Anemia Of Chronic Disease Patients Research Articles

Anemia of chronic diseases in the early stages of chronic kidney disease as a risk factor for cardiovascular complications in patients with glomerulonephritis

Aim. To determine biomarkers of anemia of chronic disease (ACD) in patients with glomerulonephritis (GN) in the early stages of CKD, to assess their role as risk factors for cardiovascular complications (CVС). Materials and methods. Seventy nine patients with GN were studied, among them: 40 with primary сhronic GN (CGN), 39 with secondary forms:19 – GN with ANCA-associated systemic vasculitis, 20 – GN with systemic lupus erythematosus (SLE) at early (all I–II) CKD stages. In all patients, the level of serum C-reactive protein (CRP), hepcidin, interferon γ, and the circulating form of protein Klotho (s-Klotho) were determined. When a relative iron deficiency was detected [transferrin iron saturation coefficient (TSAT) 20%], patients were administered parenterally iron [III] sucrose hydroxide complex (Venofer). Results. The frequency of anemia among patients with systemic diseases is 3.2 times higher than among patients with primary CGN. Patients with anemia (group I; n=43) had higher rates of daily proteinuria (p0.001), systolic blood pressure (p0.05), serum levels of interferon γ (p0.001) and hepcidin (p0.001) and lower values of eGFR (p0.05) than patients without anemia (group II; n=36). A strong inverse correlation was noted between the level of hepcidin and the content of iron in serum (r=-0.856; p0.001), between the level of hemoglobin and the level of interferon γ (r=-0.447; p0.05), hepcidin (r=-0.459; p0.05) and CRP (r=-0.453; p0.05). A significant inverse correlation was found between the level of hemoglobin and CVC risk factors – the value of systolic blood pressure (r=-0.512; p0.05) and the mass index of the left ventricular myocardium (r=-0.619; p0.01). At the same time, the contribution of 2 from 6 analyzed factors, hepcidin and eGFR, to the development of ACD was 92.5%, of which 86.6% accounted for hepcidin. A strong direct correlation was also found between a decrease in hemoglobin level and a decrease in the level of s-Klotho protein (r=0.645; p0.001), a decrease in the level of s-Klotho and an increase in the level of serum hepcidin (r=-0.541; p0.05). The leading value of anemia (beta -0,29; p=0,04) and depression of the s-Klotho level (beta -0,44; p=0,02) as independent cardiovascular risk factors in this group of patients was confirmed by multivariate analysis. In patients with identified deficiency of iron (n=40), after 3–4 weeks of intravenous administration of venofer, the target level of hemoglobin (Нb120 g/l) and transferrin saturation with iron (TSAT20%) were achieved. Conclusion. Among the biomarkers of ACD in patients with immunoinflammatory diseases of the kidneys (primary and secondary СGN), the increase in the serum level of hepcidin is greatest importance. The concomitant to anemia decrease in s-Klotho is a leading risk factor for CVС in CKD. Early correction of ACD with iron supplements makes it possible to achieve target levels of Hb and TSAT and have subsequently a positive effect on the production of s-Klotho and the severity of left ventricular hypertrophia.

Analysis of complete blood count parameters pre and post transfusion of packed red blood: A meta-analytic study in a tertiary care hospital

The clinical condition of anaemia is defined as reduction below normal limits of the total circulating red cell mass. It is measured by the reduction in packed red cell volume or reduction in haemoglobin concentration of blood. Patients with hemoglobin below 6 gm/dl usually require transfusion therapy. In stabilized patients with hemoglobin values between 6 and 10 gm/dl, the decision whether to transfuse is based on an evaluation of clinical status. The present study comprised of 140 Anaemic patients who received packed red cell transfusion. The study was analyzed for a period of one year. Haematological parameters – complete blood counts were collected by running anticoagulated blood in automated haematology analyser before and after transfusing the blood units. Peripheral smear by using Leishman’s stain. Reticulocyte count by using new methylene blue.Of total 140 patients, 45(34.6%) of patients were clinically diagnosed as iron deficiency anaemia followed by 43(33.1%) anaemia of chronic disease patients, 18(13.8%) of anaemia of chronic kidney disease, 20(15%) of anaemia of liver disease, 10(7.7%) of dimorphic anaemia (anaemia of combined deficiency) and 4(3.1%) of anaemia in hypersplenism.Iron deficiency anaemia is the most common disease group in the present study followed by anaemia of chronic disease. Anaemia is more prevalent in the female population with M:F ratio of 4:5. Particularly iron deficiency anaemia is more prevalent among females with M:F ratio of 1:3. After one unit of packed red cell transfusion the mean increase in Hb in IDA was 1.106gm/dl, in anaemia of ACD was 0.922gm/dl, in anaemia of CKD was 1.015gm/dl, in anaemia of liver disease was 0.614gm/dl in anaemia of combined deficiency was 0.925gm/dl and in hypersplenism was 0.367 gm/dl. From this background the present study concludes that before planning transfusion in anaemic patients, accurate clinical assessment and work up for type of anaemia is essential. After transfusion of one unit of packed red cells in chronic anaemia patients,. In all the types of anaemia studied, the mean increase in Hb and PCV values were statistically more significant (Pvalue<0.05) than other parameters. Hence Hb and PCV can be taken as valuable parameters to monitor the post transfusion outcome.

Clinical significance of serum hepcidin in the diagnosis and treatment of patients with anemia of chronic disease: a meta-analysis

Objective To systematically evaluate the value of serum hepcidin in the diagnosis of Anaemia of Chronic Disease (ACD) in order to provide appropriate treatment. Methods Literature search was performed in PubMed, EMbase, Cochrane Library, CNKI, CBMdisc and CSPD till Jan, 2020. Studies using hepcidin assay for the diagnosis of ACD were included. Two researchers selected the literature according to the pre-defined inclusion and exclusion criteria. Meta-analysis was performed using Stata 15.0. Results A total of 10 studies were included, including 739 patients with 402 ACD patients. Heterogeneity test results suggest that there is no statistical heterogeneity between the included studies and Meta- analysis was performed using a fixed-effects model. Results showed that serum hepcidin levels in patients with ACD combined with SEN, SPE, PLR, NLR, and Diagnostic OR were 0.94 [95% CI (0.90, 0.96)], 0.85 [95% CI (0.81, 0.88)], 6.1 [95% CI (4.8, 7.6)], 0.08 [95% CI (0.05, 0.12)] and 81 [95% CI (47, 139)] respectively. The area under the SROC curve (AUC) value was 0.91. Conclusion Serum hepcidin assay is a valuable method to diagnose ACD in patients. However, due to the limitations of the quantity and quality of the research, the above conclusions need more research to verify.

Anemia of Chronic Disease in Rheumatoid Arthritis and its Relationship with Disease Activities

Background: Rheumatoid arthritis is the most common form of inflammatory arthritis. Anemia is a common extra-articular manifestation and anemia of chronic disease (ACD) is the most common form of anemia in rheumatoid arthritis that reduces the quality of life.
 Objectives: The purpose of this study was to find out the prevalence of anemia of chronic disease (ACD) in Rheumatoid arthritis and to determine the relationship between ACD and disease activity of rheumatoid arthritis patients and to Identify the relationship between ACD and disease activity of rheumatoid arthritis patients.
 Methods: This was an observational cross-sectional study was conducted at the Department of Medicine, Rajshahi Medical College Hospital, Rajshahi. Consecutive 165 patients of rheumatoid arthritis with anemia who fulfilled the inclusion and exclusion criteria were enrolled in this study.
 Results: In this study mean age of these patients was 43.2±13.5 years. Male were 27(16.4%) and female 135(83.6%) with male: female ratio was 1:5.1. Most of the patients (29.1%) were illiterate, maximum participants (81.8%) were married and housewife 73.3%. DAS- 28 score (p< 0.001), tender and swollen joint count (p<0.001 for both tender and swollen joint count), ESR (p< 0.001) and HAQ score (p< 0.001) were significantly higher in anemic group of patients as compared to non-anemic. But there was no significant difference in terms of disease duration, morning stiffness and RF positivity between mentioned groups (p> 0.05). Comparing disease activity related characteristics between pure ACD and ACD with co-existent IDA sub group of patients, DAS 28 (p< 0.001), tender joint count (p= 0.03), swollen joint count (p= 0.03) and HAQ score (p= 0.03) were significantly higher in pure ACD patients than ACD and concomitant IDA patients with RA. But no significant difference was observed between two subgroups in terms of disease duration, morning stiffness, ESR and RF positivity (p> 0.05).Comparison of disease activity indices at different cut off levels between two groups and subgroups. Higher DAS- 28 score, tender joint count, swollen joint count and HAQ score was significantly found in anemic group of patients as compared to non-anemic. No significant difference was found between two groups at differing levels of morning stiffness (p= 0.337).
 Conclusions: ACD is frequently encountered with high frequency of iron deficiency anemia among rheumatoid arthritis patients and RA patients with anemic tend to have more severe disease than non-anemic RA patients.
 TAJ 2020; 33(2): 85-93

Predicting hepcidin level using inflammation markers and iron indicators in patients with anemia of chronic disease

BackgroundRecently, a small peptide called Hepcidin, was found to have an important role in regulating the iron metabolism in anemia of chronic disease (ACD) patients. Hepcidin is regulated by a variety of conditions at the transcriptional level. Therefore, our study aims to predict the level of hepcidin serum using inflammation markers and iron indicators in patients afflicted with ACD and observe how this severity of inflammation separated the level of interleukin-6 (IL-6), as well the as hepcidin level. MethodsA cross-sectional data analysis was conducted on 80 ACD adult patients treated at the Sanglah Teaching Hospital in Bali, Indonesia. We used hepcidin serum and several markers, such as the hemoglobin level, inflammation markers, renal function tests, IL-6, and iron indicators, to predict the hepcidin level. ResultsThis study recruited 80 ACD patients, comprising 45 men (56.3%) and 35 women (43.7%). The mean age of the participants was 43±16.5 years. Only IL-6, ferritin and serum creatinine correlate significantly with serum hepcidin from seven variables that were previously eligible to enter the analysis. This study found the model to predict the hepcidin level using IL-6 ferritin and the creatinine level as the hepcidin level (predicted)=−23.76+0.396 (IL 6)+0.448 (ferritin)+0.310 (creatinine). ConclusionThis study has revealed that the creatinine level, ferritin and IL-6 can be used to predict the hepcidin level in patients with anemia of chronic disease. It is to be hoped that further cohort studies can validate our formula to predict the hepcidin level.

Serum Soluble Transferrin Receptor-Ferritin Indices in Diagnosing and Differentiating Iron Deficiency Anemia from Anemia of Chronic Disease among Patients with Chronic Kidney Disease

Background: Anemia is common in patients with chronic kidney disease (CKD) and this is generally anemia of chronic disease (ACD), but iron deficiency anemia (IDA) is also common. Soluble transferrin receptor (sTfR) is a useful marker for IDA. Present study was undertaken to assess the utility of sTfR as a marker of IDA and to differentiate ACD from IDA in selected group of Bangladeshi patients with CKD.
 Methods: This cross-sectional study was conducted in the Department of Nephrology, BSMMU, Dhaka, Bangladesh from January 2013 to December 2014. Patients with anemia admitted in Nephrology Department, whether on hemodialysis or not and Medicine Department of BSMMU were taken for study. The study population was further divided into two groups; Group A, patients (30) who were having IDA and Group B, patients (40) with ACD and a control group was also selected. Data were collected by face to face interview and laboratory investigations with a self-administered questionnaire.
 Results: The mean age of the patients in Group A and Group B were 38.40±13.23 and 34.85±10.52 years respectively and male-female ratio were 0.5:1 and 1:0.5. Mean sTfR level was higher (4.81± 1.64 μg/ml) in patients with IDA than (2.89±1.40 μg/ml) in patients with ACD (p <0.0001). Mean ferritin level was 599.59± 449.15μg/L in ACD patients whereas 101.23±119.42 in IDA patients (p<0.0001). Total iron binding capacity (TIBC) was more in ACD patients with sTfRe”3μg/ml as compared to ACD patients with sTfR<3μg/ml. Transferrin saturation (TSAT) level was significantly decreased in ACD patients with sTfRe”3μg/ml as compared to ACD patients with sTfR<3μg/ml. sTfR and ferritin indices between group A (IDA) and group B (ACD) shows mean sTfR:logSF level was significantly (P<0.001) high in group A (2.71±1.13) in comparison to group B (1.08±0.54). Mean log sTFR:SF was also significantly higher (P<0.05) in group A (0.001±0.0008) compared to group B (0.013±0.012).
 Conclusion: sTfR level has a comparable ability to serum ferritin in diagnosing IDA and ACD. However, sTfR and serum ferritin alone cannot definitely exclude coexisting iron deficiency in ACD. Log sTfR/ ferritin index has role in identifying development of iron deficiency in ACD whereas sTfR/ log SF ratio can differentiate pure IDA from ACD with or without iron deficiency. Thus, it is important to estimate both serum sTfR and sTfRferritin indices to be able to differentiate pure IDA, ACD and ACD with co-existing iron deficiency thus providing a non-invasive alternative to bone marrow iron.
 Birdem Med J 2019; 9(2): 151-156

Indicators of iron exchanges in patients with chronic obstructive pulmonary diseases

Мета роботи — провести аналіз основних показників обміну заліза у хворих на хронічне обструктивне захворювання легень (ХОЗЛ). Матеріал і методи. У дослідження включено 202 хворих на ХОЗЛ віком > 40 років. Хворих було розподілено на чотири досліджувані групи залежно від показників гемограми: 1‑шу групу склали 144 пацієнти без анемії, 2‑гу групу — 33 із анемією хронічного захворювання (АХЗ), 3‑тю групу — 12 із еритроцитозом та 4‑ту групу — 13 із залізодефіцитною анемією (ЗДА). Всім обстеженим пацієнтам проводили загальноклінічні, лабораторні, інструментальні дослідження. До комплексу лабораторних обстежень включали дослідження вмісту сироваткового заліза (СЗ), загальної залізозв’язувальної здатності сироватки крові (ЗЗЗЗ), ненасиченої залізозв’язувальної здатності сироватки крові (НЗЗЗ), трансферину, феритину, еритроцитарних індексів та кольорового показника (КП). Результати. Середній oб’єм еритрoцитів виявився нижчим у групі хворих на ХОЗЛ із ЗДА та в межах референтних значень серед хворих на ХОЗЛ із АХЗ. Середній вміст гемoглoбіну в еритрoциті, середня кoнцентрація гемoглoбіну в oб’ємі еритрoцитів та КП були в межах референтних значень у хворих на ХОЗЛ без анемії, з АХЗ та еритроцитозом та знижені у хворих на ХОЗЛ із ЗДА. АХЗ у хворих на ХОЗЛ є нормоцитарною та нормохромною, ЗДА — мікроцитарною та гіпохромною. Нами було встановлено, що хворі на ХОЗЛ із ЗДА мали низький вміст СЗ та феритину, та високий вміст ЗЗЗЗ, НЗЗЗ та трансферину. У групі хворих на ХОЗЛ із АХЗ виявлено вміст СЗ у межах референтних значень та низький вміст ЗЗЗЗ, НЗЗЗ та трансферину одночасно із високим вмістом феритину. Висновки. Анемія хронічного захворювання спостерігається у 16,3% хворих на хронічне обструктивне захворювання легень та є нормоцитарною та нормохромною. Залізодефіцитна анемія у хворих на хронічне обструктивне захворювання легень виявляється у 6,4% хворих. Низький вміст сироваткового заліза, загальної залізозв’язувальної здатності сироватки крові, ненасиченої залізозв’язувальної здатності сироватки крові та трансферину одночасно з підвищеним вмістом феритину у хворих на хронічне обструктивне захворювання легень є характерним для анемії хронічного захворювання; низький вміст сироваткового заліза та феритину та підвищений вміст загальної залізозв’язувальної здатності сироватки крові, ненасиченої залізозв’язувальної здатності сироватки крові та трансферину є характерним для залізодефіцитної анемії. Хворі на хронічне обструктивне захворювання легень без анемії та з еритроцитозом мають еритроцитарні індекси, кольоровий показник та показники обміну заліза в межах референтних значень.

Diagnostics in anaemia of chronic disease in general practice: a real-world retrospective cohort study.

BackgroundLimited research has been performed that focused on the diagnosis of the underlying cause of anaemia of chronic disease (ACD) in general practice or on prevalence data of the underlying causes of ACD in general practice, although this is one of the most common types of anaemia.AimTo clarify the diagnostic strategies of GPs in patients newly diagnosed with ACD and to determine the most common underlying causes.Design & settingRetrospective cohort study.MethodPatients newly diagnosed with ACD were selected based on laboratory criteria. ACD was defined as confirmed anaemia and ferritin levels above 100 μg/l combined with decreased iron and/or reduced transferrin. Additional medical information on patients was obtained from the electronic medical files of the GP and/or the referral hospital.ResultsOf the 267 analysed patients with ACD, additional investigations were performed in 205 patients (77%); in 31 patients (12%) the cause was apparent at the time of diagnosis, and for 31 patients (12%) no additional investigations were requested. In 210 (79%) of the 267 patients, an underlying cause was established, with infection (n = 68, 32%), autoimmune disease (n = 51, 24%) and malignancy (n = 48, 23%) as the most frequently observed etiologies. In 35 (13%) of the ACD patients, oral iron supplementation was prescribed by the GP. This was mainly done in patients with severe anaemia or less enhanced ferritin levels.ConclusionFor most patients with newly diagnosed ACD, the GP undertakes additional investigations to establish underlying causes. However, the cause of ACD remains unknown in a small proportion of patients. The use of oral iron supplementation in these patients requires caution.

Effects of Sucrosomial® iron in Pre-Clinical and Clinical Conditions of Inflammation

Introduction: Proteins such as Ferritin (Ft), Hemoglobin (Hb) and Transferrin Receptor (TfR1) are involved in tissue iron distribution while systemiciron metabolism is regulated by Hepcidin. Interleukin-6 (IL-6) release is induced in response to an inflammatory status and enhances Hepcidin expression, as consequence, dietary iron absorption and macrophage iron recycling are inhibited. Anemia of Chronic Disease (ACD) is a form of anemia associated with many different chronic disorders. It is characterized by high hepcidin and CRP or IL-6 expression and low serum iron transferrin concentration while ferritin can be normal or elevated. Oral iron delivery is especially attractive thanks to the ease of administration, but commonly used iron salts are poorly absorbed and ineffective to increase Hb concentration in particular in patients with ACD. We have developed an oral Iron formulation named Sucrosomial® Iron, preparation of ferric pyrophosphate, covered by a phospholipids plus sucrester matrix, with high bioavailability and tolerability, which promotes ferric iron absorption thanks to gastro-resistant and matrix composition properties and showed Hb concentration improvement not inferior to intravenous iron.Objective: to showpre-clinical and clinical evidences of absorption, effectiveness and tolerability of Sucrosomial Iron using in vivo and in vitro models and in patients with ACD too.Methods: To study the effects of oral supplementation on Iron metabolism and inflammatory status, Hb, Ft, TfR1, Socs3 and Hepcidin expression were analyzed. We have supplemented wild-type (wt) and iron deficient (ID) mice, maintained in iron-free diet for 8 weeks, with 1mg/kg/die of Sucrosomial® Iron or Iron Sulfate or Placebo by oral gavage, for 2 weeks. The role of Sucrosomial® Iron on the inflammatory response, was studied in LPS induced HepG2 hepatoma cells. Cells were treated with Sucrosomial® Iron and the levels of hepcidin were assessed 6, 18 and 24 hours after treatment. To show the efficacy and compliance of Sucrosomial® Iron a multi-centric randomized study on 300 patients with ACD were performed. Patients were supplemented with iron sulfate (65 mg o.i.d.), microencapsulated iron, micronized iron, Sucrosomial® Iron, heminic-chelated bisglycinated and iron chelated bisglycinated iron (30 mg t.i.d.). Median Hb value at the beginning was 8.2 g/dl. In group of patients with high CRP value median Hb value was 7.8 g/dl.Results: In mice treated with Sucrosomial® Iron, Hb level mean increase was 4,9 g/dl while TSAT value is not significantly higher than animals treated with Sulfate Iron. Furthermore mice treated with Sucrosomial® Iron showed a preferential accumulation of iron in spleen. Hepcidin and Socs3 mRNA expression was not induced during Sucrosomial® Iron treatment while was up-regulated in mice treated with Iron Sulfate (Figure 1). In vitro experiments on HepG2 LPS-induced cells displayed that treatment with Sucrosomial Iron® is able to reduce hepcidin concentration at different time points (Figure 2).Data from the clinical study showed that Sucrosomial® Iron is well tolerate and effective ACD patients. Only patients treated with Sucrosomial® Iron showed constant increase in Hb concentration over time. In all groups Hb level achieves a plateau phase after three months and ferritin level starts to increase. At three months higher levels of Hb are present in Sucrosomial® Iron (13.2 g/dl), heminic chelated bisglycinated iron (11.7 g/dl), chelated bisglycinated iron (11.3 g/dl) treated patients. In patients with high CRP level (>30 ng/ml) only those receiving Sucrosomial® Iron showed Hb increase from the tenth week and this continue up to the sixth month (Hb 12.5 g/dl) and seems to be correlated to a significantly decrease of CRP (5 mg/L) (Figure 3). Side effects are higher in ferrous sulfate (15/50) and sunactive treated groups (6/60).Conclusions: In summary, results showed that Sucrosomial® Iron treatment could regulate iron homeostasis through an increase in Hb concentration and better tolerability during inflammatory status. These evidences may suggest that this new oral iron formulation behaves differently than other oral iron salts, perhaps due to different absorption pathways. Besides we have observed a decrease in CRP and Hepcidin concentration, these results should be further investigate. [Display omitted] DisclosuresBrilli:Pharmanutra S.p.A.: Consultancy. Pera:Pharmanutra S.p.A.: Employment. Tarantino:Pharmanutra S.p.A.: Employment.

Hepcidin and iron parameters in children with anemia of chronic disease and iron deficiency anemia

BackgroundAnemia of chronic disease (ACD) and iron deficiency anemia (IDA) are the two most prevalent forms of anemia having interrelated characteristics. Hepcidin, a newly introduced biomarker for assessment of iron status, is a homeostatic regulator of iron metabolism. We investigated the role of hepcidin and other conventional iron parameters to assess iron status among children with ACD and IDA. We also identified children with ACD who developed iron deficiency (ID).MethodsThe study was undertaken in anemic children with 30 cases each of ACD and IDA along with 30 age and sex-matched controls. The ACD cases were subdivided into pure ACD and ACD with coexistent ID. All cases were subjected to following tests: complete blood count with peripheral smear, serum C-reactive protein, serum interleukin-6, iron studies, serum soluble transferrin receptor (sTfR), and serum hepcidin.ResultsThe mean serum hepcidin concentration was significantly increased in pure ACD patients (143.85±42.76 ng/mL) as compared to those in IDA patients (6.01±2.83 ng/mL, P < 0.001) and controls (24.96±9.09 ng/mL, P <0.001). Also, compared to pure ACD patients [normal sTfR levels (<3 µg/mL)], the serum hepcidin concentration was reduced significantly in ACD patients with ID [high sTfR levels (≥3 µg/mL)] with a mean of 10.0±2.97 ng/mL.ConclusionHepcidin measurement can provide a useful tool for differentiating ACD from IDA and also help to identify an iron deficiency in ACD patients. This might aid in the appropriate selection of therapy for these patients.

Recent Versus Conventional Iron Status Parameters for Diagnosis of Anemia in Juvenile Idiopathic Arthritis Patients

▪Objective: Juvenile Idiopathic Arthritis (JIA) is commonly associated with different types of anemia. The diagnosis and treatment of IDA is a medical necessity; being a well-recognized cause of both short and long term morbidity plus being strongly related to poor disease outcome. In the presence of concomitant chronic illness or inflammation, the diagnosis of iron deficiency using the conventional laboratory parameters is a major medical challenge. Therefore, the utility of two recent iron status parameters; hepcidin-25 "active form of iron metabolism negative regulator" and reticulocyte hemoglobin content (CHr) "functional anemia indicator" was compared to that of two conventional ones; transferrin saturation (TSAT) and red cell distribution width percentages (RDW%) in diagnosing iron deficiency anemia in patients with JIA.Methods: Blood samples were obtained from 43 JIA patients whose ages ranged from 3 to 16 years and 20 age and sex matched healthy children as control group. Three different types of anemia; iron deficiency anemia (IDA), anemia of chronic disease (ACD) and combined anemia (IDA/ACD) were identified within the studied patients using iron profile, ESR and C-reactive protein. Serum hepcidin-25 was assessed by ELISA technique; CHr, TSAT% and RDW% were all estimated using Siemens ADVIA 2120 analyzer in patients and the control group.Results: Anemia was identified in 22 (51.2%) patients. Serum hepcidin-25 and TSAT% were significantly lower in IDA than ACD & IDA/ACD patients (p= 0.032 and p=0.034 for hepcidin and p= 0.004 and p=0.012 for TSAT%). Significantly lower CHr and higher RDW% were found in IDA/ACD compared to ACD patients (p= 0.032 and p< 0.001, respectively). Serum hepcidin ≤ 3.8ng/mL and TSAT% ≤ 5.8% differentiated IDA from both ACD and IDA/ACD with 80 and 100% sensitivity and 88.24% specificity. CHr ≤24.4pg and RDW % > 16.4% showed 80 and 90% sensitivity and 100% specificity; distinguishing IDA/ACD from ACD.Conclusion: Serum hepcidin and CHr were not superior to TSAT% and RDW%; discriminating among different types of anemia in JIA patients.Table 1Comparison between anemia subgroups according to CHr and serum hepcidinIDA(n=5)ACD(n=6)Combined anemia(n=7)Control(n=20)pCHr (pg)23.61 ± 3.80a27.36 ± 2.30b23.37 ± 3.18a30.54 ± 1.99<0.001*Serum hepcidin (ng/ml)3.60 (3.0-4.9)bc5.10 (3.10 - 90.0)7.15 (3.1-60.0)5.0 (0.10-10.8)0.121Data was expressed as Mean ± SD. for normally distributed data and Median (Min. - Max.) for abnormaly distrbutied dataa: Significant with control gorupb: Significant with combined anemia groupc: Significant with ACD groupTable 2Comparison among anemia subgroups and control group according to RDW & TSAT%IDA(n=5)ACD(n=7)Combined anemia(n=10)Control(n=20)Test of sig.pRDW%Min. - Max.17.30 - 19.9013.10 - 16.4015.60 - 22.012.40 - 15.80F=45.032*<0.001*Mean ± SD.18.42 ± 1.0414.49 ± 1.3018.46 ± 1.9213.47 ± 0.86Median2.6213.9018.2013.10Sch p*p1<0.001* ,p2=0.362,p3<0.001* ,p4=1.000,p5<0.001* ,p6<0.001*TSAT %Min. - Max.4.20 - 5.806.0 - 20.504.40 - 26.011.0 - 40.0KW χ2 =*<0.001*Mean ± SD.4.78 ± 0.6410.73 ±4.8213.82 ± 8.6322.71 ± 8.32Median4.5010.012.8020.70MW p10.001*0.001*0.016*MW p20.012*0.660MW p30.004*KW c2 : Chi square for Kruskal Wallis test F: F test (ANOVA)p1: p value for comparing between control and IDAp2: p value for comparing between control and ACDp3: p value for comparing between control and combined anemiap4: p value for comparing between combined anemia and IDAp5: p value for comparing between combined anemia and ACDp6: p value for comparing between ACD group and IDA groupMW: Mann Whitney test Sch: Post Hoc Test (Scheffe)*: Statistically significant at p ≤ 0.05Table 3Agreement (sensitivity, specificity and accuracy) for serum hepcidin and TSAT% with IDA vs. ACD and combined anemia in JIA patientsACD and combined anemiaIDASensitivitySpecificityPPVNPVAccuracySerum hepcidin (ng/ml)>3.815180.088.2466.6793.7586.36<3.824TSAT%>5.8150100.088.2471.43100.090.91≤5.825Table 4Agreement (sensitivity, specificity and accuracy) for CHr and RDW% with ACD vs. combined anemia in JIA patientsACDCombined anemiaSensitivitySpecificityPPVNPVAccuracyCHr>24.47280100.0100.077.7888.24≤24.408RDW %≤16.47190.0100.0100.087.5094.12>16.409 DisclosuresNo relevant conflicts of interest to declare.

Anemia of Chronic Disease in Rhenumatoid Arthritis And Its Realationship With Disease Activities

Anemia is a frequent cause of morbidity in patients with Rheumatoid Arthritis (RA) that reduces quality of life. This observational cross sectional study was carried out in Rheumatology OPD and Medicine Indoor of Bangabandhu Sheikh Mujib Medical University (BSMMU) from January 2009 to December 2010 to find out the frequency of Anemia of Chronic Disease (ACD) and relative frequency of pure ACD and ACD with coexistent Iron Deficiency Anemia (IDA) in RA and to describe the relationship between ACD and disease activity of RA patients. For this purpose a total of 130 RA patients were enrolled according to the inclusion and exclusion criteria of the study and divided into ACD group and non anemic group on the basis of hemoglobin level (11g/dl in females and &lt;12g/dl in males). ACD group of patients again divided into pure ACD and ACD with co-existent IDA subgroups on the basis of ratio of Soluble Transferrin Receptor (sTfR) to log ferritin (sTfR­F index).Patients with sTfR-F index value&lt;1 were classified as pure ACD and sTfR-F index value &gt;1 were classified as ACD with coexistent IDA. Disease activity were assessed by modified Disease Activity Score (DAS-28), Tender joint count, Swollen joint count, Morning stiffness in minutes, Health Assessment Questionnaire (HAQ) Erythrocyte Sedimentation Rate (ESR) in mm in 1st hour and Rheumatoid Factor (RF) positivity. Out of 130 patients, estimated frequency of ACD was 59%.Among the ACD patients, 16% were found to have pure ACD and 84% had both ACD and IDA. Disease activity parameters were compared between ACD group and non anemic group and then pure ACD and ACD with co­existent IDA subgroups of patients. We found significantly higher mean DAS-28 score ,tender joint count, swollen joint count, HAQ score and mean ESR in ACD group of patients as compared to non anemic RA patients. When differing levels of disease activity indices were compared, we also found significant difference between ACD and non anemic groups. Patients with pure ACD subgroups had significantly higher mean DAS-28, tender joint count, swollen joint count and HAQ score as compared to ACD with co-existent IDA subgroups of patients. When comparing differing levels of disease activity indices, no significant difference was observed between pure ACD and ACD with coexistent IDA patients with RA. This it can be said in conclusion that ACD is frequently encountered with high frequency of iron deficiency anemia among rheumatoid arthritis patents. RA patents with ACD tend to have severe disease than non anemic RA patents but pure ACD patints not necessarily had severe disease as compared to combined ACD and IDA. JCMCTA 2015 ; 26 (1) : 14-20

A Case of Subacute Combined Degeneration of the Spinal Cord with Infective Endocarditis.

Background. Subacute combined degeneration (SCD) is a rare cause of demyelination of the dorsal and lateral columns of spinal cord and is a neurogenic complication due to cobalamin deficiency. Anemia of chronic disease (ACD) occurs in patients with acute or chronic immune activation, including infective endocarditis. It remains to be elucidated whether ACD patients are more sensitive to suffer from SCD. Little cases about SCD patients accompanied with ACD have been reported till now. Here we reported a 36-year-old man with SCD with a medical history of mitral inadequacy over 20 years, who was admitted and transported from another hospital to our hospital due to an 8-month history of gait disturbance, lower limb weakness and paresthesia, and loss of proprioception. Significant laboratory results and echocardiography suggest iron deficiency anemia and infective endocarditis (IE). The SCD diagnosis was confirmed by MRI, which showed selective demyelination in the dorsal and lateral columns of spinal cord. In conclusion, the ACD patients may suffer from SCD, which can be diagnosed by 3 Tesla magnetic resonance imaging.

Screening For Hereditary Spherocytosis: EMA Binding Test and Flow Cytometric Osmotic Fragility Test Are Recommended, But Cryohemolysis Test Is Not Recommended

BackgroundThe hallmark of laboratory test for the diagnosis of hereditary spherocytosis (HS) has been osmotic fragility (OF) test. However, OF test gives false negative results in 10% - 20% of HS patients and false positive results in autoimmune hemolytic anemia (AIHA) patients. Currently, the eosin 5-maleimide (EMA) binding test and hypertonic cryohemolysis (HCH) test have been proposed as screening tests in recently published guidelines for the diagnosis of HS (Br J Haematol 2012;156:37-49). And the flow cytometric OF (FC OF) test is recently developed as an assay that can replace the classical OF test. In this study, we evaluated the performance of 3 screening tests (EMA binding test, FC OF test, and HCH test) for the diagnosis of HS. MethodsA total of 151 patients [32 for HS, 40 for AIHA, 40 for anemia of chronic disease (ACD), 39 for iron deficiency anemia (IDA)] and 140 normal controls (NCs) were enrolled in this study. EMA binding test, FC OF test, and HCH test were performed separately in each patient. Reference ranges (mean ± 1.96SD or 2.5th – 97.5th percentile) for each test were determined from 140 NCs. The cutoff value in EMA binding test (5th percentile) was estimated from 119 anemia patients (AIHA+ACD+IDA), and those in FC OF test (mean -1.65SD) and HCH test (95th percentile) were calculated from 140 NCs. Sensitivity, specificity, negative predictive values (NPV), positive predictive values (PPV), and accuracy of each test were calculated using these cutoff values and compared. Subsequently, receiver operating characteristics (ROC) analysis were performed to determine the best cutoff values of each test for the discrimination of HS from other anemia and area under curve (AUC) of three tests were compared. ResultsThe reference ranges of EMA binding test, FC OF test, and HCH test were determined as 86.9% - 118.68%, 6.6% - 71.6%, and 1.5% - 11.8%, respectively, and estimated cutoff values for the diagnosis of HS were calculated to be< 89.4% (EMA binding test),< 8.0% (FC OF test), and > 9.8% (HCH test). In the EMA binding test, HS patients showed significantly decreased EMA binding to RBC (median 71.3%) than AIHA (median 102.0%, P< 0.001), ACD (median 103.7%, P< 0.001), and IDA (median 100.5%, P< 0.001) patients. In the FC OF test, HS patients also showed significantly decreased residual RBC% (median 3.0%) than AIHA (median 44.6%, P< 0.001), ACD (36.0%, P< 0.001), IDA (median 59.4%, P< 0.001) patients and NCs (median 25.2%, P< 0.001). In the HCH test, HS patients showed significantly increased hemolysis (median 10.2%) than AIHA (median 3.6%, P< 0.001) and ACD (median 4.2%, P< 0.001) patients and NC (median 4.7%, P< 0.001), but IDA patients (median 16.4%) showed significantly increased hemolysis than HS patients (P = 0.027). The sensitivity/specificity/NPV/PPV/accuracy of three tests for the discrimination of HS from other anemia using estimated cutoff values mentioned above were calculated as 96.9%/95.0%/99.1%/83.8%/95.4% for EMA binding test, 84.4%/96.6%/95.8%/87.1%/94.0% for FC OF test, and 50.0%/73.1%/84.5%/33.3%/68.2% for HCH test. When the best cutoff values (≤ 85.0% for EMA binding test, ≤ 10.8% for FC OF test, > 7.1% for HCH test) obtained from ROC analysis are applied, both EMA binding test (AUC 0.996) and FC OF test (AUC 0.986) showed satisfactory performance for the discrimination of HS from other anemia. However, HCH test (AUC 0.703) showed significantly poor performance compared than EMA binding test (P< 0.001) and FC OF test (P< 0.001). ConclusionDespite the current guideline recommends EMA binding test and HCH test as screening tests for the diagnosis of HS, our present results demonstrated that both EMA binding test and FC OF test possess satisfactory performance for the diagnosis of HS but HCH test has relatively poor performance compared to the EMA binding test or FC OF test and failed to discriminate HS patients from IDA patients. These results partly contradict the recommendations from HS guideline and therefore, both EMA binding test and FC OF test is recommended as screening tests for the diagnosis of HS, but HCH test is not recommended. Disclosures:No relevant conflicts of interest to declare.

The relationship between the iron isotopic composition of human whole blood and iron status parameters

As the iron status of an individual cannot be adequately assessed on the basis of the (total) Fe concentration in whole blood or serum, in medicine a number of parameters, such as the serum concentrations of ferritin, transferrin and soluble transferrin receptor and the transferrin saturation, are routinely determined instead. As previous research has shown that also the isotopic composition of Fe in blood and tissues is dependent on the metabolism, the present study assessed whether Fe isotopic composition in whole blood provides information as to an individual's iron status. Fe isotopic analysis of whole blood samples from a reference population (healthy volunteers) was carried out using multi-collector ICP-mass spectrometry (after chromatographic target element isolation) and the results obtained were investigated by statistical means as to their potential relation with the iron status parameters conventionally used in medicine. A low δ(56)Fe value was demonstrated to coincide with high iron status and a high δ(56)Fe value with low iron status, thus reflecting the response of the body to this iron status in terms of iron uptake, distribution between blood and stores and mobilization of storage iron. In a second phase, the iron isotopic composition in blood from patients treated for hemochromatosis type I and from patients with anemia of chronic disease (ACD) was determined. The results for hemochromatosis patients plotted with the values of low iron status, while those for ACD patients plotted with the values of high iron status. By taking a closer look at the aberrant iron metabolism that comes with these diseases, it can be seen that the patient samples confirm the conclusions drawn for the reference population. Patients with hemochromatosis type I have a strongly upregulated iron uptake, like healthy individuals with low iron status. The metabolism of patients suffering from ACD tries to remove iron from the circulation by downregulating the iron uptake, moving more absorbed iron to the stores and by not using any iron from these storage sites, which is in agreement with the responses of the human body to high iron status. This suggests that the conclusions made for healthy individuals are extendable to patients with aberrant iron metabolism.

Hepcidin is a key mediator of anemia of inflammation in Crohn's disease

Anemia often complicates the course of Inflammatory Bowel Disease (IBD). Hepcidin, a liver-produced peptide hormone, is a key mediator of anemia of chronic disease (ACD). We hypothesized that hepcidin is significantly elevated in anemic CD patients and that hepcidin may cause iron restriction and, therefore, mediate ACD. MethodsWe enrolled 17 patients with CD and ACD recruited from the Cedars-Sinai IBD Center. Routine blood tests included hemoglobin (Hgb), hematocrit, erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP). Anemia was defined as hemoglobin <12g/dL and <13.5g/dL, in men and women, respectively. ACD was diagnosed on the basis of a combination of the following: a) normal or elevated ferritin b) lowered serum iron and total iron binding capacity and c) normal percent iron saturation. Serum and urine hepcidin, as well as IL-6 levels were also measured. Patients with documented iron-deficiency anemia were excluded. ResultsThere was an excellent correlation between urine (expressed as ng/mg of creatinine) and serum hepcidin levels expressed as ng/ml (r=0.853, p<0.001). We also found a strong positive correlation between serum hepcidin and ferritin levels (r=0.723, p=0.0015). There was a positive correlation between serum hepcidin and IL-6 levels (r=0.546, p=0.023). We found a strong negative correlation between serum hepcidin concentrations and Hgb levels (r=0.528, p=0.029). ConclusionWe demonstrate that ACD in CD is characterized by high serum IL-6 and hepcidin levels, which negatively correlate with Hgb levels. Our data support the hypothesis that IL-6-driven hepcidin production mediates ACD in patients with CD.

Prevalence of 25-Hydroxyvitamin D Deficiency in Korean Patients with Anemia

AbstractAbstract 5164 Background:Vitamin D deficiency is a very common health problem in Korea. Vitamin D has been suggested to have an important role on nonskeletal functions including cellular proliferation and differentiation, muscle function, immunity and erythropoiesis. Recent studies have been reported that vitamin D deficiency had associated with iron deficiency anemia, anemia of chronic kidney disease, and anemia of inflammation. In this study, we investigated the prevalence of vitamin D deficiency in Korean patients with anemia and also analyzed the association between vitamin D status and specific subtypes of anemia. Methods:A total of 147 anemic patients (median age 66 years, range 19∼91 years) and 300 nonanemic controls (median age 60 years, range 29∼87 years) were included. Anemia was defined according to World Health Organization (WHO) criteria. Serum 25- hydroxyvitamin D [25(OH)D] was measured using electrochemiluminescence immunoassay. The deficiency of 25(OH)D was defined as <20 ng/mL and severe deficiency was defined as <10 ng/mL. We compared serum 25(OH)D levels based on the presence and subtypes of anemia. Results:The prevalence of 25(OH)D deficiency was 74% (109/147) and 70% (210/300) in anemic (median Hb 9. 6 g/dL) and nonanemic group (median Hb 14. 3 g/dL), respectively. The prevalence of severe 25(OH)D deficiency was significantly higher in anemic group than in nonanemic group [44. 8% (66/147) vs 11. 7% (35/300), P<0. 0001] Odds ratio for severe 25(OH)D deficiency in anemic patients was 6. 17 (95% CI 3. 820–9. 965, P<0. 0001). The prevalence of 25(OH)D deficiency was not different between iron deficiency anemia (IDA) group and anemia of chronic disease (ACD) group. However, the serum 25(OH)D levels of ACD patients were lower than those of IDA patients in male (median 25(OH)D 14. 34 ng/mL vs 23. 04 ng/mL, P=0. 04). Conclusion:This study demonstrates that severe vitamin D deficiency is associated with anemia in Korea. Although vitamin D deficiency is also very common in nonanemic Korean population, anemia is related to much worse vitamin D deficient status. Multiple factors including poor nutritional status and potential roles of vitamin D on inflammation and erythropoiesis might be considered. Disclosures:No relevant conflicts of interest to declare.

Single and Repeated Dose First-in-Human Study with the Anti-Hepcidin Spiegelmer Nox-H94.

AbstractAbstract 2342 Background:NOX-H94, the first-in-class hepcidin inhibitor in development for treatment of anemia of chronic disease (ACD), is a PEGylated anti-hepcidin L-RNA oligonucleotide. ACD is caused by iron sequestration in the reticulo-endothelial macrophages with subsequent iron restricted erythropoiesis due to high hepcidin production and subsequent ferroportin degradation. The treatment of ACD is challenging: a significant number of ACD patients do not respond to erythropoiesis stimulating agents (ESAs), while repeated intravenous iron administrations bear a risk of iron overload. Targeting hepcidin may provide more efficacious and well tolerated treatment alternatives. Methods:This First-in-Human study investigated the safety and tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of escalating single and repeated doses of intravenous (i.v.) NOX-H94 in healthy men and women. The study protocol (ClinicalTrials.gov identifier NCT01372137) was approved by an independent ethics committee and conducted in accordance with the Declaration of Helsinki. Five successive cohorts of 8 healthy subjects, at least 3 men and women, were randomly assigned to i.v. doses of 0.3, 0.6, 1.2, 2.4, and 4.8 mg/kg of NOX-H94 (n=6) or placebo (n=2). Similarly, 2 cohorts of 8 male subjects randomly received 5 doses of either 0.6 or 1.2 mg/kg NOX-H94 or placebo every other day (q2d). Safety parameters, iron parameters, total hepcidin-25 (sum of free circulating hepcidin-25 and hepcidin-25 bound to NOX-H94), and PK were assessed during treatment and follow-up periods of ≥3 weeks. Data are given as means±SD. Results:One man, assigned to 5 i.v. doses of 0.6 mg/kg, withdrew consent after 4 administrations; all other 55 subjects completed the study as scheduled. Safety: Treatment with NOX-H94 was generally safe and well tolerated. No serious adverse event occurred; headache and fatigue were the only treatment related events that occurred more than once. Mild and transient increases in transaminases (<2×ULN) were noted in subjects treated with NOX-H94 at single doses ≥2.4 mg/kg or with repeated doses of 1.2 mg/kg (4.2 mg/kg weekly). PK: After escalating single i.v. administrations of 0.3 to 4.8 mg/kg of NOX-H94, peak plasma concentrations of NOX-H94 (Cmax) and systemic exposure (AUC) increased dose-proportionally. The elimination was bi-phasic with a terminal plasma half-life (t ½) in the range of 17 to 26 h. The systemic clearance (CL) was low (Table 1). After repeated q2d i.v. administrations, no appreciable plasma accumulation was found based on Cmax and AUC. No obvious gender-difference was observed. PD: The plasma concentration of total hepcidin-25 increased dose-dependently upon NOX-H94 treatment, without ever exceeding the plasma concentration of NOX-H94. The PD effects were assessed by analysis of the area under the data time curve above baseline (AUD) of various iron parameters. Single and repeated doses of NOX-H94 up to 0.6 mg/kg had no effect on serum iron, serum ferritin, and transferrin saturation (TSAT) in the healthy subjects studied. At doses ≥1.2 mg/kg NOX-H94, serum iron, serum ferritin, and TSAT increased dose dependently.Table 1:Single dose PK of NOX-H94Dose Group [mg/kg]nCmax [μM]AUC 0-tlast [μM×h]t ½ [h]CL [L/h]0.360.524±0.0985.63±3.4316.5±7.50.34±0.220.661.09±0.36013.0±4.5518.0±7.50.24±0.101.262.17±0.26130.4±6.2423.9±9.90.18±0.032.464.75±0.67980.0±12.023.5±4.40.15±0.034.869.85±1.53213±26.526.3±3.20.12±0.03Table 2:Serum iron parameters after single dose treatment with NOX-H94 analyzed based on the area under the data time curve above baseline (means±SD)Dose Group [mg/kg]nSerum iron [μmol/L×h]Serum ferritin [μg/L×h]TSAT [%×h]Placebo1044.6±28.429.5±45.362.5±41.00.3647.6±51.915.5±31.382.2±76.90.6667.0±40.344.4±53.2111±60.11.26193±53.7125±205321±1372.46134±45.0371±290239±97.84.86225±138644±670422±334 Conclusions:Treatment with NOX-H94 was generally safe and well tolerated over all dose levels and schedules studied; for subsequent phase II studies in patients, twice weekly i.v. doses of 1.2 mg/kg are recommended. PK analyses showed a dose-linear systemic exposure. In these healthy subjects, only mild dose-dependent increases in iron parameters were observed which likely underestimate the effects that may be obtained in patients with iron-restricted anemia. Disclosures:Riecke:NOXXON Pharma AG: Employment. Zöllner:NOXXON Pharma AG: Employment. Vauléon:NOXXON Pharma AG: Employment. Swinkels:NOXXON Pharma AG: Research Funding. Dümmler:NOXXON Pharma AG: Employment. Summo:NOXXON Pharma AG: Employment. Schwoebel:NOXXON Pharma AG: Employment. Fliegert:NOXXON Pharma AG: Employment.

Is analysis of the reticulocyte haemoglobin equivalent a useful test for the diagnosis of iron deficiency anaemia in geriatric patients?

BackgroundIron deficiency anaemia (IDA) and anaemia of chronic disease (ACD) are common in elderly patients but there are no standard diagnostic criteria. The reticulocyte haemoglobin equivalent (Ret-He) is routinely measured by modern automated blood analysers and is an early indicator of iron deficiency. The aim of this study was to investigate whether the Ret-He level as calculated by the Sysmex XE-5000 automated blood analyser is a useful parameter for the diagnosis of IDA in a geriatric hospitalized population. MethodsIn a prospective study, blood samples were collected in 26 geriatric patients with IDA and 111 patients with ACD diagnosed according to generally accepted laboratory and clinical criteria. A blood count including Ret-He, mean corpuscular volume (MCV), mean corpuscular haemoglobin (MCH), mean corpuscular haemoglobin concentration (MCHC) and standard iron parameters was performed in each patient. ResultsHaemoglobin, Ret-He, MCV, MCH and MCHC levels were all significantly lower in IDA as compared to ACD patients. However, the area under the curve (AUC) was greater for MCH (0.87, 95% CI 0.78–0.95) and MCHC (0.86, 95% CI 0.76–0.96) then for Ret-He (0.828, 95% CI 0.73–0.93) and MCV (0.80, 95% CI 0.68–0.91). A Ret-He cut-off value of 26pg had a sensitivity and specificity based on its optimal combination of 85% and 69% respectively. ConclusionAnalysis of Ret-He does not perform better than the classical red cell indices such as MCH and MCHC in differentiating IDA and ACD in geriatric patients.

Hepcidin and hemoglobin content parameters in the diagnosis of iron deficiency in rheumatoid arthritis patients with anemia

To explore the utility of the novel iron indices hepcidin, reticulocyte hemoglobin content (Ret-Hgb), and erythrocyte (red blood cell) hemoglobin content (RBC-Hgb) for detection of iron deficiency in rheumatoid arthritis (RA) patients with anemia and active inflammation and to compare these indices with conventional parameters of iron deficiency. Blood samples from 106 outpatients with RA were analyzed in a cross-sectional exploratory study. Forty patients were classified as having either iron deficiency anemia (IDA), anemia of chronic disease (ACD), their combination (IDA/ACD), or "other anemia" based on biochemical parameters for inflammation and iron deficiency. The ability of serum and urine hepcidin, Ret-Hgb, and RBC-Hgb measurement to discriminate among these states was evaluated. Hepcidin content in serum from patients in the IDA group as well as that from patients in the combined IDA/ACD group differed significantly from that in serum from patients in the ACD group. This difference was also observed with hepcidin in urine, Ret-Hgb, and RBC-Hgb, although with less significance. The area under the receiver operating characteristic curve for serum hepcidin was 0.88 for the comparison of IDA/ACD patients with ACD patients and 0.92 for the comparison of the combined IDA group and IDA/ACD group to all other patients with anemia. Hepcidin at <2.4 nmoles/liter had a sensitivity of 89% and a specificity of 88% to distinguish IDA/ACD from ACD. Both Ret-Hgb and RBC-Hgb measurements also allowed differentiation between these latter groups, with a sensitivity of 67% and 89%, respectively, and a specificity of 100% and 75%, respectively. Serum hepcidin and, to a lesser extent, urine hepcidin, Ret-Hgb, and RBC-Hgb, are potential useful indicators for detecting iron deficiency in RA patients with anemia and active inflammation.