Intravenous (IV) Iron Supplementation in Patients with Chemotherapy-Induced Anemia (CIA) Receiving Darbepoetin alfa Every 3 Weeks (Q3W): Iron Parameters in a Randomized Controlled Trial.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 1552-1552 ◽  
Author(s):  
Christian Lerchenmueller ◽  
Faress Husseini ◽  
Bernd Gaede ◽  
Tony Mossman ◽  
Tamas Suto ◽  
...  
Keyword(s):  
Serum Ferritin ◽  
Darbepoetin Alfa ◽  
Iron Supplementation ◽  
Transferrin Saturation ◽  
Oral Iron ◽  
Ferritin Concentration ◽  
Standard Practice ◽  
Serum Ferritin Concentration ◽  
Iv Iron ◽  
Iron Parameters

Abstract Background and Aim: The role of IV iron supplementation during treatment with erythropoiesis-stimulating agents (ESAs) in patients with CIA is of increasing interest as a possible means of improving response. This randomized, open-label, multicenter study was designed to evaluate the safety and efficacy of IV iron vs standard practice in CIA patients receiving darbepoetin alfa. Interim efficacy analyses showed a higher response rate for darbepoetin alfa with IV iron compared to darbepoetin alfa with standard iron practice with no difference in the safety profile between the treatment arms (Vanderbroek et al, EHA 2006). Iron parameters are reported here. Methods: Eligible patients were diagnosed with a non-myeloid malignancy and had CIA with a baseline hemoglobin (Hb) value < 11g/dL. All patients received darbepoetin alfa 500 mcg administered Q3W with the SureClick™ prefilled autoinjector. Patients were randomized 1:1 to IV iron 200 mg (single dose Q3W at the same time as darbepoetin alfa or in 2 doses of 100 mg within 3 weeks) or standard practice (oral iron or no iron). Randomization was stratified by tumor type and baseline Hb category (< 10 or ≥10 g/dL). Results: A total of 400 patients were randomized. Mean (SD) age of the study population was 61.4 (11.5) years; range, 20–86. Sixty percent (n=241) of participants were women; 28% (n=114) had lung or gynecological tumors; and 52% (n=208) had a baseline Hb value ≥10 g/dL. In the interim analysis population (n=196), the mean (SD) weekly dose of IV iron was 64.8 (6.6) mg in the IV iron group (n=100). In the standard practice group, 28 of 96 patients (29%) received oral iron and 2 (2%) received IV iron (these patients were analyzed as randomized). Mean (standard error) serum ferritin concentrations and percent transferrin saturation (TSAT) in the 2 groups from baseline (BL) to end of study (EOS) are shown in the figure. Conclusions: The combination of darbepoetin alfa Q3W and IV iron appeared to be associated with a trend toward increased mean serum ferritin levels compared to the standard practice control arm. In contrast, mean TSAT surprisingly appeared to be similar in the 2 groups for most of the study period, perhaps suggesting that TSAT is influenced by other factors. Iron management appears to be an important factor in the response to ESAs and the findings presented here suggest the need for additional exploration into iron uptake and demand in cancer patients treated with darbepoetin alfa. Serum Ferritin Concentration Serum Ferritin Concentration Transferrin Saturation (%) Transferrin Saturation (%)

Changes in iron parameters in patients (pts) with chemotherapy-induced anemia (CIA) receiving darbepoetin alfa (DA) every 3 weeks with and without intravenous iron supplementation

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 19621-19621
Author(s):  
T. Suto ◽  
J. F. Vansteenkiste ◽  
T. Mossman ◽  
T. Pinter
Keyword(s):  
Iron Deficiency ◽  
Serum Ferritin ◽  
Darbepoetin Alfa ◽  
Serum Iron ◽  
Iron Supplementation ◽  
Binding Capacity ◽  
Tumor Type ◽  
Open Label ◽  
Iv Iron ◽  
Iron Parameters

19621 Background: There is growing interest in the use of intravenous (IV) iron supplementation in pts receiving erythropoiesis- stimulating agents (ESAs). We present an exploratory analysis of iron parameters in pts with CIA enrolled in a phase IIIb, randomized, open- label, study of DA administered with either IV iron or oral/no iron. Methods: Eligible pts had a non-myeloid malignancy and CIA (baseline Hb < 11g/dL). Pts received DA 500 mcg every 3 weeks (Q3W) using the Aranesp (darbepoetin alfa) prefilled SureClick autoinjector. Pts were randomly allocated (1:1) to receive either DA + 200 mg IV iron (200 mg Q3W with DA Q3W or two 100 mg doses within 3 weeks) or DA + oral/no iron. Randomization was stratified by tumor type and baseline Hb (< or = 10 g/dL). The primary endpoint was % pts achieving a hematopoietic response (Hb = 12 g/dL or increase = 2 g/dL). Results: 396 randomized pts received 1 dose of DA (IV-iron arm = 200; oral/no-iron arm = 196). Mean (SD) age was 61.0 (11.5) yrs; 61% (n = 240) were women; 28% (n = 111) had lung/gynecological tumors. Pt demographics were similar between arms. 44 (11%) pts had baseline iron deficiency (TSAT < 15%; serum ferritin < 100 μg/L); 5 (2%) in the IV iron arm and 23 (12%) in the oral/no-iron arm developed it. 141 (36%) pts had baseline functional iron deficiency (serum iron < 60 μg/dL; serum ferritin > 20 μg/L; TSAT < 20%); 54 (27%) in the IV arm and 67 (35%) in the oral/no-iron arm developed it. See table for iron parameters. Improved Hb-based responses in the IV-iron arm will be presented. Conclusions: Pts who received DA Q3W + IV iron appeared less likely to develop iron deficiency; iron deficiency may reduce responsiveness to ESAs. These pts also appeared to have a larger increase in mean serum ferritin levels. In contrast, mean serum iron, %TSAT, total iron binding capacity, and reticulocytes appeared to be similar in the 2 arms for most of the study period, suggesting that these iron parameters are not influenced by IV iron. No significant financial relationships to disclose. [Table: see text]

scholarly journals Reduction of tissue iron stores and normalization of serum ferritin during treatment with the oral iron chelator L1 in thalassemia intermedia

Blood ◽  
1992 ◽  
Vol 79 (10) ◽  
pp. 2741-2748 ◽  
Author(s):  
NF Olivieri ◽  
G Koren ◽  
D Matsui ◽  
PP Liu ◽  
L Blendis ◽  
...  
Keyword(s):  
Iron Overload ◽  
Serum Ferritin ◽  
Iron Concentration ◽  
Transferrin Saturation ◽  
Dramatic Improvement ◽  
Thalassemia Intermedia ◽  
Ferritin Concentration ◽  
Iron Stores ◽  
Tissue Iron ◽  
Serum Ferritin Concentration

Abstract In patients with thalassemia intermedia in whom hyperabsorption of iron may result in serious organ dysfunction, an orally effective iron- chelating drug would have major therapeutic advantages, especially for the many patients with thalassemia intermedia in the Third World. We report reduction in tissue iron stores and normalization of serum ferritin concentration after 9-month therapy with the oral chelator 1,2- dimethyl-3-hydroxypyrid-4-one (L1) in a 29-year-old man with thalassemia intermedia and clinically significant iron overload (SF 2,174 micrograms/L, transferrin saturation 100%; elevated AST and ALT, abnormal cardiac radionuclide angiogram) who was enrolled in the study with L1 75 mg/kg/day after he refused deferoxamine therapy. L1-Induced 24-hour urinary iron excretion during the first 6 months of therapy was (mean +/- SD, range) 53 +/- 30 (11 to 109) mg (0.77 mg/kg), declining during the last 3 months of L1 to 24 +/- 14 (13–40) mg (0.36 mg/kg), as serum ferritin decreased steadily to normal range (present value, 251 micrograms/L). Dramatic improvement in signal intensity of the liver and mild improvement in that of the heart was shown by comparison of T1- weighted spin echo magnetic resonance imaging with images obtained immediately before L1 administration was observed after 9 months of L1 therapy. Hepatic iron concentration decreased from 14.6 mg/g dry weight of liver before L1 therapy to 1.9 mg/g liver after 9 months of therapy. This constitutes the first report of normalization of serum ferritin concentration in parallel with demonstrated reduction in tissue iron stores as a result of treatment with L1. Use of L1 as a therapeutic option in patients with thalassemia intermedia and iron overload appears warranted.

Hepatic computed tomography for monitoring the iron status of haemodialysis patients with haemosiderosis treated with recombinant human erythropoietin

1991 ◽  
Vol 81 (1) ◽  
pp. 113-121 ◽  
Author(s):  
Sergio De Marchi ◽  
Emanuela Cecchin
Keyword(s):  
Computed Tomography ◽  
Serum Ferritin ◽  
Recombinant Human Erythropoietin ◽  
Chelation Therapy ◽  
Iron Status ◽  
Transferrin Saturation ◽  
Ferritin Concentration ◽  
Human Erythropoietin ◽  
Serum Ferritin Concentration ◽  
Erythropoietin Treatment

1. A randomized, partial-crossover study was conducted in uraemic patients with dialysis-associated anaemia and transfusional iron overload to evaluate the effects of desferrioxamine chelation therapy and of recombinant human erythropoietin treatment on hepatic iron storage determined by computed tomography, as well as by serum ferritin concentration and transferrin saturation. 2. Twenty-one haemodialysis patients with moderate iron overload, confirmed by values of serum ferritin concentration, transferrin saturation and hepatic computed tomography density exceeding 1000 μg/l, 45% and 68 Hounsfield units respectively, were randomly allocated to three groups and were followed for 12 months. 3. During the first 6 months group 1 (n = 7) received desferrioxamine chelation therapy (30 mg/kg intravenously three times a week) and group 2 (n = 7) underwent recombinant human erythropoietin treatment (36 units/kg intravenously three times a week). Thereafter, in the second 6 months of observation patients in group 1 were switched to receive recombinant human erythropoietin. Because of a poor response in the desferrioxaminetreated group in the initial 6 months, patients in group 2 continued on the maintenance dose of recombinant human erythropoietin (18 units/kg three times a week) until the end of the trial. Patients in group 3 (n = 7) were maintained on placebo throughout the study. 4. In comparison with placebo, recombinant human erythropoietin treatment, but not desferrioxamine chelation therapy, reduced serum ferritin concentration, transferrin saturation and hepatic computed tomography density, and was associated with a rise in haemoglobin and packed cell volume. Hepatic computed tomography density, serum ferritin concentration and transferrin saturation decreased in 13 out of 14 patients (93%) during treatment with recombinant human erythropoietin. However, when the changes in hepatic computed tomography density were compared with those in the biochemical indices, we observed that the decreases in serum ferritin concentration and transferrin saturation were much slower and delayed. More specifically, within 6 months of starting recombinant human erythropoietin treatment, hepatic computed tomography density was normalized in 13 out of 14 patients (93%), whereas serum ferritin concentration and transferrin saturation were within the normal limits in only two (14%) and six patients (43%), respectively. 5. In conclusion, the strategies for monitoring the iron status of haemodialysis patients with transfusional haemosiderosis may evolve to a new level of sophistication with the introduction of computed tomography scanning. This technique has the advantage of estimating directly the effect of recombinant human erythropoietin treatment on hepatic iron storage. Hepatic computed tomography density is complementary to serum ferritin concentration and transferrin saturation in monitoring the iron status of haemodialysis patients treated with recombinant human erythropoietin.

Hereditary Hemochromatosis in an Adult Due to H63D Mutation: The Value of Estimating Iron Deposition By MRI T2* and Dissociation Between Serum Ferritin Concentration and Hepatic Iron Overload

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 4891-4891
Author(s):  
Mohamed A. Yassin ◽  
Ashraf T Soliman ◽  
Vincenzo Desanctis ◽  
Sandara Abusamaan ◽  
Ahmed Elsotouhy ◽  
...  
Keyword(s):  
Iron Overload ◽  
Basal Ganglion ◽  
Serum Ferritin ◽  
Normal Values ◽  
Hereditary Hemochromatosis ◽  
Transferrin Saturation ◽  
Iron Deposition ◽  
Ferritin Concentration ◽  
H63d Mutation ◽  
Serum Ferritin Concentration

Abstract Hereditary hemochromatosis (HH) is an autosomal recessive disorder characterized by excessive intestinal absorption of dietary iron, causing iron overload in different organs, especially the liver. Hemochromatosis may not be recognized until later in life. Patients are usually asymptomatic but may present with a variety of signs and symptoms. These include: hyper-pigmented skin, hepatomegaly, arthralgia, diabetes mellitusand/or heart failure/arrhythmia. The risk of HH related morbidity in HFE compound homozygotes patients (H63D /H63D) is considered rare, we report a male patient with H63D mutation who developed impaired glucose tolerance, and high hepatic enzymes due to significant iron accumulation in the liver as well as Parkinsonian-like syndrome due to iron deposition in the basal ganglia. A 40 year old Qatari male was referred for evaluation of a rise in hemoglobin and hematocrit values with normal MCV, total leucocyte and platelet counts. The patient was asymptomatic with normal vital signs, no depigmentation or hepato-splenomegaly. Hematologic findings included a hemoglobin concentration of Hb 16.5 g/dL, hematocrit 53%, mean corpuscular volume (MCV) 93 fL/red cell, leucocyte count of 7200/ μL and a platelet count of 199000/μL. His serum ferritin was 359 μg/l ( normal values: < 336 μg/l), serum iron: 37 μmol/l ( normal values <28.6μmol/l), fasting transferrin saturation: 64% (normal < 50%). A random glucose 6.5 and 6.4 mmol/L (normal values 5.5mmol/L ), A1C of 5,4 %, normal creatinine and electrolytes, alanine aminotransferase (ALT) of 66 U/l (normal < 40U/l), mild elevation of bilirubin 39 umol/l (normal <24umol/l), normal U&E Hepatitis B and C antibodies were negative. OGTT revealed impaired glucose tolerance. Thyroid function, morning serum cortisol, LH and FSH and serum total testosterone concentrations were in the normal range. A diagnosis of polycythemia vera was excluded on the basis of WHO Criteria 2008. The polymerase chain restriction assay was negative for the common mutation (C282Y) but positive for H63 D mutation. Family screening confirmed HH in his brother (homozygous), whereas his mother, two brothers and the sister were carriers (heterozygous). His four offspring were carriers. This suggested an autosomal recessive mode of inheritance. Conventional MRI study showed a normal liver size with diffuse fatty changes and focal areas of fatty sparing with some evidence of iron deposition. Whereas, T2-star (T2*) sequences showed a diffuse and significant decrease in liver signal intensity. A LIC liver concentration of 27 mg Fe/g dry wt was found (normalvalues:< 2 mg Fe/g dry wt; severe iron overload: ≥15 mg Fe/g dry wt). No significant iron deposition in the spleen, heart or pancreas was observed. At the age of 41 years the patient complained of tremors in both hands and arms while sitting or standing still (resting tremor) that improved with hands movements. A brain MRI revealed iron deposition in the basal ganglion. It was concluded that basal ganglionicn iron deposition mediated the neurological decline. Currently, the transferrin saturation and serum ferritin levels are within normal. Discussion: This is the first case of HH secondary to H63 D among an Arab family and the first reported case of Parkinsonism tremors secondary to this mutation. The H63D HFE variant is less frequently associated with HH, but its role in the neurodegenerative diseases has received a great attention. An accurate evaluation of iron overload is necessary to establish the diagnosis of HH and to guide iron chelation in HH by determination of liver iron concentration (LIC) by means of T2* MRI. Although serum ferritin concentration was only mildly increased a significant siderosis in the liver was detected by MRI T2* technique occurred. Liver siderosis was associated with mild impairment of liver function (increased serum ALT and bilirubin ). Conclusion: Our data further confirm that serum ferritin levels are not an accurate measure of total body iron stores in HH. Iron deposition in the liver and basal ganglion occurred despite mild elevation of ferritin. changes in basal ganglion may present by parkinsonian like tremors in these patients Use,T2* MRI should be encouraged in patients with HH for better evaluation of Iron overload and avoidance of Complications since serum ferritin can be misleading in these conditions. Disclosures Yassin: Qatar National research fund: Patents & Royalties, Research Funding. Aldewik:Qatar Ntional Research Fund: Patents & Royalties, Research Funding.

scholarly journals Iron Age or New Age: Ironing out the Diagnosis of Anaemia of Inflammation from Iron Deficiency Anaemia

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 3354-3354
Author(s):  
Nicola J Svenson ◽  
Russell Patmore ◽  
Heidi J Cox ◽  
James R Bailey ◽  
Stephen Holding
Keyword(s):  
Iron Deficiency ◽  
Serum Ferritin ◽  
Serum Iron ◽  
Iron Status ◽  
Diagnostic Testing ◽  
Transferrin Saturation ◽  
Oral Iron ◽  
Gastrointestinal Disorders ◽  
Serum Hepcidin ◽  
Iron Parameters

Abstract Introduction Iron deficiency anaemia (IDA) and anaemia of chronic inflammation (AI) are the most prevalent causes of iron related anaemia in subjects with gastrointestinal disorders contributing significantly to morbidity and mortality. Diagnosis of IDA and AI is not always straight forward and currently a combination of several serum parameters (ferritin, transferrin, transferrin saturation, iron and C-reactive protein) is required. Subjects with a mixed aetiology can be difficult to interpret using traditional serum parameters, particularly in the presence of an inflammatory process. Hepcidin (a 25 amino-acid peptide hormone) in conjunction with reticulocyte haemoglobin equivalent (RetHe) has the potential to differentiate IDA from AI and in cases of mixed aetiology replacing the traditional laboratory parameters (serum iron, CRP, transferrin saturation and ferritin). Aim The aim of the study was to evaluate the performance of a commercially available ELISA assay and investigate whether hepcidin and RetHe can differentiate AI from mixed aetiology. Method The study investigated 77 patients with gastrointestinal disorders associated with anaemia in a secondary care setting using a traditional pathway of 6 tests (figure 1): Complete Blood Count (CBC), Reticulocytes, serum ferritin, CRP, transferrin, serum Iron. Hepcidin concentration was measured using a commercially available ELISA method (DRG Diagnostic GmbH, Marburg, Germany), CBC and RetHe using a Sysmex XE-2100 CBC analyser, iron parameters and CRP using Beckman Coulter platforms. Results Hepcidin correlated well with ferritin R2 = 0.79, p<0.0001. The results were compared to traditional parameters with Receiver Operator Curves (ROC) used to determine diagnostic cut off concentrations (table 1). Table 1. Sensitivity and specificity of serum ferritin and serum hepcidin used to determine diagnostic cut off values. Selected cut off values IDA AI Serum ferritin 30.0µg/L Sensitivity 83% Specificity 64% Sensitivity 55% Specificity 75% Serum hepcidin 8ng/mL Sensitivity 73% Specificity 72% Sensitivity 70% Specificity 67% Serum hepcidin 40ng/mL Sensitivity 98% Specificity 32% Sensitivity 25% Specificity 91% Ferritin was unable to distinguish IDA from AI in mixed aetiology situations. This gives rise to a new proposed 2 step pathway (figure 2) using 3 tests: CBC, RetHe and hepcidin differentiating IDA from AI in mixed aetiology cases indicating the cause of the anaemia. The RetHe value can then be used to predict the response to oral iron. Conclusion Serum hepcidin may not yet replace serum ferritin as the preferred iron status marker, but in conjunction with RetHe it may distinguish mixed aetiology subjects. This offers the potential development of a clearer clinical pathway for investigation of difficult subjects, including reduction in the number of tests required during anaemia investigations and shorter diagnosis times. The advantage of hepcidin together with RetHe over traditional iron parameters is both as a real time marker of iron status and an indication of likelihood of response to iron therapy. The patient would benefit from a shorter recovery time, unnecessary testing, reduction in ineffective treatment and overall reduction in costs. Figure 1. Current diagnostic testing pathway using 6 independent tests with serum ferritin used as the primary indicator of iron stores. Figure 1. Current diagnostic testing pathway using 6 independent tests with serum ferritin used as the primary indicator of iron stores. Figure 2. Suggestion of a new 2 step diagnostic testing pathway with serum hepcidin as the primary indicator and reticulocyte haemoglobin equivalent as the predictor of iron deficiency and response to oral iron. Figure 2. Suggestion of a new 2 step diagnostic testing pathway with serum hepcidin as the primary indicator and reticulocyte haemoglobin equivalent as the predictor of iron deficiency and response to oral iron. Disclosures Patmore: Janssen: Honoraria; Gilead: Honoraria.

scholarly journals The effect of iron versus iron plus zinc supplementation in children with malaria

2016 ◽  
Vol 46 (1) ◽  
pp. 7 ◽  
Author(s):  
Bugis Mardina Lubis ◽  
Danny Dasraf ◽  
Nelly Rosdiana ◽  
Bidasari Lubis ◽  
Munar Lubis ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Placebo Group ◽  
Serum Ferritin ◽  
Iron Supplementation ◽  
Zinc Supplementation ◽  
Hemoglobin Concentration ◽  
Potential Interaction ◽  
Ferritin Concentration ◽  
Blood Samples ◽  
Serum Ferritin Concentration

Introduction Little is known about the potential interaction of ironand zinc given to increase hemoglobin and serum ferritin in chil-dren with malaria.Objective To study the effect of iron compared with a combination ofiron and zinc supplementation on children with falciparum malaria.Method Children with positive Plasmodium falciparum (n=86) wererandomly assigned to a daily supplementation of 6 mg iron/kg perday plus placebo or plus 10 mg zinc per day for 30 days. All childrenwere treated with the same regimen for the treatment of P. falciparum.Venous blood samples were collected at the start and end of thestudy. After 30 days of supplementation, the baseline and follow-upblood samples were analyzed.Results The increase of hemoglobin concentration in the ironplus placebo group was 0.58 g/dl, while in the iron plus zinc groupwas 0.09 g/dl (P<0.05). Serum ferritin concentration was high inboth groups before trial, yet there was no significant differenceafter iron supplementation.Conclusions Iron supplementation showed significant increasein hemoglobin concentration in children with positive P. falciparumtreated with the same regimen of treatment. Supplementation ofiron alone as well as iron plus zinc had been proven ineffective toiincrease serum ferritin in children with malaria.

scholarly journals Effect of Oral Iron Administration on Mental State in Children With Low Serum Ferritin Concentration

2019 ◽  
Vol 6 ◽  
pp. 2333794X1988481
Author(s):  
Katsunaka Mikami ◽  
Hideki Okazawa ◽  
Keitaro Kimoto ◽  
Fumiaki Akama ◽  
Yuichi Onishi ◽  
...  
Keyword(s):  
Serum Ferritin ◽  
Mental State ◽  
Oral Iron ◽  
Ferritin Concentration ◽  
Iron Administration ◽  
Serum Ferritin Concentration ◽  
Low Serum

Unexplained Serum Ferritin Elevations in Primary Care Patients with Elevated Serum Ferritin Concentrations and High Normal Transferrin Saturations.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 3729-3729
Author(s):  
Onyinye C. Onyekwere ◽  
Tiffany N. Johnson ◽  
Margaret Fadojutimi-Akinsiku ◽  
Fitzroy Dawkins ◽  
Victor Gordeuk
Keyword(s):  
Primary Care ◽  
African Americans ◽  
Iron Overload ◽  
Serum Ferritin ◽  
Transferrin Saturation ◽  
Elevated Serum ◽  
Ferritin Concentration ◽  
Serum Ferritin Concentration ◽  
Primary Care Patients ◽  
Hfe Mutations

Abstract Non-HFE primary iron overload exists in African Americans and other ethnic groups, but the prevalence and spectrum of clinical manifestations are not known. In the HEIRS (Hereditary Hemochromatosis and Iron Overload Screening) Study, participants were considered for further evaluation if the serum ferritin concentration was elevated and the transferrin saturation was more than 45% for women or 50% for men. We hypothesized that these screening criteria would miss a substantial number of African Americans and members of other ethnic groups with increased iron stores. In the process of screening 21,231 predominantly African-American and Hispanic primary care patients at the Howard University field center of the HEIRS Study, we identified 161 non-HFE-C282Y homozygotes ≥ 25 years of age with serum ferritin concentrations above the 97.5 percentile for the population (&gt;700 ng/ml for men and &gt;500 ng/ml for women) but transferrin saturations in the upper part of the normal range (35–50% for men and 30–45% for women). Of the 123 participants we were able to contact, 68 (55%) participated in a clinical evaluation, including 64 African Americans, three Hispanics and one Asian American with a mean ± SD age of 57 ± 13 years. Thirty-eight (56%) were females, 6 (9%) were HFE H63D heterozygotes and 2 (3%) were C282Y heterozygotes. Seven patients (10%) had normal serum ferritin concentration on repeat testing while 42 (62%) had potential reasons for elevated serum ferritin concentration other than a primary increase in body iron including (sequentially) multiple blood transfusions (&gt;10 lifetime; n = 4), abnormal liver function tests (hepatitis C positive or AST &gt;60 IU/L and AST&gt;ALT; n = 17), hemoglobin &lt; 10 g/dL men or 9 g/dL women (n = 1), elevated C-reactive protein with transferrin saturation not elevated (n = 17), and excessive alcohol use (n = 3). Nineteen patients did not have these explanations for increased serum ferritin concentration and were considered to have a possible primary iron-loading process (see Table). One of the patients with unexplained elevated serum ferritin concentration (an African American) had a diagnostic liver biopsy showing 2-3+ hepatocellular iron and heavy iron deposition in Kupffer cells and is on phlebotomy therapy; the others have been advised to have diagnostic liver biopsy or quantitative phlebotomy. We conclude that there are substantial numbers of African Americans with elevated serum ferritin concentration and normal transferrin saturation who have transfusional iron overload or a probable primary increase in body iron stores. Characteristics of 19 Patients with Unexplained Serum Ferritin Elevations No. (%) of Women 8 (42) Age inyears (mean ± SD) 63 ± 14 Race (African American:Hispanic:Asian) 16:2:1 Hemoglobin in g.dL (mean ± SD) Men 13.8 ±1.5 Hemoglobin in g.dL (mean ± SD) Women 12.9 ± 0.8 HFE mutations in no. (%) C282Y heterozygotes 0 (0) HFE mutations in no. (%) H63D heterozygotes 2 (11) Ferritin category in no. (%) &lt; 500 ng/ml 7 (37) Ferritin category in no. (%) 500–1000 ng/ml 9(57) Ferritin category in no. (%) 1000 ng/ml&gt; 3 (16)

Subpopulations with Iron Deficiency, Liver Disease, or HFE Mutations Revealed by Statistical Mixture Modeling of Transferrin Saturation and Serum Ferritin Concentration in Asians, African Americans, Hispanics, and Whites.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 2672-2672
Author(s):  
Christine E. McLaren ◽  
Victor R. Gordeuk ◽  
Wen-Pin Chen ◽  
James C. Barton ◽  
Ronald T. Acton ◽  
...  
Keyword(s):  
At Risk ◽  
Liver Disease ◽  
African Americans ◽  
Iron Deficiency ◽  
Serum Ferritin ◽  
Transferrin Saturation ◽  
Mixture Modeling ◽  
Ferritin Concentration ◽  
Serum Ferritin Concentration ◽  
Hfe Mutations

Abstract In previous investigations, we modeled the distribution of transferrin saturation (TS) in Caucasians and demonstrated a strong association between HFE genotype and TS subpopulations. Extending this approach, we now have analyzed joint population distributions of TS and serum ferritin concentration (SF) measured in the multi-ethnic Hemochromatosis and Iron Overload Screening (HEIRS) Study and examined the association of these distributions with the presence of HFE C282Y and H63D mutations, self-reported liver disease, and iron deficiency (defined as SF &lt;15 μg/L). Based on separate models for each race/ethnicity by gender, four components with successively increasing age-adjusted means for TS and SF were identified in data from 26,832 African Americans, 12,620 Asians, 12,264 Hispanics, and 43,254 Whites. Fig. 1 illustrates age-adjusted values from 16,662 White men. Superimposed 95% confidence ellipses reflect component probability densities and show separation of the 1st and 4th components that had the lowest and highest means for TS and SF, respectively. Table 1 presents the range of estimates from individual models and indicates that the 2nd (largest) component had TS means of 22–26% for women (29–30% for men) and SF means of 43–82 μg/L for women (165–242 μg/L for men). The 3rd and 4th components had progressively smaller proportions and higher mean values of TS and SF, while the 1st component in each model had mean TS &lt;16% for women (&lt;20% for men), and mean SF &lt;28 μg/L for women (&lt;47 μg/L for men). Compared to the 2nd component: adjusted odds of iron deficiency were significantly higher in the 1st component (15–48 for women, 61–3530 for men); adjusted odds of self-reported liver disease were significantly higher in the 3rd and 4th components for African-American women and all men; and adjusted odds of any HFE mutation were increased in the 3rd component (1.4–1.8 for women, 1.2–1.9 for men) and in the 4th component for Hispanic and White women (1.5, 5.2, respectively) and men (2.8, 4.7, respectively). Joint mixture modeling identifies one component with lower mean SF and TS at risk for iron deficiency and two components with higher mean SF and TS at risk for liver disorders and HFE mutations. This approach permits characterization of the aggregate effects of hereditary or acquired factors that influence these serum iron measures in populations, and complements and enhances genetic and phenotypic testing for assessment of disease characteristics. Table 1 Range of estimates from models.

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