The Paediatric Iron Deficiency Assessment with Reticulocyte Haemoglobin Equivalent (Ret-He) in Comparison with Biochemical Markers of Serum Ferritin and Transferrin Saturation

Diagnosis of iron deficiency anaemia (IDA) is a challenge as the conventional methods often diagnose the disease at the later stage. Haemoglobin content of reticulocytes is useful to identify IDA at earlier stage. The objective of this study was to evaluate reticulocyte-haemoglobin equivalent (Ret-He) in diagnosing IDA in children and to compare it with other conventional methods. This prospective study was conducted on 120 paediatric patients aged 12 years and below, who attended Hospital Sultanah Aminah Johor Bahru, Malaysia with haemoglobin <12 g/dL. Ret-He and serum iron, ferritin and transferrin saturation were measured. Using a cut-off point of 20% for transferrin saturation, 81 out of 120 subjects (67.5%) were found as iron deficient. Based on the diagnosis of IDA, cut-off value for Ret-He using the Receiver Operating Characteristics (ROC) curve analysis was found as 22.65 pg. Ret-He showed a good sensitivity and specificity of 77.8% and 66.7%, respectively. As compared with Ret-He, serum ferritin showed a sensitivity of only 18.9%. However, a good specificity of 100% suggest it is useful for ruling in the disease but not suitable for screening. Transferrin saturation showed a good sensitivity and specificity, but it is biologically variable and not cost effective as a screening tool. Correlation study showed serum iron and transferrin saturation have significant positive correlation with Ret-He (r=0.415 to 0.518). However, there was no correlation between Ret-He and serum ferritin (r=0.051, p=0.578). This study shows that Ret-He at a cut-off point of 22.65 pg has a better sensitivity and potentially be useful as a screening tool in the paediatric population.

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Serum iron and total iron-binding capacity compared with serum ferritin in assessment of iron deficiency.

Clinical Chemistry ◽

10.1093/clinchem/27.2.276 ◽

1981 ◽

Vol 27 (2) ◽

pp. 276-279 ◽

Cited By ~ 15

Author(s):

F Peter ◽

S Wang

Keyword(s):

Iron Deficiency ◽

Serum Ferritin ◽

Serum Iron ◽

Binding Capacity ◽

Transferrin Saturation ◽

Total Iron ◽

Iron Binding ◽

Total Iron Binding Capacity ◽

Iron Deficient ◽

Iron Binding Capacity

Abstract Ferritin values for 250 selected sera were compared with values for iron, total iron-binding capacity (TIBC), and transferrin saturation, to assess the potential of the ferritin assay for the detection of latent iron deficiency. The specimens were grouped (50 in each group) according to their values for iron and TIBC. In Group 1 (low iron, high TIBC) the saturation and ferritin values both indicated iron deficiency in all but one. In the 100 specimens of Groups 2 (normal iron, high TIBC) and 4 (normal iron, high normal TIBC), the saturation values revealed 16 iron-deficient cases, the ferritin test 55. For Groups 3 (low iron, normal TIBC) and 5 (low iron, low TIBC), the ferritin test revealed fewer cases of iron deficiency than did the saturation values (37 cases vs 51 cases, in the 100 specimens). Evidently the ferritin test detects iron deficiency in many cases for whom the serum iron and TIBC tests are not positively indicative. The correlation of serum ferritin with iron, TIBC, and transferrin saturation in the five groups was good only in the case of specimens for which the TIBC was normal; if it was abnormal the correlation was very poor.

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Correlation between vivax malaria infection and iron deficiency in children

Paediatrica Indonesiana ◽

10.14238/pi55.1.2015.44-9 ◽

2015 ◽

Vol 55 (1) ◽

pp. 44

Author(s):

Desmansyah Desmansyah ◽

Rini Purnamasari ◽

Theodorus Theodorus ◽

Sulaiman Waiman

Keyword(s):

Iron Deficiency ◽

Serum Ferritin ◽

Vivax Malaria ◽

Malaria Infection ◽

Serum Iron ◽

Iron Status ◽

Transferrin Saturation ◽

Hemoglobin Level ◽

Ferritin Concentration ◽

Iron Deficient

Background Iron deficiency is considered to be a major public health problem around the world due to its high prevalence as well as its effect on growth, development, and infection-resistance in children. In malaria-endemic areas, malaria infection is thought to contribute to the occurrence of iron deficiency, by means of hepcidin and hemolysis mechanisms. Objective To assess the prevalence of asymptomatic vivax malaria, compare hemoglobin levels and iron status parameters between vivax malaria-infected and uninfected children, assess the prevalence of iron deficiency, and evaluate a possible correlation between vivax malaria infection and iron deficiency. Methods This cross-sectional study was conducted from February to April 2013 at Sanana City of Sula Islands District, North Maluku. Six parameters were evaluated in 5-11-year-old children: malaria parasite infection, hemoglobin level, serum iron concentration, total iron-binding capacity (TIBC), serum transferrin saturation, and serum ferritin concentration. Results Among 296 children aged 5-11 years, 75 (25.3%) were infected with Plasmodium vivax. In infected children, hemoglobin, serum iron, transferrin saturation, TIBC and serum ferritin were significantly lower than in non-infected children (P<0.01). Using a serum ferritin cut-off of <15 μg/dL, 142 (48.0%) of the children were found to be iron deficient. There was a strong correlation between vivax malaria infection and iron deficiency (OR 3.573; 95%CI 2.03-6.29). ConclusionThe prevalence of asymptomatic vivax malaria infection was 25.3%. The hemoglobin level and iron status parameters in vivax malaria-infected subjects were significantly lower than in uninfected children. The prevalence of iron deficiency was 48.0% for all study subjects. Malaria vivax infection was correlated with iron deficiency in 5-11-year-old children at Sanana City.

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Regression Correction Equation to Adjust Serum Iron and Ferritin Concentrations Based on C-Reactive Protein and Albumin in Patients Receiving Primary and Secondary Care

Journal of Nutrition ◽

10.1093/jn/nxz008 ◽

2019 ◽

Vol 149 (5) ◽

pp. 877-883 ◽

Cited By ~ 3

Author(s):

Stephen T McSorley ◽

Alexander Tham ◽

Iain Jones ◽

Dinesh Talwar ◽

Donald C McMillan

Keyword(s):

Iron Deficiency ◽

Linear Regression ◽

Serum Ferritin ◽

Secondary Care ◽

Serum Iron ◽

C Reactive Protein ◽

Reactive Protein ◽

Iron Deficient ◽

Significant Difference ◽

Low Levels

ABSTRACT Background Systemic inflammation, even at low levels, can greatly interfere with measures of iron status, making diagnosis of iron deficiency difficult. The objective of the present study was to create linear regression correction equations to adjust serum ferritin and iron concentrations based on measurements of the acute-phase proteins C-reactive protein (CRP) and albumin. Methods Data from a cohort (1) of patients (n = 7226) in primary and secondary care who had serum ferritin, iron, CRP, and albumin measured at the same time point were examined. Linear regression coefficients were calculated for CRP and albumin with serum iron and ferritin as the outcome variables. Patients with ferritin <15 µg/L or serum iron <10 µmol/L were categorized as iron deficient. The equation was then applied to a cohort (2) of patients with colorectal cancer who had ferritin and iron measured preoperatively ( n = 356). Results In cohort 1 there was a significant difference in the proportions of patients with serum ferritin <15 µg/L and serum iron <10 µmol/L, respectively, when the unadjusted (7% and 55%), adjusted based on CRP alone (13% and 26%), adjusted based on albumin alone (11% and 37%), and adjusted based on both CRP and albumin (24% and 15%) values were compared (both P < 0.001). In cohort 2 there was a significant difference in the proportions of patients with serum ferritin <15 µg/L and serum iron <10 µmol/L, respectively, when the unadjusted (28% and 66%), adjusted based on CRP alone (39% and 57%), adjusted based on albumin alone (39% and 59%), and adjusted based on both CRP and albumin (46% and 44%) values were compared (P < 0.001 and P < 0.004). Conclusions In both cohorts the greatest increase in the proportion of patients meeting definitions of iron deficiency was found when adjustment was made for both CRP and albumin together. Even low levels of inflammation had a significant effect on serum iron and ferritin values.

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Evaluation of the iron status of a population

Blood ◽

10.1182/blood.v48.3.449.449 ◽

1976 ◽

Vol 48 (3) ◽

pp. 449-455 ◽

Cited By ~ 293

Author(s):

JD Cook ◽

CA Finch ◽

NJ Smith

Keyword(s):

Iron Deficiency ◽

Serum Ferritin ◽

Iron Status ◽

Transferrin Saturation ◽

Red Cell ◽

Adult Males ◽

Packed Red Blood Cells ◽

Iron Deficient ◽

Menstruating Women ◽

Prevalence Of Anemia

Abstract The iron status of a population of 1564 subjects living in the northwestern United States was evaluated by measurements of transferrin saturation, red cell protoporphyrin, and serum ferritin. The frequency distribution of these parameters showed no distinct separation between normal and iron-deficient subjects. When only one of these three parameters was abnormal (transferrin saturation below 15%, red cell protoporphyrin above 100 mug/ml packed red blood cells, serum ferritin below 12 ng/ml), the prevalence of anemia was only slightly greater (10.9%) than in the entire sample (8.3%). The prevalence of anemia was increased to 28% in individuals with two or more abnormal parameters, and to 63% when all three parameters were abnormal. As defined by the presence of at least two abnormal parameters, the prevalence of iron deficiency in various populations separated on the basis of age and sex ranged from 3% in adolescent and adult males to 20% in menstruating women. It is concluded that the accuracy of detecting iron deficiency in population surveys can be substantially improved by employing a battery of laboratory measurements of the iron status.

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The Role of α-Thalassemia and Iron Deficiency in the Difference between Hemoglobin Levels of African-Americans (AA) and Whites.

Blood ◽

10.1182/blood.v104.11.3706.3706 ◽

2004 ◽

Vol 104 (11) ◽

pp. 3706-3706

Author(s):

Ernest Beutler ◽

Carol West

Keyword(s):

Iron Deficiency ◽

Serum Ferritin ◽

Gene Frequency ◽

Ferritin Level ◽

Transferrin Saturation ◽

Hemoglobin Concentration ◽

Iron Deficient ◽

High Prevalence ◽

Hardy Weinberg Equilibrium ◽

The Difference

Abstract The fact that the average hemoglobin concentration (Hb) of AA is lower than that of whites has been documented extensively. Several investigations have shown that this difference of approximately 0.8 g/dL is due neither to iron deficiency nor to socioeconomic status. Its cause remains unknown. We compared the Hb of 1,493 AA and 31,029 white anonymized patients attending a Health Appraisal Clinic and confirmed the known difference in Hb, both for females and males (0.79 and 0.47 g/dL) respectively. The difference persisted when a subset of the subjects were paired by age and narrowed slightly in females when those with serum ferritin levels of <10 ng/ml or transferrin saturations of <16% were excluded (difference in females 0.59 g/dL; males 0.47). We determined the α-thalassemia −3.7 genotype of 298 AA. The gene frequency was found to be 0.17, and the distribution of genotypes fit the Hardy-Weinberg equilibrium. However, in a sample of 155 white subjects only one α-thalassemia allele was found (gene frequency=0.003). Among the AA subjects, the Hb and MCV values were lower in homozygotes (−a/−a) and heterozygotes (aa/−a) for α-thalassemia than in the aa/aa subjects. The table presents data for AA and white subjects after excluding all who did not have a documented serum ferritin level of >9 ng/ml and a transferrin saturation of >16%. Excluding subjects with sickle trait had no effect. Ethnic Group Genotype n Mean Hb SE Hb Mean MCV SE MCV −a/−a 3 11.87 0.418 72.23 2.32 F AA aa/−a 20 12.69 0.202 85.22 0.86 aa/aa 65 13.17 0.127 90.43 0.61 White 2917 13.60 0.016 90.85 0.07 −a/−a 2 13.85 0.550 83.05 1.65 M AA aa/−a 36 14.37 0.161 85.81 0.78 aa/aa 86 14.75 0.123 89.78 0.53 White 5335 15.09 0.013 90.35 0.06 As shown in the table, the average Hb of non-iron deficient AA females and males who had 4 normal α loci (aa/aa) was 0.43 and 0.34 g/dL lower respectively than those of whites, the difference being significant with p<0.01. We conclude that one cause of the lower Hb of AA compared to white subjects is the high prevalence of α-thalassemia in the AA population, but that it accounts for only about one-quarter of the difference after iron deficiency has been excluded. There are other, as yet undefined, causes that play a role. These may include the lower ATP (Biochem. Genet.1:25, 1967) and higher 2,3 BPG (Transfusion18:108, 1978) levels that have been documented in the red cells of AA subjects.

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High Prevalence of Iron Deficiency In Anemic and Non Anemic Patients with Various Types of Cancer

Blood ◽

10.1182/blood.v116.21.5145.5145 ◽

2010 ◽

Vol 116 (21) ◽

pp. 5145-5145

Author(s):

Heinz Ludwig ◽

Georg Endler ◽

Brigitte Klement ◽

Wolfgang Hüubl ◽

Tim Cushway

Keyword(s):

Iron Deficiency ◽

Serum Ferritin ◽

Multiple Testing ◽

Serum Iron ◽

Iron Supplementation ◽

Complete Blood Count ◽

Clinical Symptoms ◽

Iron Status ◽

Transferrin Saturation ◽

Patients With Cancer

Abstract Abstract 5145 Introduction and aims: Iron deficiency as a major component in the pathogenesis of anemia in cancer is not acknowledged by most oncologists, possibly except when arising from GI blood loss. Iron deficiency is associated with clinical symptoms such as cognitive impairment, fatigue, and reduced exercise performance. New iron formulations are available that allow rapid iron supplementation with single infusions. This treatment could ameliorate symptoms of iron deficiency and correct anemia. Here, we studied iron parameters and their correlation with erythropoiesis and inflammatory markers in a large unselected cohort of patients with cancer. In addition, we investigated the suitability of serum ferritin and transferrin saturation (TSAT) as parameter for assessment of the iron status. Patients and methods: Data from 1627 patients (median age: 66.4 years, range: 20–97 years) presenting sequentially at the Center for Oncology and Hematology, Wilhelminenspital, Vienna between October 01, 2009 and January 26, 2010, have retrospectively been analyzed. Patients were at different stages of their disease or may not have had an established diagnosis at the time of testing. In patients with multiple testing during this period only the first sample taken was included. TSAT (n=1516), serum ferritin (n=887), serum iron, CRP, and complete blood count, were determined by using standard techniques. Commonly used definitions for absolute iron deficiency (AID), [TSAT <20% and serum ferritin <30ng/ml, in case serum ferritin was not available TSAT <10%] and for functional iron deficiency (FID), [TSAT <20% and serum ferritin ≥30ng/ml, in case serum ferritin was not available TSAT between 10 and 20%] have been applied. Fisher's exact test was used for comparison of frequencies and Pearson's product moment correlation coefficient for evaluation of correlation. Results: Table 1 shows the distribution of TSAT and serum ferritin categories in 1627 patients with cancer. AID was found in 116 patients (7.7%) of the 1516 patients for whom TSAT was available. Eighty-three (72%) of the AID patients presented with anemia (defined by hemoglobin <12g/dl). AID was most common in patients with colorectal and pancreatic cancer (12% and 11%, respectively), and not present in patients with testicular and prostate cancer (p=0.013). FID was diagnosed in 530 patients (35%) and 222 (42%) of them were found to be also anemic. Multivariate analysis revealed a statistically significant correlation between TSAT and serum ferritin (R=0.286, p<0.001), serum iron (R=0.874, p<0.001), hemoglobin (R=0.201, p<0.001) and CRP (R=-0.205, p<0.001) (figure 1). Serum ferritin, in contrast, did not correlate with serum iron (R=0.051, p=0.132), but correlated with hemoglobin (R=-0.259, p<0.001), TSAT (R=0.286, p<0.001), and CRP (R=0.396, p<0.001). Conclusion: AID (7.7%) and even more so FID (35%) are frequent co-morbidities in patients with various types of cancer. Seventy-two percent of patients with AID and 42% with FID presented with overt anemia. TSAT correlated closely with serum iron and hemoglobin levels and seems to be the preferred parameter for assessment of iron status in patients with chronic diseases often complicated by increased inflammation. Serum ferritin was found to be an inadequate parameter for assessment and monitoring of iron status. As iron deficiency has been linked with various symptoms, the question arises whether iron supplementation would benefit patients with FID without overt anemia. Future studies should evaluate the role of novel intravenous iron preparations in ameliorating the symptoms of iron deficiency with or without anemia. Disclosures: Klement: Vifor Pharma Ltd: Employment. Cushway:Vifor Pharma Ltd.: Employment.

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Prevalence of Iron, Vitamin B12 deficiency and inflammatory anaemia in treatment naive individual consecutive cancer patients: A cross sectional study.

10.1101/2020.07.29.20164426 ◽

2020 ◽

Author(s):

Avinash Pandey ◽

Shivkant Singh ◽

Raj Aryan ◽

Krishna Murari

Keyword(s):

Iron Deficiency ◽

Vitamin B12 ◽

Cancer Patients ◽

Serum Ferritin ◽

Transferrin Saturation ◽

Vitamin B12 Deficiency ◽

Cross Sectional ◽

Iron Deficient ◽

Treatment Naïve ◽

B12 Deficiency

Background: In treatment naive Indian cancer patients, prevalence of iron, B12 deficiency and inflammatory anaemia in poorly known. Aims and Objectives : To evaluate prevalence of anaemia and iron, B12 deficiency along with inflammation in treatment naive individual consecutive cancer patients. Material and Methods: All patients registered from 1st July 2019 till 31st December 2019 in Medical Oncology Outpatient Department were offered to undergo Iron profile, Serum B12 levels and Serum ferritin along with routine haematological investigations. Anaemia was defined as Haemoglobin < 11gm/dL. Transferrin saturation <20%, Serum Ferritin >300 microgram/litre and Vitamin B12 level <200 picogram/millilitre were 'cut-offs' used to define iron deficiency, inflammation and Vitamin B12 deficiency respectively. Data was analysed using descriptive statistics, frequency distribution, crosstabs and Bar Diagram in SPSS version 17.0. Pearsons Chi square test and Odds ratio was used to measure the strength of association with variables. Results: 311/441 (70.5%) were found eligible. Median age was 52 + 15.9 (Range 18-84 ) years with 144/331(46%) females. The prevalence of anaemia was 61% + 2.7 (95% CI 55-66%). Mean Haemoglobin was 9.86 + 2.08 (range 3-16) gram/decilitre. 21/311(7%) had severe anaemia (Haemoglobin < 6.9 gm/dl). 135/311 (71%), 61/189 (32%) and 89/189 (47%) anaemic patients had iron deficiency, inflammation and B12 deficiency respectively. More than 70% of Gastrointestinal (50/69), Gynaecological(17/24) and Lung Cancer(18/22) patients had underling Iron deficiency. Conclusion: Two-third of cancer patients are iron deficient. B12 deficiency and inflammation are present in half and one-third patients respectively.

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

Blood ◽

10.1182/blood.v126.23.3354.3354 ◽

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.

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Measuring Reticulocyte Hemoglobin Content As a Marker for Iron Deficiency and Response to Therapy Represents a Paradigm Shift in Care

Blood ◽

10.1182/blood-2020-134693 ◽

2020 ◽

Vol 136 (Supplement 1) ◽

pp. 42-43

Author(s):

Michael Auerbach ◽

Carlo Brugnara ◽

Steve Staffa

Keyword(s):

Iron Deficiency ◽

Serum Ferritin ◽

Biochemical Markers ◽

Roc Analysis ◽

Transferrin Saturation ◽

Iron Administration ◽

Iron Deficient ◽

Ferritin Iron ◽

Iv Iron ◽

Iron Replacement

It is estimated anemia affects over 30% of the world's population, with iron deficiency (ID) the overwhelmingly most common cause. Whether absolute due to blood loss and/or iron sequestration to underlying morbidity, the need for repletion especially in females, is a formidable medical issue. The diagnosis of iron deficient erythropoiesis has been traditionally based on the biochemical parameters ferritin and percent transferrin saturation (TSAT), mean cell volume and hemoglobin (Hb) concentration. In recent years, reticulocyte Hb content has emerged as a parameter helpful in identifying iron deficient erythropoiesis and informing a need, or lack thereof, for replacement. 556 consecutive, non-selected patients referred for diagnosis and/or treatment of anemia were included in this diagnostic study to compare the performance of reticulocyte hemoglobin equivalent (RET-He) versus traditional biochemical markers for diagnosis and treatment of IDA. CBC, serum ferritin, iron and TSAT were performed as clinically indicated. RET-He was measured with a Sysmex XN-450 analyzer on the residual CBC sample. 556 patients were studied at baseline and 150 were subsequently treated with intravenous (IV) iron. 240/556 were seen at follow-up, with 57 treated and 183 not treated with IV iron. At baseline, ret-He, positively correlated with Hb (Spearman correlation (rho)=0.365, P < 0.001), MCV (rho=0.576, P < 0.001), MCH (rho=0.777, P < 0.001), serum iron (rho=0.526, P < 0.001) and TSAT (rho=0.492, P < 0.001). Serum iron, and TSAT (but not serum ferritin or MCV, or absolute reticulocyte count) positively correlated with Hb concentrations. Based on either a serum ferritin <30 ng/ml and/or a TSAT< 20%, 241/556 (43.4%) patients were diagnosed as iron deficient. Anemia was present in 64/241 of the iron deficient patients (26.6%). Despite the limitations of the biochemical markers outlined above, we performed ROC analysis assessing the value of RET-He in identifying iron deficiency as defined by serum ferritin <30 ng/mL or transferrin saturation <20%. ROC analysis demonstrates a reasonable performance for RET-He (AUC= 0.733, 95% CI: 0.692, 0.775), with a cut-off value of <30.7 pg yielding 68.2% sensitivity and 69.7% specificity. Using both Hb and RET-He in a multivariable ROC analysis does not provide an improved AUC, as compared to just using RET-He (AUC=0.605 vs.0.733). IV iron administration was associated with significant increases in Hb, MCV, MCH, RET-He, serum ferritin, iron and TSAT, whereas in the no-IV iron cohort, there was a small reduction in RET-He and small increases in MCV and MCH, with no significant variations in Hb and in the other parameters. Serum ferritin was below 30 ng/mL in 18/57 (32%) of the patients requiring IV iron and in 19/183 (10.4%) of those not requiring iron at visit 1. These values changed to 4/57 (7%) (P=0.002) and 23/183 (13%) (P=0.623) at visit 2, respectively. Regression analysis for Hb response following IV iron showed that baseline RET-He values are predictive of Hb response, with every unitary increase in RET-He corresponding to a blunting of the Hb change by -0.19 g/dl (95% CI: -0.27, -0.11; P < 0.001). Changes in RE-He associated with IV iron administration are also predictive of the Hb response, with every additional unit increase in RET-He corresponding to a 0.21 g/dL increase in Hb (95% CI: 0.13, 0.28; P < 0.009). ROC analysis for the capability to predict Hb response among the 57 patients receiving IV iron shows that a value of baseline RET-He < 28.5 pg together with a baseline Hb value < 10.3 g/dL provide the highest Youden's index for predicting Hb response > 1.0 g/dl, with sensitivity of 84% and specificity of 78%. The Figure presents data for the 21/57 patients who had RET-He < 28.5 pg and Hb < 10.3 g/dL vs the 36/57 who did not. The present data show that an abnormally low ret-He value (< 28.5 pg) identifies patients who will respond to iron replacement, obviating delays to obtain standard iron parameters. Baseline and changes in ret-He also associate with Hb response. Given the enormous prevalence of ID in the general population the use of the ret-He, which is available with the CBC on the autoanalyzer, informs need for iron replacement, or lack thereof, represents an increase in convenience for patient and physician, decreases costs, streamlines care and represents an improvement in the treatment paradigm of one of the commonest maladies on the planet. Figure 1 Disclosures Auerbach: AMAG: Research Funding; Sysmex: Research Funding. Brugnara:American Journal of Hematology: Other; Sysmex America Inc.: Consultancy.

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Optimization of Epoetin Therapy with Intravenous Iron Therapy in Hemodialysis Patients

Journal of the American Society of Nephrology ◽

10.1681/asn.v113530 ◽

2000 ◽

Vol 11 (3) ◽

pp. 530-538

Author(s):

ANATOLE BESARAB ◽

NEETA AMIN ◽

MUHAMMAD AHSAN ◽

SUSAN E. VOGEL ◽

GARY ZAZUWA ◽

...

Keyword(s):

Iron Deficiency ◽

Serum Ferritin ◽

Transferrin Saturation ◽

Intravenous Iron ◽

Hemodialysis Patients ◽

Chronic Hemodialysis ◽

Control Group ◽

Zinc Protoporphyrin ◽

Study Group ◽

Iron Deficient

Abstract. Iron deficiency limits the efficacy of recombinant human erythropoietin (rhEPO) therapy in end-stage renal disease (ESRD) patients. Functional iron deficiency occurs with serum ferritin >500 ng/ml and/or transferrin saturation (TSAT) of 20 to 30%. This study examines the effects of a maintenance intravenous iron dextran (ivID) protocol that increased TSAT in ESRD hemodialysis patients from conventional levels of 20 to 30% (control group) to those of 30 to 50% (study group) for a period of 6 mo. Forty-two patients receiving chronic hemodialysis completed a 16- to 20-wk run-in period, during which maintenance ivID and rhEPO were administered in amounts to achieve average TSAT of 20 to 30% and baseline levels of hemoglobin of 9.5 to 12.0 g/dl. After the run-in period, 19 patients randomized to the control group received ivID doses of 25 to 150 mg/wk for 6 mo. Twenty-three patients randomized to the study group received four to six loading doses of ivID, 100 mg each, over a 2-wk period to achieve a TSAT >30% followed by 25 to 150 mg weekly to maintain TSAT between 30 and 50% for 6 mo. Both regimens were effective in maintaining targeted hemoglobin levels. Fifteen patients in the control group and 17 patients in the study group finished the study in which the primary outcome parameter by intention to treat analysis was the rhEPO dose needed to maintain prestudy hemoglobin levels. Maintenance ivID requirements in the study group increased from 176 to 501 mg/mo and were associated with a progressive increase in serum ferritin to 658 ng/ml. Epoetin dose requirements for the study group decreased by the third month and remained 40% lower than for the control group, resulting in an overall cost savings in managing the anemia. Secondary indicators of iron-deficient erythropoiesis were also assessed. Zinc protoporphyrin did not change in either group. Reticulocyte hemoglobin content increased only in the study group from 28.5 to 30.1 pg. It is concluded that maintenance of TSAT between 30 and 50% reduces rhEPO requirements significantly over a 6-mo period.

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