scholarly journals Incidence of Iron Deficiency and the Role of Intravenous Iron Use in Perioperative Periods

Medicina ◽  
2020 ◽  
Vol 56 (10) ◽  
pp. 528
Author(s):  
Mirela Țigliș ◽  
Tiberiu Paul Neagu ◽  
Andrei Niculae ◽  
Ioan Lascăr ◽  
Ioana Marina Grințescu
Keyword(s):  
Bone Marrow ◽  
Iron Deficiency ◽  
Case Reports ◽  
Transferrin Saturation ◽  
Intravenous Iron ◽  
Surgical Patients ◽  
Systemic Review ◽  
Mean Corpuscular Hemoglobin ◽  
Transfusion Rate ◽  
Parenteral Iron

Iron deficiency is a major problem in worldwide populations, being more alarming in surgical patients. In the presence of absolute iron deficiency (depletion of body iron), functional iron deficiency (during intense bone marrow stimulation by endogenous or exogenous factors), or iron sequestration (acute or chronic inflammatory conditions), iron-restricted erythropoiesis can develop. This systemic review was conducted to draw attention to the delicate problem of perioperative anemia, and to provide solutions to optimize the management of anemic surgical patients. Systemic reviews and meta-analyses, clinical studies and trials, case reports and international guidelines were studied, from a database of 50 articles. Bone marrow biopsy, serum ferritin levels, transferrin saturation, the mean corpuscular volume, and mean corpuscular hemoglobin concentration were used in the diagnosis of iron deficiency. There are various intravenous iron formulations, with different pharmacological profiles used for restoring iron. In surgical patients, anemia is an independent risk factor for morbidity and mortality. Therefore, anemia correction should be rapid, with parenteral iron formulations—the oral ones—being inefficient. Various studies showed the safety and efficacy of parenteral iron formulations in correcting hemoglobin levels and decreasing the blood transfusion rate, the overall mortality, the postoperative infections incidence, hospitalization days, and the general costs.

scholarly journals Hepcidin-Mediated Ferroportin Control in the Bone Marrow Is Dispensable

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 3531-3531
Author(s):  
Katja Muedder ◽  
Bonadonna Michael ◽  
Bruno Galy ◽  
Martina U. Muckenthaler ◽  
Sandro Altamura
Keyword(s):  
Bone Marrow ◽  
Iron Deficiency ◽  
Iron Content ◽  
Bone Marrow Cells ◽  
Transferrin Saturation ◽  
Surface Expression ◽  
Mean Corpuscular Hemoglobin ◽  
Erythroid Cells ◽  
Hematopoietic Stem ◽  
Marrow Cells

25 mg of iron are required every day to sustain hematopoiesis in the bone marrow. Most iron is consumed by erythroid cells that take up transferrin-bound iron to satisfy their demand for hemoglobin biogenesis. Unexpectedly, erythroblasts express high levels of the iron exporter Ferroportin (Fpn). Fpn surface expression and activity is controlled by Hepcidin, a small liver peptide hormone, produced in response to elevated systemic and tissue iron availability. Resistance of ferroportin to hepcidin binding is caused by a gain of function mutation in the FpnC326S residue, which is the reason for iron overload in patients with Hereditary Hemochromatosis type 4. Some years ago we generated the corresponding mouse model hallmarked by this constitutively active iron exporter. We now applied bone marrow transplantation to investigate the role of the hepcidin/ferroportin regulatory system in cell types of the bone marrow (BM-FpnC326S). CD45.1 host mice were irradiated twice with 500 cGy 4h apart and injected with 2 million of BM cells obtained from C57BL/6N mice (control) or from C57BL/6N congenic constitutive FpnC326S animals. Mice were analyzed three months after transplantation, whereby only animals with an engraftment higher than 95% were included for further analyses. Analysis of the erythroid hematological parameters revealed mild macrocytosis in the presence of unaltered red blood cell count (RBC), hematocrit (HCT), hemoglobin (Hb) and mean corpuscular hemoglobin (MCH) values. Serum iron content, transferrin saturation and serum hepcidin levels remained unchanged, despite a strong decrease in splenic iron levels within the red pulp, where reticuloendothelial macrophages are located. The latter phenotype is consistent with high ferroportin surface expression in macrophages derived from FpnC326S monocytes that causes increased iron export and cellular iron deficiency. Cytokine production (IL1β, TNFα and IL6) in the spleen was unchanged suggesting that iron deficiency in splenic macrophages did not cause inflammation. In contrast to the spleen iron content was not changed in other organs analyzed, including the liver, suggesting that de novo monocyte infiltration is not a major feature in these organs. Interestingly, histological analysis of the femurs revealed a marked decrease in bone marrow iron content; we were unable to detect a single iron-stained cell in the bone marrow of BM-FpnC326S mice, contrasting results from control mice. To investigate whether iron deficiency in bone marrow cells alters numbers of immune cells, we performed a detailed characterization by FACS. Unexpectedly, iron deficiency in the bone marrow did not cause changes in total bone marrow cellularity, total numbers of Ter119+ erythroid cells and the percentage of different erythroblast subpopulations, the number of hematopoietic stem cells (HSC) and of common lymphoid (CLP), myeloid (CMP) and megakaryocyte/erythroid (MEP) progenitors. Taken together, our data clearly demonstrate that at steady state, the hepcidin/ferroportin regulatory circuitry in the bone marrow is dispensable and that iron deficiency in bone marrow cells is not altering the normal hematopoietic process. Future studies will have to extend the analysis to stress conditions. Disclosures Muckenthaler: Novartis: Research Funding; Silence Therapeutics: Consultancy.

scholarly journals Monitoring of iron status in patients with heart failure

2019 ◽  
Vol 21 (Supplement_M) ◽  
pp. M32-M35 ◽  
Author(s):  
Ewa A Jankowska ◽  
Michał Tkaczyszyn ◽  
Marcin Drozd ◽  
Piotr Ponikowski
Keyword(s):  
Heart Failure ◽  
Iron Deficiency ◽  
Serum Ferritin Level ◽  
Iron Status ◽  
Ferritin Level ◽  
Transferrin Saturation ◽  
Intravenous Iron ◽  
Accurate Method ◽  
Separate Entity ◽  
Patients With Heart Failure

Abstract The 2016 ESC/HFA heart failure (HF) guidelines emphasize the importance of identifying and treating iron deficiency (ID) in patients with HF. Iron deficiency can occur in half or more of HF sufferers, depending on age and the phase of the disease. Iron deficiency can be a cause of anaemia, but it is also common even without anaemia, meaning that ID is a separate entity, which should be screened for within the HF population. Although assessment of iron stores in bone marrow samples is the most accurate method to investigate iron status, it is not practical in most HF patients. Levels of circulating iron biomarkers are an easily available alternative; especially, ferritin and transferrin saturation (Tsat). In patients with HF serum ferritin level <100 µg/L (regardless of Tsat value) or between 100 and 299 µg/L with Tsat <20% are considered as recommended criteria for the diagnosis of ID, criteria which have been used in the clinical trials in HF that have led to a recommendation to treat ID with intravenous iron. We discuss the optimal measures of iron biomarkers in patients with HF in order to screen and monitor iron status and introduce some novel ways to assess iron status.

scholarly journals Inherited microcytic anemias

Hematology ◽  
2020 ◽  
Vol 2020 (1) ◽  
pp. 465-470
Author(s):  
Maria Domenica Cappellini ◽  
Roberta Russo ◽  
Immacolata Andolfo ◽  
Achille Iolascon
Keyword(s):  
Iron Deficiency ◽  
Blood Cell ◽  
Iron Metabolism ◽  
Red Blood Cell ◽  
Iron Status ◽  
Transferrin Saturation ◽  
Microcytic Anemia ◽  
Deficiency Anemia ◽  
Mean Corpuscular Hemoglobin ◽  
Distribution Width

Abstract Inherited microcytic anemias can be broadly classified into 3 subgroups: (1) defects in globin chains (hemoglobinopathies or thalassemias), (2) defects in heme synthesis, and (3) defects in iron availability or iron acquisition by the erythroid precursors. These conditions are characterized by a decreased availability of hemoglobin (Hb) components (globins, iron, and heme) that in turn causes a reduced Hb content in red cell precursors with subsequent delayed erythroid differentiation. Iron metabolism alterations remain central to the diagnosis of microcytic anemia, and, in general, the iron status has to be evaluated in cases of microcytosis. Besides the very common microcytic anemia due to acquired iron deficiency, a range of hereditary abnormalities that result in actual or functional iron deficiency are now being recognized. Atransferrinemia, DMT1 deficiency, ferroportin disease, and iron-refractory iron deficiency anemia are hereditary disorders due to iron metabolism abnormalities, some of which are associated with iron overload. Because causes of microcytosis other than iron deficiency should be considered, it is important to evaluate several other red blood cell and iron parameters in patients with a reduced mean corpuscular volume (MCV), including mean corpuscular hemoglobin, red blood cell distribution width, reticulocyte hemoglobin content, serum iron and serum ferritin levels, total iron-binding capacity, transferrin saturation, hemoglobin electrophoresis, and sometimes reticulocyte count. From the epidemiological perspective, hemoglobinopathies/thalassemias are the most common forms of hereditary microcytic anemia, ranging from inconsequential changes in MCV to severe anemia syndromes.

Hematologic Features of Iron Deficiency Anemia in Llamas

1992 ◽  
Vol 29 (5) ◽  
pp. 400-404 ◽  
Author(s):  
D. E. Morin ◽  
F. B. Garry ◽  
M. G. Weiser ◽  
M. J. Fettman ◽  
L. W. Johnson
Keyword(s):  
Iron Deficiency ◽  
Cell Volume ◽  
Iron Deficiency Anemia ◽  
Hemoglobin Concentration ◽  
Iron Therapy ◽  
Deficiency Anemia ◽  
Mean Corpuscular Hemoglobin ◽  
Volume Distribution ◽  
Mean Cell Volume ◽  
Parenteral Iron

Iron deficiency anemia was identified and characterized in three 14 to 29-month-old male llamas (llama Nos. 1–3) from separate herds in Colorado. The identification of iron deficiency anemia was based on hypoferremia (serum iron = 20–60 μg/dl), erythrocytic features, and hematologic response to iron therapy. The anemia was moderate and nonregenerative and characterized by erythrocyte hypochromia, microcytosis (mean cell volume = 15–18 fl), and decreased mean corpuscular hemoglobin concentration (36.0–41.0 g/dl). Morphologic features unique to llamas with iron deficiency anemia included irregular distribution of hypochromia within erythrocytes and increased folded cells and dacryocytes. The cause of iron deficiency was not determined. The llamas were treated with various doses and schedules of parenteral iron dextran. Two of the llamas were monitored for up to 14 months after the start of iron therapy and experienced increases in hematocrit and mean cell volume values. In one llama, progressive replacement of microcytic cells with normal cells was visualized on sequential erythrocyte volume distribution histograms following iron therapy.

scholarly journals Optimization of Epoetin Therapy with Intravenous Iron Therapy in Hemodialysis Patients

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.

Erythrocyte Volume Distribution Analysis and Hematologic Changes in Dogs with Iron Deficiency Anemia

1983 ◽  
Vol 20 (2) ◽  
pp. 230-241 ◽  
Author(s):  
G. Weiser ◽  
M. O'Grady
Keyword(s):  
Iron Deficiency ◽  
Iron Deficiency Anemia ◽  
Binding Capacity ◽  
Transferrin Saturation ◽  
Blood Film ◽  
Deficiency Anemia ◽  
Mean Corpuscular Hemoglobin ◽  
Volume Distribution ◽  
Distribution Analysis ◽  
Erythrocyte Volume

Hematologic features were characterized in 12 dogs with iron deficiency anemia attributable to chronic external blood loss. Consistent abnormalities in hemograms included moderate to marked reticulocytosis, decreased mean corpuscular volume, and decreased mean corpuscular hemoglobin concentration. Hypoproteinemia occurred in only four of 12 dogs. Consistent blood film findings included hypochromic cells, leptocytosis, and erythrocyte fragmentation. These dogs had significantly decreased serum iron values (p < 0.001) and percent transferrin saturation values (p < 0.001) compared with 33 clinically healthy adult dogs. The total iron binding capacity values of these dogs were not significantly different (p > 0.5) than those of the healthy dogs. Using erythrocyte volume distribution curves, the percentages of microcytic cells (≤ 45 fl) were determined to range from 20% to 82%. Sequential changes in erythrocyte subpopulations were evaluated in four dogs which received iron therapy. The hematologic response consisted of fairly rapid restoration of packed cell volume by production of normocytes followed by a more gradual replacement of residual microcytes by new normocytes.

A Novel Parameter for the Diagnosis of Iron Deficiency: The Transferrin/Albumin Ratio.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 3731-3731
Author(s):  
Laurence Pieroni ◽  
Claude Jardel ◽  
Helene Merle-Beral ◽  
Zahia Azgui ◽  
Sylvie Baudet ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Chronic Disease ◽  
Iron Deficiency ◽  
Iron Status ◽  
Mean Corpuscular Hemoglobin ◽  
Operating Characteristics ◽  
Iron Depletion ◽  
Ferritin Concentration ◽  
Albumin Ratio ◽  
Iron Stores

Abstract Iron deficiency (ID) is generally easily diagnosed by a serum ferritin concentration less than 12 μg/L. However, in patients with concomitant pathologies, sensitivity of ferritin for diagnosing ID is low, since inflammation or liver disease can lead to normal or increased ferritin values, even when iron deficiency. In this study, we propose a new marker for diagnosing ID in patients with chronic disease: the Transferrin/Albumin ratio (Tf/A ratio). Indeed, the synthesis and the elimination of albumin and transferrin are regulated by similar processes, excepted in ID. In the latter, the synthesis of transferrin is stimulated, whereas that of albumin is not. Therefore, the Tranferrin/Albumin ratio increases in case of ID, even when transferrin values are within the normal range. To determine the accuracy of this novel parameter, we studied 75 patients with chronic disease who were submitted to bone marrow aspirates and iron staining. Iron stores depletion was defined by less than 10% sideroblasts, without extra-cellular iron nor siderocytes. Blood samples were routinely undertaken at the time of the medullar sampling for determination of hematological and biochemical parameters. Iron status including ferritin, Tranferrin Saturation (TfSat), soluble Transferrin Receptor (sTfR), sTfR/log ferritin and Tf/A ratio, was determined. The diagnostic accuracy of the Tf/A ratio was compared to previously described parameters of iron status that we cited above. Receiver Operating Characteristics (ROC) curves were built to determine the best cut-off values for the prediction of iron deficiency. According to the Perls’ reaction, 25 of the 75 patients (33%) had depleted iron stores and 50 had normal or increased iron stores. Sixteen iron-depleted patients (67%) had anemia. Mann and Whitney U test showed that parameters significantly associated with ID were: Tf, Tf/A ratio, ferritin, TfSat, sTfR, sTfR/log ferritin, mean corpuscular volume, mean corpuscular hemoglobin, red blood cell and reticulocyte counts. In a multivariate analysis, the only significant, independent predictor of iron depletion was the Tf/A ratio (r = 0.637, p < 0.005). The sensitivity/specificity of Tf/A ratio at a cut-off point of 6.4% as given by ROC curve were 80%/88%. In conclusion, the Tf/A ratio is useful in the detection of iron depletion in patients with chronic disease and could dispense with bone marrow aspirate and Perls’ reaction in more than 80% of cases.

scholarly journals KEKURANGAN ZAT BESI DI PEREMPUAN HAMIL MENGGUNAKAN HEMOGLOBIN RETIKULOSIT (RET-HE)

2016 ◽  
Vol 19 (3) ◽  
pp. 156
Author(s):  
Petriana Primiastanti ◽  
Ninik Sukartini
Keyword(s):  
Bone Marrow ◽  
Iron Deficiency ◽  
Pregnant Women ◽  
Likelihood Ratio ◽  
Sensitivity And Specificity ◽  
Predictive Value ◽  
Transferrin Saturation ◽  
Stage I ◽  
Stage Ii ◽  
Bone Marrow Iron

Iron deficiency is the most common nutrional deficiency in the world, mostly in developing and industrial countries. Population with highest risk of iron deficiency generally are reproductive-age women. In Indonesia, the prevalence of iron deficiency anemia in pregnant women is about 50.5%. Anemia due to iron deficiency in pregnancy can affect both mother as well as the foetus. In order to prevent permanent systemic complication, it is important to do early detection before iron deficiency anaemia developes. In the early phase of iron deficiency prior to anaemia, additional tests of ferritin, serum iron and saturation index are needed besides the complete blood count. A new parameter named reticulocyte hemoglobin equivalent (RET-He) has been developed to detect the level of hemoglobin in an immature erythrocyte or reticulocyte. Reticulocytes will be present in the peripheral circulation for only 24−48 hours, so the RET-He will give more appropriate information about the condition of bone marrow iron. When the bone marrow iron is depleted, the RET-He will show a decrease. In several hematology analyzers, for example Advia 2120 and Sysmex XE 2100, this parameter can be tested together with CBC, so no additional blood sample is needed. The aim of this study is to know iron deficiency in healthy first and second trimester pregnant women by screening using RET-He and compare the result to other parameters that are now available, such as: hemoglobin, ferritin, transferrin saturation. Those parameters can develop RET-He cut-off with optimal sensitivity and specificity. The study comprised 100 healthy pregnant women from I and II trimester who did not develop anemia yet during their last pregnancy. The subjects were divided into three (3) groups based on ferritin and transferrin saturation: 67 women (67%) without iron deficiency, 17 women (17%) with iron deficiency stage I, and 16 women (16%) with iron deficiency stage II. Hemoglobin, RET-He, and transferrin saturation showed a mean±SD of 12.35±1.02 g/dL, 33.60±1.88 pg and 28.63±1.07%, respectively. Median ferritin (min-max) was 40.10 (6.24–191.30)ng/mL. By using receiver operating curve (ROC) in this study RET-He point was found at 33.65 pg as an optimal cut-off point to differentiate iron deficiency with sensitivity and specificity of 67% and 64.18% respectively. From cross tabs table of RET-He with ferritin as the gold standard and 33.65 pg as the cut-off point results were 47.8% positive predictive value (PPV), 79.6% negative predictive value (NPV), positive likelihood ratio (LR) 1.86 and negative likelihood ratio (LR) 0.52. In this study, significant differences between non iron deficiency and the iron deficiency stage II groups and between iron deficiency stage I and iron deficiency stage II groups were found. There was no difference between the non iron deficiency and iron deficiency stage I groups.

scholarly journals Parenteral Iron Sucrose Therapy for Moderate and Severe Iron-Deficiency Anemia in Pregnancy

2016 ◽  
Vol 22 (3) ◽  
pp. 125
Author(s):  
Sertac Esin ◽  
Bülent Yırcı ◽  
Tuğba Zengin ◽  
Serdar Yalvaç ◽  
Ömer Kandemir
Keyword(s):  
Iron Deficiency ◽  
Hypersensitivity Reaction ◽  
Iron Deficiency Anemia ◽  
Intravenous Iron ◽  
Pregnant Patient ◽  
Iron Sucrose ◽  
Deficiency Anemia ◽  
Parenteral Iron ◽  
The Mean ◽  
The Difference

<p><strong>Objective:</strong> Parenteral iron therapy for iron deficiency anemia is gaining popularity due to its fast and impressing action. However, effectiveness and safety of iron sucrose in pregnant patient population is less clear. In this study, we aimed to review our intravenous iron sucrose use in pregnant patients.</p><p><strong>Study Design:</strong> The medical records of all anemic pregnant patients hospitalized for parenteral iron sucrose therapy were reviewed retrospectively.</p><p><strong>Results:</strong> The results of 117 pregnant women were available. Thirty-one (26.5%) and 86 (73.5%) of the patients were in the 2<sup>nd</sup> and 3<sup>rd</sup> trimester of the pregnancy, respectively. Four (%3.4) of the patients had severe and 113 (%96.6) of the patients had moderate anemia. The median gestational age for iron sucrose administration was 31.1 weeks (26.8-34.3). The mean hemoglobin, hematocrit and ferritin levels before and after delivery were 10.8±1.3 gr/l; 9.9±1.3 gr/l, 33.5±4.0; 30.8±4.0 and 89.6±0.7 μg/L; 98.1±0.9 μg/L, respectively. All but 2 (1.8%) patients had elevated hemoglobin levels after iron sucrose therapy. When hemoglobin and hematocrit levels were compared between before iron sucrose therapy and before delivery, there was a 2.8 g/l and 7.8 % increase in the mean hemoglobin and hematocrit levels, respectively and the difference was statistically significant (<em>p</em>= 0.001 and <em>p</em>=0.001, respectively). Five patients (4.3%) reported mild hypersensitivity reaction to intravenous iron in the form of mild itching at the infusion site. No severe or life-threatening hypersensitivity reaction was reported.</p><strong>Conclusion:</strong> In this study, we found out that intravenous iron sucrose therapy for iron deficiency anemia is feasible, effective and has a good safety profile.

Hepcidin Levels Predict Non-Responsiveness to Oral Iron Therapy in Patients with Iron Deficiency Anemia

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 484-484
Author(s):  
Lawrence T. Goodnough ◽  
David Morris ◽  
Todd Koch ◽  
Andy He ◽  
David Bregman
Keyword(s):  
Iron Deficiency ◽  
Iron Deficiency Anemia ◽  
Transferrin Saturation ◽  
Intravenous Iron ◽  
Oral Iron ◽  
Iron Therapy ◽  
Deficiency Anemia ◽  
Ferric Carboxymaltose ◽  
Predictive Values ◽  
Oral Iron Therapy

Abstract Abstract 484 Background Treatment options for individuals diagnosed with iron deficiency anemia (IDA) include oral or intravenous iron. Oral iron may not increase patient hemoglobin levels adequately, due to poor compliance and/or suboptimal gastrointestinal absorption due to inflammation-mediated induction of hepcidin, which regulates iron homeostasis. This study evaluated whether hepcidin levels can be used to identify patients with IDA who are unresponsive to oral iron therapy. Methods Hepcidin levels were assessed in a subset of subjects enrolled in a randomized trial comparing oral iron (ferrous sulfate) to intravenous iron (Injectafer®[ferric carboxymaltose, FCM]) in subjects with IDA (Hemoglobin [Hb] ≤ 11 g/dL; and ferritin ≤ 100 ng/mL, or ≤ 300 ng/mL when transferrin saturation (TSAT) was ≤ 30%) (Szczech et al Amer Soc Nephrol 2011; 22:405A). Subjects who met the inclusion criteria underwent a 14-day (run-in) course of ferrous sulfate 325 mg, three times per day. Subjects with an increase in Hb ≥ 1 g/dL were considered to be “responders” and not randomized. “Non-responders” were randomized to ferric carboxymaltose (2 injections of 750 mg given on Day 0 [day of randomization] and Day 7) or oral iron for 14 more days. Hb levels and markers of iron status were assessed at screening (day-15), day-1 and day 35. Hepcidin levels were analyzed at screening (Day -15) in an initial Cohort (I) of 44 patients, 22 responders and 22 non-responders. A hepcidin value of >20 ng/mL was identified for further analysis for predictive values for non-responsiveness to 14 day oral iron run-in in 240 patients (Cohort II). Hepcidin levels were also analyzed at Day -1 and Day 35 in a Cohort (III) of patients who were then randomized to FCM vs. oral iron therapy. Results Hepcidin screening levels in Cohort I were significantly higher in the non-responders vs. responders (33.2 vs. 8.7 ng/mL, p < 0.004). Twenty one of 22 non-responders had hepcidin values > 20 ng/mL. For Cohort II, mean hepcidin levels were again significantly higher in the non-responders vs. responders (38.4 vs. 11.3 ng/mL, p = 0.0002). Utilizing a hepcidin criterion of > 20 ng/mL, we found a sensitivity of 41.3% (26 of 150), specificity of 84.4% (76 of 90), and a positive predictive value (PPV) of 81.6% (62 of 76) for non-responsiveness to oral iron (Figure: The Receiver Operator Characteristic curves present plots of sensitivity vs. (1-specificity) for hepcidin, ferritin, and TSAT at the various cutoff levels indicated near the respective curves in the same color as the respective curves). While ferritin < 30ng/mL or TSAT <15% had greater sensitivity (77.3% and 64.7%, respectively), their PPVs (59.2% and 55%) were inferior to PPVs for hepcidin. Patients subsequently randomized to FCM vs. oral iron responded with Hgb increases of ≥1 g/dL for 65.3% vs. 20.8% (p <0.0001)and mean Hgb increases of 1.7 ± 1.3 vs. 0.6 ± 0.9 g/dL (p = 0.0025), respectively. Conclusion Our analysis provides evidence that non-responsiveness to oral iron in patients with iron deficiency anemia can be predicted from patients' baseline hepcidin levels, which have superior positive predictive values compared to transferrin saturation or ferritin levels. Furthermore, non-response to oral iron therapy does not rule out iron deficiency, since two thirds of these non-responders to oral iron responded to IV iron. Disclosures: Goodnough: Luitpold: Consultancy. Off Label Use: ferric carboxymaltose for treatment of iron deficiency anemia. Morris:Luitpold: Consultancy. Koch:Luitpold: Employment. He:Luitpold: Employment. Bregman:Luitpold: Employment.

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