Absolute Iron Deficiency Research Articles

Effectiveness and safety of ferric carboxymaltose therapy in peritoneal dialysis patients: an observational study.

BackgroundThe efficacy of intravenous (IV) ferric carboxymaltose (FCM) has been demonstrated in haemodialysis and non-dialysis studies, but evidence is lacking in patients undergoing peritoneal dialysis (PD).MethodsThis multicentre, retrospective study evaluated the effectiveness and safety of FCM in patients on PD over 12 months. We retrospectively reviewed the electronic medical records of PD patients who initiated FCM treatment between 2014 and 2017 across seven Spanish centres.ResultsNinety-one patients were included in the safety population (mean ± SD age 57.7 ± 15.0 years) and 70 in the efficacy population (mean age 50.9 ± 14.5 years). No hypersensitivity reaction, FCM discontinuation or dose adjustment due to a serious adverse event (SAE) was registered in the safety population. The most common non-SAEs reported were headache (four events), mild hypotension (three events) and hypertension (two events), among others. In the efficacy population (n = 70), 68.6% of patients achieved ferritin levels of 200–800 ng/mL, 78.4% achieved transferrin saturation (TSAT) >20%, and 62.8% achieved TSAT >20% and ferritin >200 ng/mL after 12 months of FCM initiation (P < 0.01). Haemoglobin (Hb) levels were maintained at >11 g/dL with a lower dose of darbepoetin throughout the follow-up. The sub-analysis of patients naïve to IV iron and with absolute or relative iron deficiency (n = 51) showed that 76.5% reached ferritin >200 ng/mL, 80.4% TSAT >20% and Hb increased (1.2 g/dL) after 4 months of FCM treatment (P < 0.01).ConclusionIn this multicentre, retrospective, real-world study conducted in the PD population, FCM was effective, safe and easy to administer during routine clinical visits.

Diagnosing Absolute Iron-Deficiency Anemia in Patients on Hemodialysis in a Tertiary Care Centre: A Retrospective Chart Review

Introduction: The gold standard for the diagnosis of absolute iron-deficiency anemia (IDA) in hemodialysis patients is a bone marrow aspirate with iron staining. Many clinicians use peripheral iron indices instead because they are non-invasive. Previous studies suggested that a serum ferritin &lt; 200 ng/mL was a reliable indicator of absolute iron deficiency in the hemodialysis population. However, the sensitivity of serum ferritin for the diagnosis of IDA in hemodialysis patients is poor. Methods: The primary objective of this study was to identify the optimal ferritin value to diagnose patients with absolute iron deficiency, as assessed on bone marrow aspiration, in the renal dialysis population. Secondary endpoints included the rate of clinically relevant findings on gastrointestinal investigation according to iron status. Research Ethics Board approval was obtained from Queen's University for this retrospective chart review. Hematopathology laboratory records were used to determine all individuals who had bone marrow examination at Kingston Health Sciences tertiary referral center between 2008 January 1 and 2018 August 21. This list was cross-referenced with the Nephrology dialysis database to identify the pre-specified study cohort; those who were receiving concurrent hemodialysis or peritoneal dialysis. Iron deficiency was defined as reduced or absent iron stores on bone marrow aspirate with Perl's Prussian blue stain. Anemia was defined as hemoglobin &lt;130 g/L in males and &lt;120 g/L in females. Additional parameters collected included ferritin (normal range 22 - 275 ng/mL male and 4 - 205 ng/mL female), transferrin saturation (TSAT, normal range 20-55%), vitamin B12, folate, albumin, CRP and thyroid function tests. Peripheral iron indices over six months were analyzed; statistical analysis was performed with t-tests and Mann-Whitney U tests. ROC curves were generated to determine the sensitivity and specificity of various threshold values for serum ferritin and TSAT. Results: Between 2008 January 1 and 2018 August 21, 4234 patients underwent bone marrow examination, of whom 28 had received renal dialysis replacement therapy at some point. Fifteen patients concurrently at the time of bone marrow testing receiving hemodialysis form the study population (Table 1). Among these fifteen patients, 6 (40%) were female, median age was 70.5 (range 39 - 80) years and all were anemic (Hb range 73 - 110 g/L). Four of these individuals were absolutely iron-deficient with reduced or absent iron stores by bone marrow evaluation. The mean ferritin and TSAT values for individuals with absolute iron deficiency by bone marrow aspiration was 273.5 ng/mL (n=4; median 224.5 ng/mL; range 158-539 ng/mL) and 22.0% (n=3; median 20%; range 20-26%), respectively. All four commenced erythropoietin stimulating agents; two received oral iron supplementation. Eight patients, including two of those determined to be absolutely iron deficient on bone marrow, had endoscopic investigation. Two were identified to have sources of gastrointestinal bleeding, both with ferritin values in the 100-200 range (106 and 189 ng/mL). With the limited sample size, the sensitivity and specificity of ferritin to identify absolute iron deficiency in this hemodialysis population was 50% and 85%, respectively, at a threshold of 198 ng/mL. Discussion: Ferritin and TSAT are not sensitive markers for absolute iron deficiency in hemodialysis patients. Bone marrow examination is performed in a minority. The small sample size in this study precludes definitive determination of an optimal ferritin cut-off to diagnose iron deficiency in the dialysis population. Uncertainty about actual iron status may result in alternative invasive testing, such as colonoscopy, to investigate the cause of their anemia. Newer tests such as reticulocyte hemoglobin content and percent hypochromic red blood cells are more accurate and may guide diagnosis and management of IDA in hemodialysis patients. However they are not always routinely available. Further studies are needed to compare the utility of these peripheral iron indices to the gold standard bone marrow examination in a larger population, to allow identification of patients with absolute or functional IDA, and minimize invasive and potentially unnecessary investigation. Disclosures Hay: AbbVie: Research Funding; Kite: Research Funding; Janssen: Research Funding; Seattle Genetics: Research Funding; Celgene: Research Funding; MorphoSys: Research Funding; Roche: Research Funding; Novartis: Research Funding; Gilead: Research Funding; Takeda: Research Funding.

Is anemia a clinical marker of NSAIDs-induced upper gastrointestinal lesions in patients with spondyloarthritis?

Background: Anemia is a frequent comorbid conditions in patients with spondyloarthritis (SpA). Its development is associated with the activity of the underlying disorder, and in some cases can be a complication of medical treatment. Investigation into the particulars of the anemia, its prevalence in SpA patients is of considerable interest due to the long-term inflammatory process, on the one hand, and high frequency of non-steroidal anti-inflammatory drugs (NSAIDs) usage, on the other.Aim: To assess the incidence of NSAID-induced lesions of upper gastrointestinal tract in patients with SpA and anemia.Materials and methods: This cross-sectional observational study included 107 patients with proven SpA (mean age, 44 [36; 53] years; SpA duration, 16 [9; 21] years; men, 61.9%) who were treated in the Department of Rheumatology, Saratov Regional Clinical Hospital, from 2017 to 2018. We assessed their blood cell counts, C-reactive protein levels, iron kinetic parameters (serum iron, transferrin, ferritin, transferrin saturation). Anemia was diagnosed according to the World Health Organization criteria. Two groups were formed depending on the presence of absolute iron deficiency: group 1, 13 patients with anemia of chronic disease (ACD), group 2, 3 patients with iron deficiency anemia (IDA) and 26 patients with ACD + IDA. Esophagogastroduodenoscopy (EGDS) was performed to assess mucous membranes of the upper gastrointestinal tract in patients with anemia.Results: Anemia was found in 42 (39.3%) patients, 38 (90.5%) of them had mild anemia. The increase in the activity of the underlying disorder judged by changes in the laboratory markers of systemic inflammation (erythrocyte sedimentation rate and C-reactive protein levels) significantly correlated with a decrease in hemoglobin concentration (r = -0.5715 and r = -0.3498 respectively, p&lt;0.05). At EGDS, NSAIDs-induced erosions in the esophagus and/or stomach were found detected in 1 (7.7%) patient of the group 1 and in 1 (3.4%) patient of the group 2. A past episode of NSAIDs-induced erosions in the stomach and duodenum was noted in 4 (13.8%) patients of the group 2, whereas at the time of the study no mucous membranes defects were found at EGDS.Conclusion: Anemia was found in more than one third of SpA patients, with 29 of them (69%) having laboratory signs of iron deficiency, but only 1 (3.4%) patient had NSAIDs-induced gastropathy confirmed at EGDS. NSAIDs-associated enteropathy could be the cause of iron deficiency in these patients that would require additional patient examination. The development of iron deficiency can be pathophysiologically associated to prolonged inhibition of alimentary iron absorption against the background of persistent systemic inflammation and depletion of the iron pool in the absence of gastrointestinal blood losses.

Evaluation of Iron Status in Patients of Solid Organ Malignancies: Study from a Cancer Research Centre.

Anemia associated with cancer is a major public health issue. The gravity of this problem is likely to be higher in India due to already existing malnutrition in the general population. Iron deficiency anemia (IDA) as a subset has not been evaluated in Indian population of cancer patients. This study was undertaken to evaluate iron status among newly diagnosed advanced-stage cancer patients with anemia at a cancer research institute in India. Sixty-four patients of anemia were identified who fulfilled the inclusion criteria. Iron status was noted. Absolute iron deficiency (AID) was identified in 8 (12.5%) patients. Functional iron deficiency (FID) was seen in 48 (75%) patients. Probable functional iron deficiency (PFID) was seen in 2 (3.1%) patients while no iron deficiency (NID) was seen in 6 (9.3%) patients. FID is seen in majority of advanced-stage solid organ cancer patients in India. Large sample studies are required to better define the exact prevalence of iron deficiency, chemotherapy-induced anemia, and anemia in cancer subtypes.

Iron deficiency in children at the time of initial neuroblastoma diagnosis.

ABSTRACTImportanceThere is a high incidence of iron deficiency in children worldwide. Notably, however, while iron deficiency is the most common cause of anemia, little is known about the prevalence and different types of iron deficiency in neuroblastoma patients.ObjectiveThe aim of the present study was to investigate the prevalence of iron deficiency in patients newly diagnosed with neuroblastoma.MethodsA total of 195 newly diagnosed neuroblastoma patients from November 2015 to January 2018 were analyzed retrospectively. The survival analysis was estimated by the Kaplan‐Meier method.ResultsOf the 195 neuroblastoma patients included in the study, 121 (62.1%) had iron deficiency, 55 (28.2%) had absolute iron deficiency, and 66 (33.9%) had functional iron deficiency. Being aged ≥ 18 months, tumor originating in the abdomen, International Neuroblastoma Risk Group Staging System M, high‐risk neuroblastoma, lactate dehydrogenase ≥ 1500 U/L, neuron‐specific enolase ≥ 100 U/L, unfavorable histologic category, MYCN amplification, chromosome 1p loss, and bone marrow metastasis were associated with significantly higher rates of functional iron deficiency (P < 0.05).InterpretationFunctional iron deficiency at the time of initial neuroblastoma diagnosis predicted lower event‐free survival. Long‐term effects of iron supplementation in neuroblastoma patients with different types of iron deficiency need to be further studied.

Prevalence, correlates and outcomes of absolute and functional iron deficiency anemia in nondialysis-dependent chronic kidney disease.

Anemia is associated with adverse outcomes in those with chronic kidney disease (CKD). We examined the association of absolute and functional iron deficiency anemia (IDA) with adverse outcomes (cardiovascular hospitalization, dialysis and mortality) in those with nondialysis-dependent CKD. Nondialysis-dependent CKD patients followed in the US Veterans Administration with hemoglobin level measured within 90 days of the date of the second estimated glomerular filtration rate <60 mL/min/1.73 m2 were included. Logistic regression, multivariate Cox proportional hazards and Poisson regression models adjusted for demographics and comorbidities were used to assess the prevalence and correlates of absolute [transferrin saturation (TSAT) ≤20%, ferritin <100ng/mL] and functional (TSA T≤20%, ferritin >100-500 ng/mL) IDA and the associations of absolute and functional IDA with mortality, dialysis and cardiovascular hospitalization. Of 933 463 patients with CKD, 20.6% had anemia. Among those with anemia, 23.6% of patients had both TSAT and ferritin level measured, of whom 30% had absolute IDA and 19% had functional IDA. Absolute IDA in CKD was not associated with an increased risk of mortality or dialysis but was associated with a higher risk of 1-year {risk ratio [RR] 1.20 [95% confidence interval (CI) 1.12-1.28]} and 2-year cardiovascular hospitalization [RR 1.11 (95% CI 1.05-1.17)]. CKD patients with functional IDA had a higher risk of mortality [hazard ratio (HR) 1.11 (95% CI 1.07-1.14)] along with a higher risk of 1-year [RR 1.21 (95% CI 1.1-1.30)] and 2-year cardiovascular hospitalization [RR 1.13 (95% CI 1.07-1.21)]. Ferritin >500 ng/mL (treated as a separate category) was only associated with an increased risk of mortality [HR 1.38 (95% CI 1.26-1.51)]. In a large population of CKD patients with anemia, absolute and functional IDA were associated with various clinical covariates. Functional IDA was associated with an increased risk of mortality and cardiovascular hospitalization, but absolute IDA was associated only with a higher risk of hospitalization.

Modern ferrokinetics metabolites in the diagnostics of anemic in patients with disseminated stages of Hodgkin's lymphoma when conducting intensive chemotherapy.

Evaluation of anemic syndrome (AS) was performed in 79 patients with advanced stages of Hodgkin's lymphoma (LH) at various stages of chemotherapy (CT) according to the EACOPP-14 scheme. Against the background of the treatment, the number of erythrocytes and, accordingly, the HCT indices decreased with each subsequent cycle of chemotherapy (CTC) and reached the maximum reduction to 5, 6 th CCT. Absolute iron deficiency (IDA), which was combined with a low level of EPO and an inadequate degree of anemia, was found in a few LH patients (5 people, 6.3%). Functional iron deficiency (FDZH) was diagnosed in 9 patients (11.4%), had the same morphological signs as IDA. Namely, microcytosis, erythrocyte hypochromia and low hemoglobin content in reticulocytes (RET-HE). In contrast to IDA, patients with FDZh concentration of FR, GP-25 and IL-6 were high. Despite the fairly large reserves of iron, the level of rRTF testified to the "iron hunger" of the erythrocariocytes of the bone marrow, its index exceeded the upper limit of the norm, while RET-HE was low. In 34 (43%) patients, LH revealed a deficiency of endogenous erythropoietin (EPO), which was observed not only in patients with AHZ, but also in patients with IDA. Lower levels of EPO were detected in patients with leukopenia and very low erythropoietic activity of the bone marrow.

Establishing Absolute Iron Deficiency Anaemia before Referring Patients to Colorectal Fast Track Clinics Can Help to Increase the Diagnostic Yield of the Bowel Cancer Screening Programme

Establishing Absolute Iron Deficiency Anaemia before Referring Patients to Colorectal Fast Track Clinics Can Help to Increase the Diagnostic Yield of the Bowel Cancer Screening Programme

1814P - The use of intravenous ferric carboxymaltose without erythropoiesis-stimulating agents in the treatment of anemia in cancer patients undergoing chemotherapy with or without radiotherapy

BackgroundAnemia in cancer patients undergoing chemotherapy is commonly encountered and may worsen their quality of life. Because of recent concerns about their negative effect on overall survival and serious adverse events, erythropoiesis-stimulating agents (ESA) are not commonly prescribed. This study will assess the efficacy and safety of intravenous ferric carboxymaltose (FCM) therapy in such patients. MethodsAdult patients with non-myeloid malignancies on chemotherapy with Hemoglobin (Hb)≤ 11.0g/dL and a life expectancy >24 weeks were recruited. Based on serum ferritin (sFr) level and transferrin saturation (TSAT), patients were categorized into three Groups: Group-I (Absolute Iron Deficiency: AIDA) with sFr <30ng/mL and TSAT <20%. Group-II (Functional Iron Deficiency Anemia: FIDA) with sFr 30-800ng/mL and TSAT <20%. Patients with TSAT >20% were placed in group-III as “others”. Based on Hb level and body weight, patients were given FCM in one or two short intravenous infusions. ResultsA total of 84 patients; 70 (83.3%) females were recruited. Median age [standard deviation] was 53.8 [10.6] years. Chemotherapy varied according to the primary cancer and many had it as a second-line or beyond. The median Hb level at baseline was 10.2 (range: 8.3-11.0 ) gm/dL. At week-12, patients with AIDA (26,31.0%) and FIDA (24, 28.6%) had a significant increment in Hb (median increment: 2.35 and 1.5gm/dL, respectively). Patients in Group-III (34, 40.5%) had limited response. Most of the increment (≥1.0g/dL) occurred as early as week-3. No immediate infusion-related adverse events were reported. However, asymptomatic hypophosphatemia was observed in 39 (46.4%) patients (table).Table1814PTableVariablesAbsolute iron deficiency (n=26)Functional iron deficiency (n=24)Others (n=34)P-valueFerritin Level (week 12, mg/mL) Mean (SD) Median (range)589 (509) 442 (177-2794)838 (875) 577 (168-4184)956 (667) 802 (166-2687)0.0247Phophorus level (week 2, mg/dL) Mean (SD) Median (range)1.8 (0.7) 1.5 (1.1-3.4)2.5 (1.0) 3.3 (1.0-5.4)2.2 (0.9) 3.3 (1.0-4.1)0.0124Hypophophatemia Number Percentage17 65.4%6 25.0%16 47.1% ConclusionsIntravenous FCM, without ESA, is safe and effective in the treatment of anemia in cancer patients undergoing active treatment with chemotherapy. Legal entity responsible for the studyThe authors. FundingKing Hussein Cancer Center. DisclosureAll authors have declared no conflicts of interest.

P6226Association of functional iron deficiency with incident cardiovascular diseases and mortality in the general population

Abstract Background Functional iron deficiency (FID) has been established as a risk factor in patients with cardiovascular diseases (CVD). As opposed to absolute iron deficiency, it reflects stored iron as well as utilized iron and allows for a more accurate evaluation of individual iron status. However, evidence is scant on the relevance of FID to the incidence of CVD in the general population. Aim This study aimed to evaluate the association of FID with incident cardiovascular diseases and mortality endpoints in a large population-based cohort. Methods FID was defined as either ferritin below 100 μg/L or ferritin between 100 and 299 μg/L and transferrin saturation below 20%. Only individuals free of CVD at baseline from three population-based European cohorts were included. Multivariable-adjusted sex- and cohort-stratified Cox regression analyses were performed to evaluate the association of functional iron deficiency with incident cardiovascular diseases (coronary heart disease, cerebral infarction, heart failure and atrial fibrillation) as well as with all-cause and cardiovascular mortality. Adjustments were performed for sex (as strata), age (as time scale), smoking, total cholesterol, systolic blood pressure, diabetes, body mass index and high-sensitive C-reactive protein. Results In total, N=12146 individuals were included in the analysis with a median age of 59.0 years (25thpercentile 45.0, 75thpercentile 68.0), and 45.2% men. Incidence of FID was 64.3%. Median follow-up times were 12.3 to 21.8 years, with an all-cause mortality rate of 18.2% and a cardiovascular mortality rate of 6.2%. Incident coronary heart disease, cerebral infarction, heart failure and atrial fibrillation were observed in 8.7%, 6.5%, 5.9% and 11.7%, respectively. FID was significantly associated with all-cause mortality (hazard ratio (HR) 1.12, 95% confidence interval (CI) 1.01–1.24, p=0.034), cardiovascular death (HR 1.26, 95% CI 1.03–1.54, p=0.027) and incident coronary heart disease (HR 1.23, 95% CI 1.06–1.43, p&lt;0.01). There was no significant association with the other tested endpoints. Conclusion In our analysis of population-based cohorts, FID showed a significant positive association with all-cause as well as cardiovascular mortality and incident coronary heart disease. Further research is needed to validate the role of FID as a cardiovascular risk factor in the general population and to evaluate the impact of iron supplementation on gender and outcome.

ПОРІВНЯЛЬНА ХАРАКТЕРИСТИКА ПОКАЗНИКІВ ЯКОСТІ ЖИТТЯ У ПАЦІЄНТІВ З ХРОНІЧНОЮ СЕРЦЕВОЮ НЕДОСТАТНІСТЮ ЗІ ЗНИЖЕНОЮ ФРАКЦІЄЮ ВИКИДУ ЛІВОГО ШЛУНОЧКА ЗАЛЕЖНО ВІД ВАРІАНТУ ЗАЛІЗОДЕФІЦИТУ

Introduction. Quality of life (QoL) indicators in case of chronic heart failure (CHF) are associated with a number of clinical and instrumental indicators, which makes it possible to consider its assessment as one of the leading indicators of its severity. From a practical point of view, the identification of QoL indicators as the markers of CHF severity in patients with concomitant iron metabolism disorders, including different variants of latent and manifest iron deficiency (ID)is rather interesting. Purpose. To compare QoL parameters by means of MOS SF-36 and MLHFQ questionnaires in patients with CHF with reduced left ventricular ejection fraction with different iron deficiency types. Materials and Methods. 152 patients with CHF functional class (FC) II-III according to NYHA with reduced left ventricular (LV) ejection fraction (EF) of hypertensive and ischemic etiology with/and without iron deficiency (ID) were examined. All patients were divided into three clinical groups: the first clinical group (which is presented as a comparison group) amounted to 30 (19.7 %) patients with CHF with reduced LV EF without ID, the second one amounted to 60 (39.5 %) patients with CHF with reduced LV EF and latent ID, which included a number of patients with functional and absolute ID and the third clinical group amounted to 62 (40.79 %) patients with I-II severity degree of concomitant iron deficiency anemia (IDA). In order to assess QoL, all patients were interviewed using MOS SF-36 and MLHFQ. The comparison of the obtained findings was carried out among groups of patients with CHF with reduced LV EF without iron metabolism disorders, with functional ID and absolute ID, and among groups of patients with CHF with reduced LV EF without iron metabolism disorders, with I degree of IDA and II degree of IDA. Research findings. It was detected that in comparison with the group of patients without ID, QoL indicators according to MLHFQ questionnaire in patients with functional ID and absolute ID were significantly worse – 49.5 versus 53.5 (p = 0.05) and 60 points (p = 0.009), respectively. Physical health (PH) in these groups was 37.9 (p = 0.033) and 37.2 (p = 0.0068), respectively, which significantly differed from PH value in the comparison group – 41.2 points. In patients with functional ID and absolute ID lower PH values were detected due to significantly worse indicators of physical functioning (PF), role-physical functioning (RP) resulting from physical condition and general health (GH). Similar results were obtained during the analysis of QoL in patients with IDA of different degrees. In patients with mild IDA and moderate IDA as compared to the group of patients without ID, QoL indicators, according to MLHFQ questionnaire, were significantly worse (p = 0.007) and (p < 0.00001) 57 and 62 versus 49.5 points, respectively. In addition, it was detected that PH value according to SF-36 questionnaire results in the groups with IDA was also significantly lower than PH value in the group without ID due to low values of PF, RP and GH and amounted to 36.8 (p = 0.01) and 33.6 (p < 0.00001) versus 41.2 points, respectively. According to the conducted analysis, mental health (MH) decreased with the presence of functional and absolute ID and with an increase of IDA from mild to moderate degree, however significantly lower value was detected only in the group with moderate IDA as compared to the group of patients without ID (p = 0.02). In addition, a number of significant relations between QoL indicators according to MLHFQ, PH and MH scale SF-36 and hematological parameters and a number of iron metabolism indicators were detected during the study. This confirms the dependence of the patients’ QoL on existing iron metabolism disorders. Conclusions. Patients with CHF with reduced left ventricular ejection fraction and concomitant ID, regardless of the presence of anemia, are characterized by the worse QoL level as compared to the patient without ID. Whereas, latent functional and absolute ID has the same clinical relevance in terms of deterioration of QoL of patients with CHF. Reduction of iron metabolism levels can be considered as predictors of deterioration of patients' QoL and severe CHF.

Prevalence of anemia and compliance to the National Comprehensive Cancer Network guidelines for workup and treatment of anemia among patients with gynecologic malignancies.

32 Background: The National Comprehensive Cancer Network (NCCN) recommends prompt evaluation of anemic patients with hemoglobin (Hb) ≤ 11g/dL. There are a paucity of studies evaluating compliance with the NCCN guidelines. Our objective was to investigate the prevalence of anemia among patients diagnosed with gynecologic cancers and assess compliance with NCCN guidelines. Methods: We performed a retrospective cohort study of patients diagnosed and treated with gynecologic cancer at our institution from 2008-2018. Tumor-registry-confirmed cancer cases were identified using ICD codes from the Synthetic Derivative (SD) database which is a de-identified copy of our institution’s electronic medical record. Patients were included if they were between the ages of 18 and 89, had their initial care at our institution, and had a Hb within the first 6 months of diagnosis. Dual primaries were excluded. Anemia was defined as Hb ≤ 11g/dL. Anemia was graded using the CTCAE v.4.0. Absolute and possible iron deficiency were defined by NCCN Guidelines. Results: We identified 1031 patients who met our inclusion criteria. The median age was 61 years (range 20 - 86). The most common malignancy was uterine cancer 509 (49%) followed by ovarian 262 (25%), cervical 133 (13%), vulvar 107 (10%) and vaginal 20 (2%). Of the 1031 patients in our study, 662 (64%) were noted to be anemic within six months of diagnosis. Of these patients 128 (19%) were noted to have grade 1, 309 (47%) grade 2, and 225 (34%) grade 3 anemia. Of those who were anemic, 90 (14%) underwent any workup for anemia, of which 63 (10%) had iron studies performed. Of those with iron studies performed, 7 (1%) patients had absolute iron deficiency and 24 (4%) had possible iron deficiency. Despite the small percentage of individuals with anemia evaluation, 266 (34%) patients received treatment of anemia. Treatments included: oral iron 47 (7%), IV iron 6 (1%), and blood transfusion 213 (32%). Conclusions: Anemia is pervasive among gynecologic cancer patients, but compliance with NCCN guidelines is low. Our data suggest there are opportunities for improvement in evaluation and management of anemia among gynecologic cancers.

Is iron deficiency involved in the pathogenesis of chronic inflammatory skin disorders?

Iron is an essential microelement in the human body due to its role in hematopoiesis, involvement in energetic processes, synthesis and decomposition of lipids, proteins and nuclear acids. Iron deficiency (ID) is common in healthy populations and also frequently coincides with natural course of chronic diseases. The former is typically present when the overall iron body storages are exhausted (absolute ID), most often due to insufficient iron supply, malabsorption or increased blood loss and coincides with anemia. The latter is a result of defected iron metabolism and reflects a condition, when despite adequate iron stores in the body, iron itself is trapped in the reticuloendothelial system, becoming unavailable for the metabolic processes. It typically occurs in the presence proinflammtory activation in chronic conditions such as chronic kidney disease, inflammatory bowel disorders, malignancies and heart failure. To date there are very few publications concerning the potential role of ID in chronic dermatological disorders. We have recently found that patients with psoriasis demonstrate pattern of ID which can be characterized by negative tissue iron balance with depleted iron stores in the body. Interestingly, presence of ID was not related to the severity of psoriasis, but rather determined by patients low body mass index. We are currently investigating the hypothesis that derangements in iron metabolism resulting in ID can be also present in hidradenitis suppurativa – the other chronic dermatologic disease associated with inflammatory and autoimmune activation.

Iron deficiency during first-line chemotherapy in metastatic cancers: a prospective epidemiological study.

Anemia is common in oncology and negatively impacts quality of life. However, there is lack of knowledge about iron deficiency (ID) epidemiology. The aim of this study was to prospectively assess iron status in patients with locally advanced or metastatic cancer beginning chemotherapy. In this prospective, multicenter cohort study, anemia and ID were evaluated in patients with locally advanced or metastatic solid tumors and lymphoma before starting chemotherapy. Blood samples were collected at inclusion (W0), 6weeks (W6), and 12weeks (W12). Prevalence was evaluated in the general population, according to tumor location and was correlated with tumor response. One hundred twenty-nine patients were enrolled between 2013 and 2015; 119 had solid tumors and 10 lymphomas. At W0, there were no significant difference between locations with a prevalence around 50-60% (range 47.2-70.4%) and only a trend for colorectal cancer (70.4%, P = 0.069) due to a higher prevalence of absolute ID (18.5%). Prevalence of ID+ decreased between W0 and W6 and remained stable until W12 due to the proportion of patients with ID and without anemia. However, anemia prevalence increased during W0 and W6 and remained stable to W6 from W12 due to patients with anemia but without ID. A significant correlation between tumor response and ID prevalence was found (P = 0.036). We confirm the high prevalence of ID and anemia in cancer patients. ID status is correlated to tumor response providing a strong rationale for iron monitoring during cancer management.

The Relationship between Nutritional Status, Anemia and Other Vitamin Deficiencies in the Elderly Receiving Home Care.

The aim of this study was to evaluate the prevalence of anemia and other vitamin deficiencies among elderly home care patients and to evaluate the causes of anemia and effect of malnutrition as a contributing factor. Anemia was defined according to the World Health Organization. Hemogram, serum iron, iron binding capacity, ferritin and transferrin saturation values, serum vitamin B12, folic acid and vitamin D levels were evaluated. It was tried to differentiate as absolute iron deficiency anemia, anemia of chronic disease, anemia of unknown cause and vitamin B12 deficiency anemia. Malnutrition was evaluated by Mini Nutritional Assessment test. Total of 472 patients (mean age 81,4±7,4 years) were included in the study. Anemia was detected in 179 (%37,9) patients, 22,7% of males and 45,5 % of female. Prevalence of iron deficiency anemia, vitamin B12, folic acid and vitamin D deficiencies were found 43%, 46%, 19% and 91% respectively. 22,8% of all patients were malnourished, 17,5% were under malnutrition risk. In patients with anemia 16,2% chronic disease anemia and 37,4% unknown anemia were detected. With or without malnutrition, iron deficiency anemia, vitamin B12 deficiency and vitamin D deficiency were common in the home care elderly patients.

Mechanisms, mishaps and manipulation of iron uptake

Mechanisms, mishaps and manipulation of iron uptake

Assessment of iron-restricted erythropoiesis in chronic renal disease: evaluation of Abbott CELL-DYN Sapphire mean reticulocyte hemoglobin content (MCHr)

We studied the performance of mean reticulocyte hemoglobin content (MCHr), measured on Abbott CELL-DYN Sapphire analyzer for the detection of functional iron deficiency. Patients with anemia and with renal disease were prospectively selected from the outpatient population of our hospital, 512 subjects were studied. Diagnoses and other medical data were retrieved from the hospital information system. MCHr was measured using a CELL-DYN Sapphire hematology analyzer (Abbott Diagnostics). Standard laboratory and statistical tests were used. Receiver operating characteristic (ROC) analysis was used to establish the diagnostic performance of MCHr for detecting iron-restricted erythropoiesis, with transferrin saturation <20% as the gold standard. Patients in the iron deficiency anemia group all had a state of iron depletion and iron-restricted erythropoiesis (median MCHr 25.4 pg). Patients with anemia of chronic disease showed also low MCHr, median 27.6 pg, but not statistically different from the iron deficient group (p = .0585). Renal patients with iron restriction (n = 66) had significantly lower MCHr (p < .0001) than those receiving adequate iron supply (n = 100): median MCHr were 27.9 and 32.5 pg, respectively. ROC analysis gave sensitivity 84.4% and specificity 80.1% with area under curve 0.863 (95% CI 0.823–0.902) at an MCHr cut-off 30.0 pg. MCHr on CELL-DYN Sapphire has equivalent clinical performance for detecting absolute or functional iron deficiency in patients with chronic kidney disease as previously published for another type of analyzer.

Protocol and baseline data for a prospective open-label explorative randomized single-center comparative study to determine the effects of various intravenous iron preparations on markers of oxidative stress and kidney injury in chronic kidney disease (IRON-CKD)

BackgroundIntravenous (IV) iron is frequently used to treat iron deficiency/anemia in patients who are unable to tolerate oral iron or the oral iron is not sufficient toreplete iron requirements. However, safety concerns regarding the potential increase in oxidative stress and other adverse effects persist and it remains unclear whether all iron preparations are equivalent. Indeed, the comparative risk of adverse events with IV iron preparations has not been extensively assessed.We hypothesize that IV iron leads to changes in oxidative stress, endothelial function, and potential renal damage depending on the iron formulation (related to the generation of “free” or catalytic labile iron) and this may result in more tubular and glomerular injury manifested as increased proteinuria and raised neutrophil gelatinase–associated lipocalin (NGAL) levels in patients with chronic kidney disease (CKD).MethodsIRON-CKD is a prospective, open-label, explorative, randomized, single-center study designed to compare the safety and efficacy of three parenteral iron preparations: low-molecular-weight iron dextran–Cosmofer, iron sucrose–Venofer, and iron isomaltoside–Monofer. The study includes 40 adults who have established CKD stages 3–5 and serum ferritin (SF) of less than 200 μg/L or transferrin saturation (TS) of less than 20% (or both); they were randomly assigned in a 1:1:1:1 ratio to 200 mg iron dextran, 200 mg iron sucrose, 200 mg iron isomaltoside, or 1000 mg iron isomaltoside. After randomization, participants undergo baseline assessments and then an iron infusion. Each participant is followed up at 2 h, day 1, week 1, and months 1 and 3. At each follow-up visit, patients undergo clinical review, measurement of pulse wave velocity (PWV), blood tests for renal function, and collection of serum/plasma samples for oxidative stress and inflammatory markers.The primary outcomes are measures of oxidative stress, inflammatory markers, and markers of acute renal injury in comparison with baseline measures of each iron preparation and between each of the iron preparations. Secondary objectives include effects on hematinic profiles and hemoglobin concentrations, changes in arterial stiffness, incidence of significant side effects, and change in patients’ quality of life.ResultsBetween October 2015 and April 2018, 521 individuals were identified as potential participants; 216 were contacted, 56 expressed an interest, 49 attended a screening visit, and 40 were confirmed to meet the eligibility criteria and were randomly assigned. The mean age was 58.3 (standard error of the mean 4.4) years, and 23 (58%) were male. All patients were white and English-speaking. The mean SF was 66.6 μg/L, TS was 21.2%, and hemoglobin was 121.6 g/L at randomization for the whole group. The mean estimated glomerular filtration rate was 27.8 mL/min, the urinary protein/creatinine ratio was 104.3 mg/mmol, and CRP was 6.65 mg/L.DiscussionIRON-CKD will provide important information on the short-term effects of three preparations of IV iron in CKD patients with biochemical functional or absolute iron deficiency on measures of oxidative stress, inflammation, endothelial function, and renal injury.Trial registrationEuropean Clinical Trials Database (EudraCT) number 2010-020452-64.

Etiological spectrum of anemia in non-dialysis-dependent chronic kidney disease: A single-center study from India.

A retrospective study was conducted over seven years and it aimed to find out various causes of anemia among patients with chronic kidney disease (CKD). The study included nondialysis-dependent adult CKD patients who underwent anemia evaluation. A total of 584 patients were studied. Three hundred and twenty-one (55%) patients were male and 263 (45%) were female. The mean age of the patients was 55.5 ± 14 years. One hundred and seventy-eight (30.5%) had a diabetic CKD and 406 (69.5%) had a nondiabetic CKD. Seventy-two (12.3%) patients were in CKD Stage 3, 193 (33%) patients in CKD Stage 4, and 319 (54.6%) patients in CKD Stage 5. The mean hemoglobin was 9.2 ± 2.2 g/dL. There was a progressive fall in hemoglobin with increasing severity of CKD and in CKD Stage 3, 4, and 5 the mean hemoglobin was 10 ± 2.2, 9.4 ± 2.1, and 8.4 ± 1.9 g/dL, respectively (P = 0.001). Most (47.4%) patients had moderate anemia followed by anemia of mild (31.4%) and severe (21.4%) degrees. Three hundred and seven (52.6%) patients had percent transferrin saturation (TSAT) <20% (functional iron deficiency). One hundred and sixty-two (27.7%) patients had serum ferritin <100 ng/mL (absolute iron deficiency); 334 (57.2%) patients had serum ferritin 100-500 ng/mL, but in 175 (52.4%) of them, TSAT was <20%; 88 (15.1%) patients had serum ferritin >500 ng/mL (58 (65.6%) were C-reactive protein (CRP) + and 55 (62.5%) had TSAT <20%). Overall, 392 (67.1%) patients had functional or absolute iron deficiency. One-third of the patients had elevated CRP levels. The anemia was macrocytic in 20.4% suggesting deficiency of folic acid and/or Vitamin B12. A high proportion (74.6%) of patients with normocytic anemia had iron deficiency. In the majority of nondialysis-dependent CKD patients, the etiology of anemia may be multifactorial; therefore, the treatment should be determined by documented causes of anemia.

Association of hepcidin and anemia in early chronic kidney disease.

Hepcidin is being extensively studied for anemia and inflammation in chronic kidney disease (CKD) patients. Hepcidin is thought to regulate iron metabolism by iron blockade through various mechanisms. Patients with CKD have early cardiac mortality due to anemia and subclinical inflammation; hence, we studied hepcidin as a biomarker in patients with early stage of CKD in relation to anemia and inflammation. In our cross-sectional study, a total of 80 patients were enrolled of whom, there were 25, 26, and 29 patients in CKD stages 1, 2, and 3, respectively. Patients were divided into normal iron level (39), functional iron deficiency (FID) (18), and absolute iron deficiency (AID) (23) based on transferrin saturation and ferritin. We found significantly high level of hepcidin (P <0.05) and high-sensitivity C-reactive protein (hsCRP) (P <0.05) in FID as compared to AID as well as normal iron level. We also found other inflammatory markers such as albumin, transferrin, and ferritin to be significantly associated with FID. In univariate analysis, hemoglobin (Hb) varied significantly with serum total iron-binding capacity (r = 0.40, P <0.001), log hsCRP (r = -0.32, P <0.01), and log ferritin (r = -0.23, P <0.05); however, Hb was not affected significantly with log hepcidin (r = -0.07, P >0.05). The study indicates that among early CKD patients with FID, there was high level of hepcidin along with other inflammatory parameters, which may be associated with poor cardiovascular disease outcome due to increased inflammation.