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

scholarly journals Transfusional iron overload in children with sickle cell anemia on chronic transfusion therapy for secondary stroke prevention

2011 ◽  
Vol 87 (2) ◽  
pp. 221-223 ◽  
Author(s):  
Janet L. Kwiatkowski ◽  
Alan R. Cohen ◽  
Julian Garro ◽  
Ofelia Alvarez ◽  
Ramamorrthy Nagasubramanian ◽  
...  
Keyword(s):  
Iron Overload ◽  
Sickle Cell ◽  
Sickle Cell Anemia ◽  
Stroke Prevention ◽  
Secondary Stroke Prevention ◽  
Transfusion Therapy

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.

Hemoglobin Α Clearance Is Associated with RBC Antibodies in Chronically Transfused Children with Sickle Cell Anemia

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 3839-3839
Author(s):  
Marianne Elaine McPherson Yee ◽  
Cassandra Josephson ◽  
Anne M. Winkler ◽  
Paula L. Jessup ◽  
Sean R. Stowell ◽  
...  
Keyword(s):  
Iron Overload ◽  
Board Of Directors ◽  
Sickle Cell ◽  
Sickle Cell Anemia ◽  
Advisory Committees ◽  
Total Blood ◽  
Transfusion Therapy ◽  
The Mean ◽  
Clinically Significant ◽  
Erythrocyte Antigen

Abstract Chronic transfusion therapy (CTT) for sickle cell anemia (SCA) reduces the risk of sickle complications by diluting hemoglobin S (HbS)-containing red blood cells (RBCs) with HbA RBCs and suppressing sickle erythropoiesis. HbS level is influenced by both endogenous hemolysis and clearance of transfused RBC. Minor RBC antigen (Ag) mismatches may result in alloimmunization and hemolytic reactions, but it is unknown if Ag mismatches independently influence HbA clearance. This study sought to: (1) determine the frequency of RBC minor Ag mismatches that occur in chronically transfused SCA patients receiving phenotype-matched transfusions; (2) determine the rate of clearance of transfused HbA following each transfusion; (3) explore associations of HbA clearance with RBC minor Ag mismatches. Children with SCA ages 3-20 years on CTT by either simple transfusions or partial manual exchange (PME) were enrolled in a prospective observational study. All RBC units were serologically matched for C/c, E/e, K (category 1); additional matching for Fya, Jkb, and Ag-negative for putative antibodies (category 2) was provided to patients with ≥1 clinically significant alloantibody or (in some cases) warm autoantibodies. RBC genotyping of SCA patients was performed using PreciseType™ Human Erythrocyte Antigen (HEA), RHCE, and RHD BeadChip assays (Immucor, Norcross, GA). Genomic DNA was extracted from unit segments of all RBC transfused over 12 months and tested using the prototype HEA Leukoreduced (HEA-LR) BeadChip assay to detect the same profile of RBC Ag. RH variant testing of units was not performed. Pre-transfusion HbA was recorded for all episodes, where HbA (g/dL) = Hb (g/dL) x HbA%. Hb electrophoresis was drawn 15-30 minutes post-transfusion in a subset of episodes. For other episodes, post-transfusion HbA was estimated based on the volume of transfusion (VolT), estimated unit hematocrit (Hct), phlebotomy volume (VolPh, if applicable) and total blood volume (TBV), using the following equation: Post HbA (g/dL) = Pre HbA (g/dL) + [(unit Hct) x VolT / 3 x Wt] - (Pre HbA%/100) x [(Pre Hb (g/dL) x VolPh / 3 x TBV]. HbA loss/day was calculated from the Post HbA to the next pre-transfusion HbA. There were 82 patients (54 category 1, 28 category 2) who received 2123 units in 1014 transfusion episodes; HEA-LR genotypes were obtained on 1827 units and 828 complete transfusion episodes. Altered RHC/c or e genotypes were present in 29 (36%), and partial D+ genotypes in 4 (5%). There were 46 historical alloantibodies, the majority against Rh (C, E, hrB, Goa, f, V, VS) and Kell (K, Kpa, Jsa). During the study, 5 patients developed 6 new alloantibodies: 3 Jsa, 1 Goa, 1 Wra, 1 AUS (category 2 transfusions alloantibody incidence 0.64/100 units; category 1 transfusions 0.074/100 units). The mean genotype-predicted Ag mismatches per transfusion was 3.52 for category 1 and 2.78 for category 2 (despite category 2 being matched for ≥2 Ags beyond category 1 matching). Ag mismatch frequency was different in category 1 vs. 2 transfusions for: C (3.8% vs. 0%, p=0.0009), e (24.5% vs. 36.8%, p=0.0002), and VS (21.2% vs. 13.6%, p=0.008). Overall concordance between HEA-LR and available serologic testing was 98%. Of the 169 transfusion episodes with post-transfusion HbA measurements (103 category 1, 66 category 2), the mean HbA loss was 2.38 g/dL/28 days for category 1 vs. 2.73 g/dL/28 days for category 2 (p=0.0047). Comparison of category 1 vs. 2 transfusions (see table) shows shorter transfusion interval and higher frequency of PME in category 2 transfusions. Estimated post HbA had a bias of -0.31 g/dL (95% C.I.-0.18, -0.46) and precision of 0.85 g/dL (95% C.I. 0.61, 1.18). Comparison of estimated HbA loss to Ag mismatches was limited to 533 transfusion episodes in which unit Hct could be estimated within &lt;10% range. Estimated HbA loss had a small negative correlation with Ag mismatches for category 1 (r= -0.123, p=0.027) but not for category 2 transfusions. In linear regression, the only Ag associated with increased HbA loss was N which was limited to category 1 transfusions (p=0.027). HbA loss did not correlate with age of units. This is the first report to characterize RBC minor Ag mismatches in SCA patients on CTT receiving limited vs. extended phenotypically matched RBCs. These findings suggest that clearance of transfused RBCs may be influenced by the patient's history of immunologic response to RBC Ag rather than total or specific Ag mismatches. Table Table. Disclosures Josephson: Octapharma: Consultancy; Immucor: Consultancy; Biomet Zimmer: Consultancy. Winkler:Cerus Corporation: Honoraria; Siemens Healthcare Diagnostics, Inc.: Honoraria; Instrumentation Laboratory: Employment, Honoraria, Membership on an entity's Board of Directors or advisory committees; Grifols: Membership on an entity's Board of Directors or advisory committees; HemoCue America: Membership on an entity's Board of Directors or advisory committees. Fasano:Terumo BCT: Other: educational speaking (non-branded) on Iron overload in SCD; Novartis: Membership on an entity's Board of Directors or advisory committees, Other: educational speaking (non-branded) on Iron overload in SCD; Apopharma: Membership on an entity's Board of Directors or advisory committees; Immucor: Membership on an entity's Board of Directors or advisory committees.

Abstract #914: Polyglandular Autoimmune Syndrome in a Patient with Sickle Cell Anemia and Iron Overload

2005 ◽  
Vol 11 ◽  
pp. 85
Author(s):  
Allison Elise Kerr ◽  
Wolali Odonkor ◽  
Gail Nunlee-Bland ◽  
Juanita Archer ◽  
Anitha Kolukula ◽  
...  
Keyword(s):  
Iron Overload ◽  
Sickle Cell ◽  
Sickle Cell Anemia ◽  
Polyglandular Autoimmune Syndrome ◽  
Autoimmune Syndrome

scholarly journals Free‐breathing mapping of hepatic iron overload in children using 3D multi‐echo UTE cones MRI

2021 ◽  
Vol 85 (5) ◽  
pp. 2608-2621 ◽  
Author(s):  
Youngwook Kee ◽  
Christopher M. Sandino ◽  
Ali B. Syed ◽  
Joseph Y. Cheng ◽  
Ann Shimakawa ◽  
...  
Keyword(s):  
Iron Overload ◽  
Free Breathing ◽  
Hepatic Iron ◽  
Hepatic Iron Overload

Pathology of Hepatic Iron Overload

2005 ◽  
Vol 25 (04) ◽  
pp. 392-401 ◽  
Author(s):  
Elizabeth M Brunt
Keyword(s):  
Iron Overload ◽  
Hepatic Iron ◽  
Hepatic Iron Overload

Magnetic resonance imaging of transfusional hepatic iron overload

1994 ◽  
Vol 67 (796) ◽  
pp. 339-341 ◽  
Author(s):  
S Bondestam ◽  
A Lamminen ◽  
V-J Anttila ◽  
T Ruutu ◽  
P Ruutu
Keyword(s):  
Magnetic Resonance Imaging ◽  
Magnetic Resonance ◽  
Iron Overload ◽  
Hepatic Iron ◽  
Resonance Imaging ◽  
Hepatic Iron Overload
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