was significantly greater in osteopenic than non-osteopenic patients. Hypogonadism and iron chelation therapy can be reasonably excluded as contributory facors in most patients but should be monitored in all patients on transfusion programmes.

Iron Chelation Therapy with Deferasirox (Exjade®, ICL670) or Deferoxamine Results in Reduced Hepatocellular Inflammation and Improved Liver Function in Patients with Transfusion-Dependent Anemia.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 823-823 ◽  
Author(s):  
P. Brissot ◽  
B. Turlin ◽  
G.L. Forni ◽  
G. Alimena ◽  
G. Quarta ◽  
...  
Keyword(s):  
Liver Function ◽  
Liver Biopsy ◽  
Serum Ferritin ◽  
Liver Tissue ◽  
Chelation Therapy ◽  
Iron Concentration ◽  
Iron Chelation ◽  
Iron Chelation Therapy ◽  
Hepatocellular Injury ◽  
Liver Iron

Abstract Transfusional hemosiderosis is often associated with hepatic siderosis or infection with hepatotropic viruses, resulting in hepatocellular injury and progression to chronic liver disease. Liver biopsy is the method of choice for directly assessing damage; scales have been developed to measure necroinflammatory activity (grading) and tissue fibrosis (staging). Iron chelation therapy is historically known to decrease morbidity associated with hepatosiderosis. Aim: To assess 1 year’s chelation therapy with the novel once-daily oral chelator, deferasirox (DSX), or the current standard deferoxamine (DFO), on pathology of liver tissue in chronically transfused patients. Methods: Liver biopsy was performed at baseline and after 1 year in patients participating in DSX Studies 0107 (n=454) and 0108 (n=101). All patients, except 25 in 0107 and 3 in 0108, had liver tissue evaluated by pathology. In 0107, patients with β-thalassemia were randomized to DSX (5, 10, 20 or 30 mg/kg/day; n=224) or DFO (&lt;25, 25–35, 35–50 and ≥ 50 mg/kg; n=230) according to baseline liver iron concentration (LIC). In 0108, patients with β-thalassemia unable to be treated with DFO (n=61) and patients with rare anemias (MDS, DBA and others) (n=40) were enrolled and received DSX only. Grading and staging were determined from biopsy by the Ishak method; LIC was measured in parallel by atomic absorption spectrometry. Results: DSX and DFO dose-dependently affected grading, which mirrored effects on LIC and serum ferritin. DSX 5 and 10 mg/kg increased these parameters, while stabilization and decreases were seen with the highest doses of both chelators, regardless of hepatitis C status. In 0107, a decrease in mean ±SD necroinflammatory score was noted with DSX 30 mg/kg (2.5 ±1.6 to 1.7 ±1.3, n=95) and DFO ≥ 50 mg/kg 5 days/week (2.1 ±1.6 to 1.4 ±1.3, n=95). Similar results were observed in 0108 for β-thalassemia (2.4 ±1.7 to 1.7 ±1.6, n=58) and rare anemia patients (1.8 ±1.5 to 1.5 ±1.3, n=40). This decrease was accompanied by dose-dependent modification of available liver enzyme levels in 0107 (Table); with a similar trend in 0108. No obvious modification of staging was observed after 1 year of treatment, suggesting that longer time periods are needed to observe potential reversal of fibrosis. Change in liver enzymes (ALT; U/L) by treatment (Study 0107) DSX, mg/kg DFO, mg/kg 5 10 20 30 &lt;25 25–35 35–50 ≥ 50 n=8 n=43 n=64 n=107 n=6 n=28 n=88 n=107 Mean ± SD 34.9 21.9 3.6 −2.8 −13.9 −3.7 −2.8 −12.4 ±35.1 ±25.2 ±28.7 ±79.3 ±29.7 ±17.6 ±20.7 ±38.6 Median (range) 36.8 10.0 0.5 −8.0 −10.8 −1.8 −0.8 −9.5 (−19.0, 101.5) (−7.5, 105.0) (−111.5, 91.0) (−143.0, 711.0) (−61.0, 27.0) (−55.5, 32.0) (−93.5, 70.5) (−171.0, 193.3) Conclusions: Although the data show considerable variability, results suggest that chelation therapy with DSX or DFO is associated with reduced hepatocellular inflammation and improved liver function. These modifications appear to be linked with effects on LIC and serum ferritin levels.

Hepatic Iron Overload in Children With Sickle Cell Anemia on Chronic Transfusion Therapy

2009 ◽  
Vol 31 (5) ◽  
pp. 309-312 ◽  
Author(s):  
Kathy Brown ◽  
Charu Subramony ◽  
Warren May ◽  
Gail Megason ◽  
Hua Liu ◽  
...  
Keyword(s):  
Iron Overload ◽  
Sickle Cell ◽  
Sickle Cell Anemia ◽  
Hepatic Iron ◽  
Transfusion Therapy ◽  
Hepatic Iron Overload

Unexpected Anemia and Reticulocytopenia in an Adolescent With Sickle Cell Anemia Receiving Chronic Transfusion Therapy

2015 ◽  
Vol 37 (7) ◽  
pp. e438-e440
Author(s):  
Emily R. Blauel ◽  
Lily T. Grossmann ◽  
Madhav Vissa ◽  
Scott T. Miller
Keyword(s):  
Sickle Cell ◽  
Sickle Cell Anemia ◽  
Transfusion Therapy

STUDIES OF CONGENITAL HEMOLYTIC SYNDROMES

PEDIATRICS ◽  
1958 ◽  
Vol 22 (5) ◽  
pp. 910-922
Author(s):  
Marion E. Erlandson ◽  
Irving Schulman ◽  
Gertrude Stern ◽  
Carl H. Smith
Keyword(s):  
Sickle Cell ◽  
Sickle Cell Anemia ◽  
Fetal Hemoglobin ◽  
Severe Form ◽  
Intermediate Form ◽  
Transfusion Therapy ◽  
Effective Synthesis ◽  
Cooley's Anemia ◽  
Compensation Index

Rates of destruction of erythrocytes and of effective production of erythrocytes and hemoglobin have been determined in 10 patients with homozygous Cooley's anemia. The method employed was based upon survival of Cr51-labeled cells in patients in whom a state of equilibrium of erythrocytes was present. While a marked hemohytic defect is present, this defect does not, by itself, determine the degree of anemia present. Rates of effective production of erythrocytes are increased above normal but are not increased to the same degree found in patients with other hemolytic diseases. Rates of effective synthesis of hemoglobin were found to be less than those obtained for production of erythrocytes. The rates of production of fetal hemoglobin in these patients are remarkably elevated but cannot be directly correlated with the rate of destruction of erythrocytes, rate of production of erythrocytes, or the degree of anemia present. The hemolytic defect in patients with intermediate Cooley's anemia was comparable to that in the majority of the patients with the severe form of disease. However, the most marked hemolytic defects were among patients with the severe and not with the intermediate form of disease. Production of erythrocytes and hemoglobin did not differ significantly in the two forms of this disease. Results in two splenectomized patients did not differ significantly from results in the non-splenectomized group of patients. However, since pre-splenectomy data were not available, no statement may be made as to possible individual benefit derived from the operation. The final status of each patient is determined by the particular balance obtained between rates of destruction and production. Neither production nor destruction alone determines the degree of anemia. The compensation index, as a measure of final status in each patient, was lowest in the severe form of Cooley's anemia. It is presumed to be lower still in many patients who could not be studied because transfusion therapy was in progress. The compensation index is somewhat higher in patients with intermediate Cooley's anemia and in two splenectomized individuals not requiring frequent transfusions. Values in these patients approach the higher levels found in patients with sickle cell anemia and congenital spherocytosis.

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